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Whether beverage consumption is associated with longitudinal observation of telomere length remains unclear. We evaluated the association of green tea, coffee, and soft drink consumption with 6-year changes in leukocyte telomere length (LTL). The study included 1952 participants who provided whole blood samples for LTL assays during the baseline (year 2011–2012) and follow-up (year 2017–2018) periods and reported baseline information on consumption of green tea, coffee, and soft drinks. Robust regression analysis was used to analyze the association adjusted for potential confounding variables. In the results, an inverse association between green tea consumption and LTL changes from baseline, which indicate telomere shortening, was found; regression coefficient [95% confidence interval] was − 0.097 [− 0.164, − 0.029] for participants who daily consumed at least 1 cup of green tea compared with non-consumers ( p value = 0.006). This association was stronger among women (versus men) and younger participants aged 50–64 years (versus older). However, a positive association between soft drink consumption and LTL shortening was observed among women ( p value < 0.05). Coffee consumption was not associated with LTL changes. These findings suggested that green tea consumption may be protective against telomere shortening reflecting biological aging whereas coffee and soft drink consumption may not.

Tumour size and extrathyroidal extension (ETE) may impact papillary thyroid carcinoma (PTC) outcomes. We therefore examined the prognostic value of tumour size and ETE for predicting posttreatment recurrence in PTC patients. A total of 2,902 patients who underwent thyroidectomy for previously untreated T1–T3 PTC (7th edition American Joint Committee on Cancer) at our tertiary referral center were included. Univariate and multivariate Cox proportional hazard regression analyses were used to determine significant factors predictive of posttreatment recurrence-free survival (RFS). In univariate analysis, tumour factors (including tumour size, multifocality, ETE, and lymphovascular invasion), nodal factors (including positive lymph node number, lymph node ratio, and extranodal extension), and MACIS (metastases, age, completeness of resection, invasion, and size) scores were significantly associated with RFS outcomes (P < 0.001). In multivariate analysis, tumour size >4 cm (P < 0.001) and multifocality (P = 0.038) were the independent factors of RFS. Nodal factors and MACIS scores were also independent factors of RFS. Tumour size impacts RFS after thyroidectomy in T1–T3 PTC patients. •Minimal and macroscopic extrathyroidal extension (ETE) were found in 1,382 (47.6%) and 329 (11.3%) of 2,902 patients, respectively.•ETE was significantly associated with adverse pathological tumor findings and nodal findings.•In univariate analyses, tumor size and ETE were significantly associated with recurrence-free survival (RFS).•In multivariate analysis, tumor size >4 cm, but not ETE, was the independent factor of RFS.•Minimal or macroscopic ETE showed only a modest decrease in RFS compared with tumor size. This study examined the prognostic value of tumor size and extrathyroidal extension on recurrence in 2,902 patients with pathological T1–T3 PTC. In multivariate analysis, tumor size >4 cm, but not microscopic or macroscopic extrathyroidal extension, was the independent factor of recurrence-free survival.

Objective To evaluate the individual and combined effects of obesity and muscle mass on brain volume in a community-dwelling healthy older population. Methods One thousand two hundred nine participants (M:F = 574:635, mean age 63.6 ± 6.9 years) were included. The cross-sectional area of visceral fat (VF), the height-adjusted appendicular skeletal muscle mass (ASM/height 2 ), and the ratio of thigh muscle to visceral fat (TM/VF) represented obesity, muscle mass, and their integrated value, respectively. Linear regression analysis was performed to establish associations between 215 brain compartment volumes and VF, ASM/height 2 , and TM/VF after adjusting for covariates. Results On regression analysis, TM/VF had a positive correlation to the volumes of temporal lobe and cerebellum. TM/VF was associated with volumes of 10 subcompartments. TM/VF was positively correlated with the volumes of left entorhinal cortex, right temporal pole and inferior temporal gyrus related to cognition ( p  < 0.05, respectively), and the volumes of cerebellum and right pallidum related to movement ( p  < 0.05, respectively). However, VF had a negative correlation to temporal lobe volume and ASM/height 2 had no significant correlation to any of the brain lobes. VF and ASM/height 2 were correlated with volumes of 5 subcompartments and one subcompartment, respectively, Conclusions TM/VF reflects the integrated effect of obesity and muscle mass and is associated with the volume of more brain regions compared to indices of obesity or muscle mass alone. The positive effect of muscle mass and the negative effect of obesity change the volumes of brain regions related to cognition and movement which were not significantly affected by obesity or muscle mass alone. Key Points • If obesity and muscle mass were considered together, we could find more significant brain volume changes which were not found in obesity or muscle alone. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of entorhinal cortex, temporal pole, and inferior temporal gyrus related to cognition. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of cerebellum and pallidum related to movement.

