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BACKGROUND & AIMS: The circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality. METHODS: This prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005-2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity. RESULTS: The median (interquartile range) of 25(OH)D level was 55.8 (40.8-71.8) nmol/L. During a median follow-up of 14.3 years, 2250 deaths were recorded. Compared with participants with a 25(OH)D level <30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥75 nmol/L) were associated with a lower risk of all-cause mortality: HR (95% CI) of 0.82 (0.69-0.98), 0.74 (0.62-0.88), and 0.69 (0.57-0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI: 0.39-0.77) for a 25(OH)D level ≥75 nmol/L compared with <30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men. CONCLUSIONS: Vitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50-60 nmol/L may contribute to longevity and warrants further investigation.
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Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD.
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Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1ß). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer's symptoms as LPS treatment enhances level of amyloid beta (Aß), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aß, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer's properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD.
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OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that comprises amyloid-beta protein (Aß) as a main component of neuritic plaques. Its deposition is considered a trigger for AD pathogenesis, progression, and the clinical symptoms of cognitive impairment. Some distinct pathological features of AD include phosphorylation of tau protein, oxidative stress, and mitochondrial dysfunction. These pathological consequences tend to produce reactive oxygen species (ROS), resulting in the dysregulation of various signaling pathways of neuroinflammation and neurodegeneration. The relationship between the Aß cascade and oxidative stress in AD pathogenesis is like a "chicken and egg" story, with the etiology of the disease regarding these two factors remaining a question of "which comes first." However, in this review, we have tried our best to clarify the interconnection between these two mechanisms and to show the precise cause-and-effect relationship. Based on the above hallmarks of AD, several therapeutic strategies using natural antioxidants, monoclonal antibodies, and vaccines are employed as anti-Aß therapy to decrease ROS, Aß burden, chronic neuroinflammation, and synaptic failure. These natural antioxidants and immunotherapeutics have demonstrated significant neuroprotective effects and symptomatic relief in various in vitro and in vivo models, as well as in clinical trials for AD. However, none of them have received final approval to enter the drug market for mitigating AD. In this review, we extensively elaborate on the pitfalls, assurances, and important crosstalk between oxidative stress and Aß concerning current anti-Aß therapy. Additionally, we discuss future strategies for the development of more Aß-targeted approaches and the optimization of AD treatment and mitigation.
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Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.
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Introduction: Hypertension is a primary risk factor for cardiovascular disease and all-cause mortality. This study investigated sex-based differences in the association between the risk of hypertension and resistance training (RT) levels, including training frequency and period. Methods: We enrolled 162,102 participants from nationwide Korean cohorts. The training period (months) and frequency (per week) of RT were used to investigate the presence of an inverse dose-response relationship between RT levels and the risk of hypertension. Multiple logistic regression models were used to evaluate the risk of hypertension in relation to RT levels. Results: The prevalence of hypertension in the study population was 36.28% in men and 26.94% in women. Performing RT was associated with an 8% reduction in the risk of hypertension in women but not in men. In women, performing RT for 3-4 days/week, compared with not performing RT, reduced the risk of hypertension by 11%, even after adjusting for covariates, including RT time per week and period. However, in men, no significant association was observed between training frequency and the risk of hypertension. We also evaluated the risk of hypertension by simultaneously considering both the RT frequency and period. Performing RT for 3-4 days/week and ≥5 days/week were markedly related to 14 and 11% hypertension risk reduction, respectively, in women who had been performing RT for at least 6 months. Conclusion: Given that no inverse dose-response association was observed between RT frequency and hypertension risk, engaging in RT for 3-4 days/week for at least 6 months is recommended for women. Further longitudinal studies are needed to verify sex-based differences in the antihypertensive effects of regular RT.
