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The predominance of vaginal Lactobacillus species, specifically L. crispatus, is important for pregnancy maintenance, but varies by race. The composition of the vaginal microbiome can affect susceptibility to adverse pregnancy outcomes. We performed 16S rRNA gene amplicon sequencing on vaginal swabs taken from Korean pregnant women. Here, we report the transition of Lactobacillus spp. in samples of full-term birth (FTB) collected longitudinally in the second and third trimesters of pregnancy in a cohort study (n = 23) and their association with Lactobacillus abundance and preterm birth (PTB) in a case–control study (n = 200). Lactobacillus species, which was dominant in FTB samples including those that received interventions in the second trimester, did not change until 37 weeks of gestation. However, L. crispatus was replaced by other Lactobacillus species after 37 weeks. The PTB risk showed a closer association with the Lactobacillus abundance than with community state type determined by Lactobacillus species. PTB was associated with less than 90% of Lactobacillus abundance and an increase in Ureplasma parvum in the second trimester. Thus, the vaginal microbiome may change in preparation for childbirth in response to multiple intrinsic factors after 37 weeks of gestation. Monitoring the Lactobacillus abundance may help improve the reliability of microbial PTB biomarkers.

Ureaplasma and Prevotella infections are well-known bacteria associated with preterm birth. However, with the development of metagenome sequencing techniques, it has been found that not all Ureaplasma and Prevotella colonizations cause preterm birth. The purpose of this study was to determine the association between Ureaplasma and Prevotella colonization with the induction of preterm birth even in the presence of Lactobacillus. In this matched case-control study, a total of 203 pregnant Korean women were selected and their cervicovaginal fluid samples were collected during mid-pregnancy. The microbiome profiles of the cervicovaginal fluid were analyzed using 16S rRNA gene amplification. Sequencing data were processed using QIIME1.9.1. Statistical analyses were performed using R software, and microbiome analysis was performed using the MicrobiomeAnalyst and Calypso software. A positive correlation between Ureaplasma and other genera was highly related to preterm birth, but interestingly, there was a negative correlation with Lactobacillus and term birth, with the same pattern observed with Prevotella. Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth, although Ureaplasma and Prevotella are associated with preterm birth. Balanced colonization between Lactobacillus and Ureaplasma and Prevotella is important to prevent preterm birth.

This nationwide population-based cohort study aimed to investigate the impact of systemic anti-inflammatory treatment on the major adverse cardiovascular events (MACE) risk in patients with psoriasis from January 2006 to December 2018, using a database provided by the Korean National Health Insurance Service. Patients were grouped based on the following treatment modalities: biologics, phototherapy, methotrexate, cyclosporine, and mixed conventional systemic agents. Patients who had not received any systemic treatment were assigned to the control cohort. The incidence of MACE per 1000 person-year was 3.5, 9.3, 12.1, 28.4, 39.5, and 14.5 in the biologic, phototherapy, methotrexate, cyclosporine, mixed conventional systemic agents, and control cohorts, respectively. During the 36-month follow-up, the cumulative incidence of MACE in the phototherapy and biologic cohorts remained lower than that of other treatment modalities. Cyclosporine (hazard ratio (HR) = 2.11, 95% confidence interval (CI) = 1.64–2.71) and mixed conventional systemic agents (HR = 2.57, 95% CI = 2.05–3.22) treatments were associated with increased MACE risk. Methotrexate treatment was not associated with MACE. Our finding demonstrates that treatment modalities may affect cardiovascular comorbidities in patients with psoriasis. Thus, an appropriate combination of anti-psoriatic therapies should be considered to manage patients with high cardiovascular risk.IRB approval status: Waiver decision was obtained by the institutional review board, Konkuk University Hospital, Seoul, Republic of Korea (KUH1120107).