To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury. Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties. Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties. Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic ( N  = 393), clinical ( N  = 5032), genomic ( N  = 8842), and metabolite ( N  = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g , an unclassified Lachnospiraceae , was associated with T2D ( β  = −189.13; p  = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate ( r  = −0.0938 and −0.0829, respectively; p  = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels ( β  = 0.0002; p  = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels. Diabetes: a little help from the microbiome A microbe that may help protect against type II diabetes has been detected by examining extracellular vesicles (EVs), tiny membrane-wrapped packages secreted by human cells and by the bacteria making up the microbiome. Examining EVs allows researchers to sample microbial populations other than the intensively studied intestinal microbiome. Sungho Won, Seoul National University, and Geum-Sook Hwang, Korea Basic Science Institute, Seoul, and coworkers studied the microbial EVs in urine samples collected from South Korean subjects over four years. They identified a previously unclassified bacterial species in the family Lachnospiraceae that was associated with lower risk of developing type II diabetes. Further investigation showed that these bacteria may break down ketone bodies, metabolic byproducts that signal disrupted sugar metabolism leading to diabetes. These results contribute to understanding how the microbiome contributes to metabolic health and disease.

Hyung-Lae Kim and colleagues report a genome-wide association study of quantitative traits of biomedical importance in Koreans. Although some loci were previously detected in European populations, others are new. To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 × 10 −9 ) and 6q22 (rs12110693, P = 1.6 × 10 −9 ), with the latter ∼400 kb from the coding sequence of GJA1 . For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 × 10 −7 ). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 × 10 −12 ) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius ( P = 1.0 × 10 −11 ), tibia ( P = 1.6 × 10 −6 ) and heel ( P = 1.9 × 10 −10 ). On chromosome 7p14, rs1721400 (mapping close to SFRP4 , a frizzled protein gene) showed consistent associations at the same three sites ( P = 2.2 × 10 −3 , P = 1.4 × 10 −7 and P = 6.0 × 10 −4 , respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.

Muscle strength is associated with type 2 diabetes mellitus (T2DM). However, it is controversial whether muscle strength and normalized muscle strength is a risk factor for T2DM. Moreover, the relationship of back muscle strength (BMS) and incident T2DM has not been reported. In this study, we investigated the relationship between HGS, BMS, normalized HGS and BMS, and incident T2DM. A total of 2699 non-diabetes subjects aged 40-69 years (1313 women and 1386 men) in the Korean Genome and Epidemiology Study (KoGES) Ansan cohort were followed for 16 years. At the baseline and biennial follow-up visits, fasting glucose, postprandial 2-h glucose, clinical examinations, HGS, and BMS were measured by trained interviewers and examiners. HGS and BMS were measured at baseline. The relationships between incident T2DM, HGS, BMS, and normalized HGS and BMS were estimated using Cox proportional hazard regression models after adjusting for the confounding factors. HGS and BMS were not associated with incident T2DM in multivariate analysis. However, the hazard ratio (HR) per one standard deviation (SD) increase in the body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR)-normalized HGS, and BMS was associated with a lower risk for incident T2DM in both women and men after adjusting for the confounding factors (HR = 0.842-0.880-fold for women, p ≤ 0.015; HR = 0.887-0.903-fold for men, p ≤ 0.024). In the sub-analysis of menopause status, the HR per one SD increase in BMI, weight , WC, and WHR-normalized HGS was associated with a lower risk for incident T2DM in both pre- and post-menopausal women after adjusting for the confounding factors (HR = 0.860-0.820-fold for premenopausal, P ≤ 0.006; HR = 0.900-0.867-fold for postmenopausal, p ≤ 0.024). Additionally, we confirmed that the quartile group with higher muscle strength was associated with a lower risk for incident T2DM. The present study suggested that normalized HGS and BMS were associated with a lower risk for the future development of T2DM. Moreover, weak muscle strength in premenopausal women may be the cause of T2DM. Further research is needed to determine whether efforts to improve muscle strength, such as exercise can reduce the risk of T2DM.