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Hipertensão , Treinamento Resistido , Humanos , Hipertensão/epidemiologia , Masculino , Feminino , República da Coreia/epidemiologia , Fatores Sexuais , Pessoa de Meia-Idade , Treinamento Resistido/estatística & dados numéricos , Adulto , Fatores de Risco , PrevalênciaRESUMO
Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1ß to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1ß, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1ß-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.
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BACKGROUND: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. MATERIALS AND METHODS: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. RESULTS: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52-2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50-2.65), 2.12 (1.66-2.58), and 1.75 (1.17-2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55-19.44 %] of the relationship between OAB and cognitive impairment. CONCLUSIONS: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.
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Disfunção Cognitiva , Bexiga Urinária Hiperativa , Humanos , Feminino , Bexiga Urinária Hiperativa/epidemiologia , Bexiga Urinária Hiperativa/complicações , Estudos Transversais , Pessoa de Meia-Idade , Disfunção Cognitiva/epidemiologia , Prevalência , Inquéritos e Questionários , Noctúria/epidemiologia , Qualidade do Sono , Modelos Logísticos , AdultoRESUMO
The Korea Nurses' Health Study (KNHS) is an ongoing, large-scale, prospective cohort study of women nurses, focusing on the effects of occupational, environmental, and lifestyle factors on the health of women. The first KNHS survey was performed in 2013-2014 (n=20,613). As of December 2023, 11 follow-up surveys have been conducted. Participants who were pregnant were asked to participate in the early pregnancy survey (n=2,179) and postpartum survey after giving birth (n=2,790). The main variables included socio-demographic, work-related, lifestyle, physical, mental, and women's health factors. Blood, urine, and toenail samples were collected from a participant subgroup of the first survey (n=1,983). The subgroups of the second survey completed a food frequency questionnaire in 2019 (n=300) and 2021 (n=871). In 2020, a subgroup of the first survey answered a coronavirus disease 2019-related survey (n=975). To examine various health-related factors in young adults, new participants were added to the KNHS cohort in the 11th (n=1,000) and 12th (n=1,002) surveys. The KNHS cohort will help identify health and illness determinants in Korean women. Data can be accessed at https://coda.nih.go.kr/frt/index.do.
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Enfermeiras e Enfermeiros , Saúde da Mulher , Humanos , Feminino , República da Coreia/epidemiologia , Adulto , Estudos Prospectivos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Enfermeiras e Enfermeiros/psicologia , COVID-19/epidemiologia , Gravidez , Estudos de Coortes , Inquéritos Epidemiológicos , Nível de Saúde , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, caused by a complex interplay of genetic and environmental factors. This study aimed to evaluate the combined efficacy of multi-polygenic risk scores and pooled cohort equations (PCE) for predicting future CVD risks in the Korean population. In this longitudinal study, 7,612 individuals from the Ansan and Ansung cohorts were analyzed over a 17-year follow-up period. The participants were genotyped using the Korea Biobank Array, and quality-controlled genetic data were subjected to imputation analysis. The weighted sum of the PRSs (wPRSsum) was calculated using PRS-CS with summary statistics from myocardial infarction, ischemic stroke, coronary artery disease, and hypertension genome-wide association studies. The recalibrated PCE was used to assess clinical risk, and the participants were stratified into risk groups based on the wPRSsum and PCE. Associations between these risk scores and incident CVD were evaluated using Cox proportional hazards models and Kaplan-Meier analysis. The wPRSsum approach showed a significant association with incident CVD (HR = 1.15, p = 7.49 × 10-5), and the top 20% high-risk genetic group had an HR of 1.50 (p = 5.04 × 10-4). The recalibrated PCE effectively differentiated between the low and high 10-year CVD risk groups, with a marked difference in survival rates. The predictive models constructed using the wPRSsum and PCE demonstrated a slight improvement in prediction accuracy, particularly among males aged <55 years (C-index = 0.640). We demonstrated that while the integration of wPRSsum with PCE did not significantly outperform the PCE-only model (C-index: 0.703 for combined and 0.704 for PCE-only), it provided enhanced stratification of CVD risk. The highest risk group, identified through the combination of high wPRSsum and PCE scores, exhibited an HR of 4.99 for incident CVD (p = 1.45 × 10-15). These findings highlight the potential of integrating genetic risk assessments with traditional clinical tools for effective CVD risk stratification. Although the addition of wPRSsum to the PCE provided a marginal predictive improvement, it proved valuable in identifying high-risk individuals and supporting personalized treatment strategies. This study reinforces the utility of multi-PRS in conjunction with clinical risk assessment tools, paving the way for more tailored approaches for CVD prevention and management in diverse populations.