Phthalates are well-known endocrine-disrupting chemicals. Many detrimental health effects of phthalates were investigated, but studies on the association of phthalates with obesity in children showed inconsistent results. Thus, this systematic review and meta-analysis were performed to clarify whether prenatal and postnatal exposures to phthalates are associated with physical growth disturbances in children. We performed the systematic review and meta-analysis following the PRISMA 2020 statement guidelines, and found 39 studies that met our inclusion criteria, including 22 longitudinal and 17 cross-sectional studies. We observed a significant negative association between the prenatal exposure to DEHP and the body mass index (BMI) z-score of the offspring (β = − 0.05; 95% CI: − 0.10, − 0.001) in the meta-analysis, while no significant association between the prenatal exposure to DEHP and the body fat percentage of the offspring was observed (β = 0.01; 95% CI: − 0.41, 0.44). In the systematic review, studies on the association between phthalates exposure in childhood and obesity were inconsistent. Prenatal exposure to phthalates was found to be associated with decreased BMI z-score in children, but not associated with body fat percentage. Our findings suggest that phthalates disturb the normal muscle growth of children, rather than induce obesity, as previous studies have hypothesized.

We aimed to examine the association between physical activity (PA) level and dynapenia in older adults with chronic obstructive pulmonary disease (COPD), and whether it varied with sex and obesity status. The current cross-sectional study included total of 1033 community-dwelling participants with COPD aged 65–79 from the Korean National Health and Nutrition Examination Survey. In the multivariable model, high and moderate PA levels were significantly associated with lower odds of dynapenia than low PA levels (high PA level: odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.09–0.74; moderate PA level: OR = 0.55, 95% CI = 0.35–0.87). This inverse association was observed only in males with COPD (high PA level: OR = 0.17, CI = 0.04–0.65; moderate PA level: OR = 0.49, 95% CI = 0.27–0.88) and the normal-weight group (18.5 ≤ body mass index (BMI) 2; high PA level: OR = 0.21, 95% CI = 0.05–0.88; moderate PA level: OR = 0.48, 95% CI = 0.27–0.86). In older community-dwelling patients with COPD, a negative dose-dependent relationship exists between PA level and dynapenia. The independent associations between PA level and dynapenia was significant in men and in participants with normal weight.

Insects have acquired various types of wings over their course of evolution and have become the most successful terrestrial animals. Consequently, the essence of their excellent environmental adaptability and locomotive ability should be clarified; a simple and versatile method to artificially reproduce the complex structure and various functions of these innumerable types of wings is necessary. This study presents a simple integral forming method for an insect-wing-type composite structure by 3D printing wing frames directly onto thin films. The artificial venation generation algorithm based on the centroidal Voronoi diagram, which can be observed in the wings of dragonflies, was used to design the complex mechanical properties of artificial wings. Furthermore, we implemented two representative functions found in actual insect wings: folding and coupling. The proposed crease pattern design software developed based on a beetle hindwing enables the 3D printing of foldable wings of any shape. In coupling-type wings, the forewing and hindwing are connected to form a single large wing during flight; these wings can be stored compactly by disconnecting and stacking them like cicada wings.

We evaluated trajectories of glycated hemoglobin (HbA1c) levels and body mass index z-scores (BMIz) for 5 years after diagnosis among Korean children and adolescents with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the common data model. From the de-identified database of three hospitals, 889 patients p p p

Accurate risk stratification according to the extent of Langerhans cell histiocytosis (LCH) determined on whole-body evaluation is important for determining the treatment plans and prognosis in patients with LCH. This study aimed to compare the lesion detectability and the accuracy of risk stratification of skeletal survey, bone scan, and whole-body magnetic resonance imaging (WB-MRI) in patients with LCH. Patients with newly-diagnosed LCH who underwent all three imaging modalities were retrospectively included (n = 46). The sensitivity and mean number of false-positives per patient for LCH lesions, and the accuracy of risk stratification of each modality were assessed. WB-MRI had significantly higher sensitivity (99.0%; 95% confidence interval, 93.2–99.9%) than skeletal survey (56.6%; p 0.017). WB-MRI tended to have higher accuracy for the risk stratification than skeletal survey and bone scan (concordance rate of 0.98, 0.91, and 0.83, respectively), although the differences were not significant (overall p-value 0.066). In conclusion, WB-MRI had higher detectability for LCH lesions than skeletal survey and bone scan, while the three whole-body imaging modalities had comparable accuracy in the initial risk stratification of LCH.