Abstract Study Objectives To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition. Methods We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links. Results Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea–hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40). Conclusions Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships. Graphical Abstract Graphical Abstract

Objective The Epworth sleepiness scale (ESS) is widely used to measure the subject's average sleep propensity across those different situations in daily life, particularly in patients with sleep-disordered breathing. The purposes of this study were to test the hypothesis that the Korean version of the ESS (KESS) is valid and evaluate its usefulness. Materials and methods We developed the KESS, which involved translating into Korean and then translating back into English to check its accuracy. A total of 273 participants (181 obstructive sleep apnea (OSA)—37 mild, 61 moderate, 83 severe, 32 simple snoring and 60 normal) were included in this study. All subjects completed the overnight polysomnograph and 53 of the total subjects were randomly selected for a retest with the questionnaire approximately 2∼4 weeks later. The associations between KESS and the degree of OSA were examined through ANCOVA, adjusted for age, sex and BMI . Results The total score and each item's score of KESS in patients with OSA were significantly higher than subjects with normal controls ( p  < 0.01). As the severity of OSA increased, the KESS showed significantly increasing patterns ( p for trend <0.01). The KESS in patient groups showed good internal consistency (Cronbach's α  = 0.90) and test–retest reliability ( r  = 0.78 to 0.93). Conclusion The KESS is a reliable and valid tool for screening patients with daytime sleepiness in Korea.

Objectives Repetitive unbalances and tensions generated by inspiratory efforts against an obstructive upper airway during sleep predispose the development of expiratory central airway collapse. In addition, structures of the upper airway between men and women have differences and could be the reasons for differences in obstructive sleep apnea (OSA) prevalence between genders. The present study aimed to evaluate the association between parameters of expiratory dynamic tracheal collapse measured using chest multidetector CT and objectively measured OSA severity between men and women. Materials and methods A total of 901 participants who underwent chest CT and overnight in-home polysomnography from the Korean Genome and Epidemiology Study were cross-sectionally analyzed (women: 46.2%). The participants were divided into three groups based on OSA severity by apnea–hypopnea index (AHI). Multivariate linear regression analysis was performed to determine the effects of central airway collapse after adjustment for cardiovascular-related covariates. Results In a multivariate analysis, percentages of expiratory lumen structure reductions involving area, diameter, and perimeter were associated with AHI (all p values < 0.05) and with OSA severity (moderate-to-severe OSA than no OSA: β  = 3.30%, p  = 0.03; β  = 2.05%, p  = 0.02; β  = 1.97%, p  = 0.02, respectively) in women, whereas men had only a greater percentage of expiratory wall thickness reduction in moderate-to-severe OSA than no OSA ( β  = 0.72%, p  = 0.003). In addition, women with both mild OSA and moderate-to-severe OSA had higher expiratory tracheal collapse than men without OSA, and a moderate effect of sex was observed ( p for interaction = 0.007). Conclusion The expiratory dynamic tracheal collapse was independently associated with severity of OSA in women than in men. Clinical relevance statement Differences of pharyngeal structures and inherent features of airways by genders may affect the dissimilarities in vulnerability to sleep apnea between men and women. Key Points • The expiratory dynamic tracheal collapse was independently associated with severity of OSA in women than in men. • Women with over mild OSA had higher expiratory tracheal collapse than men without OSA, and moderate effect of sex was observed. • Structural differences of airway may affect differences in susceptibility of sleep apnea between genders.