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This study presents the nutrition survey methods and the updated food composition database for the Korean Genome and Epidemiology Study (KoGES). The KoGES, which is the largest and longest cohort study in Korea, aims to identify genetic and environmental factors associated with chronic diseases. This study has collected dietary data using a validated semi-quantitative food frequency questionnaire and/or the 24-hour recall method. However, these dietary survey methods use different food composition databases, and their nutritional values are out of date. Therefore, it became necessary to update the food composition database by revising nutrient analysis values to reflect improvements in the performance of food ingredient analysis equipment, revising international values to analysis values of Korean agricultural products, adjusting nutrient units, and adding newly reported nutrients related to chronic diseases. For this purpose, we integrated the different food composition databases used in each nutrition survey, updated 23 nutrients, and expanded 48 new nutrients for 3,648 food items using the latest reliable food composition databases published by national and international institutions. This revised food composition database may help to clarify the relationship between various nutrients and chronic diseases. It could serve as a valuable resource for nutritional, epidemiological, and genomic research and provide a basis for determining public health policies.
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Bases de Dados Factuais , Inquéritos Nutricionais , Humanos , República da Coreia/epidemiologia , Estudos de CoortesRESUMO
BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.
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Fogachos , Menopausa , Pessoa de Meia-Idade , Feminino , Humanos , Fogachos/epidemiologia , Depressão/epidemiologia , Estudos de Coortes , Estudos Transversais , SudoreseRESUMO
BACKGROUND: Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT). METHODS: We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose-response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels. RESULTS: Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3-4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12-23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3-4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3-4 days/week, regardless of whether the RT duration was 1-2 years or more than 2 years. CONCLUSIONS: Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3-4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years.
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BACKGRUOUND: To investigate the association between the time-varying resting heart rate (RHR) and change in RHR (∆RHR) over time and the risk of diabetes mellitus (DM) by sex. METHODS: We assessed 8,392 participants without DM or atrial fibrillation/flutter from the Korean Genome and Epidemiology Study, a community-based prospective cohort study that was initiated in 2001 to 2002. The participants were followed up until December 31, 2018. Updating RHR with biennial in-study re-examinations, the time-varying ∆RHR was calculated by assessing the ∆RHR at the next follow-up visit. RESULTS: Over a median follow-up of 12.3 years, 1,345 participants (16.2%) had DM. As compared with RHR of 60 to 69 bpm, for RHR of ≥80 bpm, the incidence of DM was significantly increased for both male and female. A drop of ≥5 bpm in ∆RHR when compared with the stable ∆RHR group (-5< ∆RHR <5 bpm) was associated significantly with lower risk of DM in both male and female. However, an increase of ≥5 bpm in ∆RHR was significantly associated with higher risk of DM only in female, not in male (hazard ratio for male, 1.057 [95% confidence interval, 0.869 to 1.285]; and for female, 1.218 [95% confidence interval, 1.008 to 1.471]). CONCLUSION: In this community-based longitudinal cohort study, a reduction in ∆RHR was associated with a decreased risk of DM, while an increase in ∆RHR was associated with an increased risk of DM only in female.