Prematurity, size at birth, and postnatal growth are important factors that determine cardiometabolic and neurodevelopmental outcomes later in life. In the present study, we aimed to investigate the associations between the size at birth and growth velocity after birth with cardiometabolic and neurodevelopmental outcomes in preterm infants. Fifty-six preterm infants born at p = 0.036) and perceptional reasoning index (β = 0.456, p = 0.003) of K-WISC-IV were positively correlated with postnatal weight gain in the neonatal intensive care unit. Although cardiometabolic outcomes were comparable in preterm SGA and AGA infants, the growth velocity at different time periods resulted in different cardiometabolic and neurocognitive outcomes. Thus, ensuring an optimal growth velocity at early neonatal period could promote good neurocognitive outcomes, while adequate growth after 1 year could prevent adverse cardiometabolic outcomes in preterm infants.

Preterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. However, due to the redundant nature of the clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of PTB. To identify molecular signatures predictive of PTB with high accuracy, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) as well as cellular pathways represented by the DEGs between PTB and FTB. By integrating the gene expression profiles of different ethnic groups from previous studies, we identified the core T-cell activation pathway associated with PTB, which was shared among all previous datasets, and selected three representative DEGs (CYLD, TFRC, and RIPK2) from the core pathway as mRNA signatures predictive of PTB. We confirmed the dysregulation of the candidate predictors and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 are potentially reliable predictors for PTB.

Electrospinning is a simple versatile process used to produce nanofibers and collect them as a nanofiber mat. However, due to bending instability, electrospinning often produces a nanofiber mat with non-uniform mat thickness. In this study, we developed a uniform-thickness electrospun nanofiber mat (UTEN) production system with a movable collector based on real-time thickness measurement and thickness feedback control. This system is compatible with a collector with void regions such as a mesh-type collector, two-parallel-metal-plate collector, and ring-type collector, which facilitates the measurement of light transmittance across the produced nanofiber mat during electrospinning. A real-time measurement system was developed to measure light transmittance and convert it to the thickness of the nanofiber mat in real time using the Beer–Lambert law. Thickness feedback control was achieved by repeating the following sequences: (1) finding an optimal position of the movable collector based on the measured thickness of the nanofiber mat, (2) shifting the collector to an optimal position, and (3) performing electrospinning for a given time step. We found that the suggested thickness feedback control algorithm could significantly decrease the non-uniformity of the nanofiber mat by reducing the standard deviation by more than 8 and 3 times for the numerical simulation and experiments, respectively, when compared with the conventional electrospinning. As a pioneering research, this study will contribute to the development of an electrospinning system to produce robust and reliable nanofiber mats in many research and industrial fields such as biomedicine, environment, and energy.

Cytochrome P450 (CYP) is involved in the metabolism of nevirapine (NVP); especially, CYP2B6 has been known to be one of the main enzymes involved in NVP metabolism. The objective of this study was to investigate the effects of CYP2B6 variants on plasma concentrations of NVP by a systematic review and meta-analysis. A search for qualifying studies published until April 2020 was conducted using the EMBASE, PubMed, and Web of Science databases. The mean difference (MD) and 95% confidence intervals (CIs) were calculated. Data analysis was performed using R Studio (version 3.6) and Review Manager (version 5.3). In total, data from six studies involving 634 patients were analyzed in the systematic review and five studies in the meta-analysis. We found that carriers of the CYP2B6 516TT genotype had a 2.18 µg/mL higher NVP concentration than did the GG or GT (95% CI 1.28–3.08). In the respective comparisons of the three genotypes, it was found that the MD was 1.87 µg/mL between the TT and GT groups, 2.53 µg/mL between TT and GG, and 0.60 µg/mL between GT and GG. This meta-analysis confirmed that CYP2B6 polymorphisms was associated with plasma NVP concentrations. Therefore, CYP2B6 genotyping may be useful to predict the responses to NVP.