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Diabetes Mellitus , Frequência Cardíaca , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Frequência Cardíaca/fisiologia , Estudos Prospectivos , Fatores de Risco , República da Coreia/epidemiologia , Diabetes Mellitus/epidemiologia , Incidência , Adulto , Idoso , Fatores Sexuais , Seguimentos , Descanso/fisiologia , Fatores de TempoRESUMO
OBJECTIVES: We aimed to assess the serum folate, vitamin B12, and homocysteine status in Korean adolescents and adults using national data. METHODS: Blood samples were collected from participants aged ≥10 years in the Korea National Health and Nutrition Examination Survey 2013-2015. The stored serum samples were used to measure folate, vitamin B12, and homocysteine concentrations. A total of 8,016 participants were included in this analysis. Unweighted descriptive statistics and adjusted geometric means of the B vitamins and homocysteine concentrations were estimated. RESULTS: Females had higher serum folate and vitamin B12 concentrations and lower serum homocysteine concentrations than males. Folate deficiency (<6.8 nmol/L) and hyperhomocysteinemia (>15 µmol/L) were found in 8.6% and 11.8% of males, respectively. Approximately 3% of males had low or marginally low vitamin B12 status (≤221 pmol/L). Folate and vitamin B12 deficiencies and hyperhomocysteinemia were found in <2% of females. Suboptimal folate status was prevalent among adolescents and young adults, while suboptimal vitamin B12 status and hyperhomocysteinemia were relatively higher in older adults. Adjusted mean homocysteine concentrations were sharply decreased from the first to second decile of serum folate in males. CONCLUSIONS: In the Korean population, the proportion of males who achieved desirable folate and homocysteine concentrations were lower than those of females. Although most Koreans have adequate vitamin B12, a suboptimal folate status is common, particularly among adolescents and young adults. These findings could establish a foundation for public health initiatives aimed at improving folate levels in the Korean population.
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Ácido Fólico , Hiper-Homocisteinemia , Vitamina B 12 , Adolescente , Idoso , Feminino , Humanos , Masculino , Adulto Jovem , Ácido Fólico/sangue , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/epidemiologia , Inquéritos Nutricionais , República da Coreia/epidemiologia , Vitamina B 12/sangueRESUMO
Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.
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Big Data , Doenças Raras , Humanos , Projetos Piloto , Genômica , República da Coreia/epidemiologia , Testes GenéticosRESUMO
BACKGROUND: Adverse lipid profiles are observed in postmenopausal women. However, there is insufficient evidence of the association between lipids and reproductive aging in Korean women. We aimed to characterize lipid changes with respect to timing relative to menopause in Korean middle-aged women. METHODS: This study included 1,436 premenopausal women who had a natural menopause during the follow-up period (median = 15.76 years) from the Korean Genome and Epidemiology Study (KoGES) Ansan and Anseong cohort. Lipid levels were measured every 2 years, and the magnitudes of annual lipid changes and differences in the changes by premenopausal body mass index were estimated using piecewise linear mixed-effects models. RESULTS: All lipid levels increased greatly from 3 or 5 years before menopause to 1 year after menopause in all women, regardless of their premenopausal body mass index. During the period, high-density lipoprotein cholesterol (HDL-C) levels increased at 0.42 mg/dL per year (95% confidence interval [CI], 0.29 to 0.55 mg/dL). Nevertheless, non-HDL-C levels simultaneously increased at 3.42 mg/dL per year (95% CI, 3.11 to 3.72 mg/dL), and an annual change in the non-HDL-C to HDL-C ratio was 0.05 (95% CI, 0.04 to 0.06). One year after menopause, changes in all lipid parameters significantly slowed down, except for the non-HDL-C to HDL-C ratio (P < 0.001 for all). The ratio continued to increase until 3 years after menopause, but thereafter, the change leveled off. CONCLUSION: Women experienced remarkable increases in lipid levels during menopausal transition, highlighting the need for early intervention strategies for cardiovascular disease prevention in women.
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Menopausa , Pré-Menopausa , Pessoa de Meia-Idade , Feminino , Humanos , Envelhecimento , Colesterol , HDL-Colesterol , República da Coreia , Triglicerídeos , Fatores de RiscoRESUMO
Objective: Depression is a serious mental disorder which is the leading cause of suicide. This study investigated the association between incident depression and 4-year leisure-time physical activity (PA) levels and/or resistance training (RT). Methods: This community-based Korean cohort included 3,967 participants without depression at baseline. The average PA-time (the total duration of moderate-intensity leisure-time PA) up to 4 years prior to baseline enrollment was calculated to evaluate the cumulative levels of PA. Participants were divided into four groups based on their average PA-time: "Non-PA," " <150 min/week," "150-299 min/week," and "≥300 min/week." Furthermore, based on compliance to PA guidelines (≥150 min/week of PA-time) and participation in RT, the participants were categorized into four subgroups: "Low-PA," "Low-PA+RT," "High-PA," and "High-PA+RT." A multivariate Cox proportional hazards regression model was used to assess the 4-year incidence of depression according to leisure-time PA levels and/or regularity of RT. Results: During the mean 3.72 ± 0.69 years of follow-up, 432 participants (10.89%) developed depression. In women, performing 150-299 min/week of moderate-intensity leisure-time PA was associated with a 38% risk reduction for incident depression (HR, 0.62; CI, 0.43-0.89; p < 0.05), whereas more than 300 min/week of that was related to a 44% risk reduction for incident depression (HR, 0.56; CI, 0.35-0.89; p < 0.05) as compared to that in the Non-PA group. However, in men, there was no significant relationship between the amount of leisure-time PA per week and the risk of incident depression. Moreover, in both sexes, RT had no significant effect on depression in either the Low-PA or High-PA group. Conclusions: There was an inverse dose-response association between leisure-time PA levels and incident depression only in women, whereas adding RT to high levels of PA had no significant effect on depression in either sex.
Assuntos
Depressão , Exercício Físico , Masculino , Humanos , Feminino , Depressão/epidemiologia , Atividade Motora , Atividades de Lazer , República da Coreia/epidemiologiaRESUMO
In botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women. Previous work has demonstrated that RCE reduces estrogen detoxification pathways in breast cancer cells (MCF-7) and, thus, may serve to negatively affect estrogen metabolism-induced chemical carcinogenesis. Clinical RCE contains ca. 30% of biochanin A and formononetin, which potentially mask activities of less abundant compounds. These two isoflavonoids are aryl hydrocarbon receptor (AhR) agonists that activate P450 1A1, responsible for estrogen detoxification, and P450 1B1, producing genotoxic estrogen metabolites in female breast cells. Clinical RCE also contains the potent phytoestrogen, genistein, that downregulates P450 1A1, thereby reducing estrogen detoxification. To identify less abundant bioactive constituents, countercurrent separation (CCS) of a clinical RCE yielded selective lipophilic to hydrophilic metabolites in six enriched DESIGNER fractions (DFs 01-06). Unlike solid-phase chromatography, CCS prevented any potential loss of minor constituents or residual complexity (RC) and enabled the polarity-based enrichment of certain constituents. Systematic analysis of estrogen detoxification pathways (ERα-degradation, AhR activation, CYP1A1/CYP1B1 induction and activity) of the DFs uncovered masked bioactivity of minor/less abundant constituents including irilone. These data will allow the optimization of RCE with respect to estrogen detoxification properties. The DFs revealed distinct biological activities between less abundant bioactives. The present results can inspire future carefully designed extracts with phytochemical profiles that are optimized to increase in estrogen detoxification pathways and, thereby, promote resilience in women with high-risk for breast cancer. The DESIGNER approach helps to establish links between complex chemical makeup, botanical safety and possible efficacy parameters, yields candidate DFs for (pre)clinical studies, and reveals the contribution of minor phytoconstituents to the overall safety and bioactivity of botanicals, such as resilience promoting activities relevant to women's health.