The roles of individual bacteria and their relationship in the development of colorectal cancer (CRC) remain unclear. We aimed to determine the prevalence of CRC-associated bacteria using quantitative real-time PCR (qPCR) or 16S rRNA analysis and the statistical correlations of patient demographics and clinical characteristics comprising alcohol consumption with CRC-associated bacteria. We determined the prevalence of five CRC-associated bacterial species in 38 CRC patients (39 samples) and 21 normal individuals using qPCR, and the relative abundance of bacterial taxa in the gut microbiome was assessed using 16S rRNA analysis. Fusobacterium nucleatum was the only bacterium that was significantly (P Fusobacterium, Peptostreptococcus, Collinsella, Prevotella, Parvimonas, and Gemella, in patients with CRC. An integrated analysis using 16S rRNA data and epidemiological characteristics showed that alcohol consumption was significantly correlated with the abundance of Fusobacterium OTUs. The correlation of alcohol consumption with the abundance of Fusobacterium OTUs in cancer tissue discovered using 16S rRNA analysis suggests a possible link between alcohol metabolism and subsequent tumorigenesis caused by F. nucleatum.

SLC39A8 encodes ZIP8, a divalent metal ion transporter. Mutations in the SLC39A8 gene are associated with congenital disorder of glycosylation type II and Leigh syndrome. Notably, affected patients with both disorders exhibited severe manganese (Mn) deficiency. The cellular function of human SLC39A8 (hSLC39A8) and the mechanisms by which mutations in this protein lead to human diseases are unclear. Herein, we show that hSLC39A8 mediates 54Mn uptake by the cells, and its expression is regulated by Mn. While expression of wild-type hSLC39A8 increased 54Mn uptake activity, disease-associated mutations abrogated the ability of the transporter to mediate Mn uptake into the cells, thereby providing a causal link to severe Mn deficiency. All mutants failed to localize on the cell surface and were retained within the endoplasmic reticulum. Interestingly, expression of hSLC39A8 mutants of both CDG type II and Leigh syndrome reduced mitochondrial 54Mn levels and activity of Mn-dependent mitochondrial superoxide dismutase MnSOD, and in turn increased oxidative stress. The expression of wild-type hSLC39A8, but not the disease-associated mutants, promoted mitochondrial functions. Moreover, loss of function analyses further corroborate hSLC39A8’s critical role in mediating Mn uptake and mitochondrial function. Our results provide a potential pathogenic mechanism of diseases that are associated with hSLC39A8 mutations.

National antimicrobial usage and prescription patterns during the 12 years from 2002 to 2013 were analyzed using the National Health Insurance Service-National Sample Cohort. Antimicrobial usage was analyzed by major illness, sex, age, area of residence, income rank, diagnosis, and type of medical institution for each year. Total antimicrobial prescriptions increased from 15.943 daily defined dose (DDD)/1,000 inhabitants/day in 2002 to 24.219 in 2013. In 2013, 72% of total prescriptions were administered in clinics. Antimicrobials were most frequently prescribed to children younger than 10 years, followed by adults aged 70 years or older and those aged 60–69 years. Penicillins and cephems were the most popular classes of antimicrobial used. In 2013, 48% of total antibiotic usage (11.683 DDD/1,000 inhabitants/day) was due to respiratory diseases. After the Korean government has implemented a series of healthcare policies, antibiotic prescription decreased for the treatment of upper respiratory infection, the causative agents are mostly viruses.

Because healthcare workers (HCWs) are at high risk for tuberculosis (TB) infection, it is essential to research the prevalence of latent TB infection (LTBI) and to implement health interventions including early treatment of LTBI and TB infection control measures. The purpose of the study was to determine the prevalence and risk factors for LTBI using interferon-γ release assay (IGRA) among HCWs in South Korea. The cross-sectional study was carried in the National Health Insurance Service Ilsan Hospital, which is a 740-bed general hospital, South Korea. HCWs who participated in this survey were required to complete a questionnaire and IGRA was performed. Of the 1,655 HCWs, 271 results were positive and the prevalence of LTBI was 16% (95% CI; 15–18%). In the multivariate analysis, age (OR; 2.201, 95% CI; 1.911–2.536, P

Due to the spread of a single CTX-M-type extended-spectrum β-lactamase (ESBL) clone of sequence type (ST) 131, community-onset bacteremia caused by ESBL-producing Escherichia coli has increased dramatically. We evaluated the risk factors and molecular features of ESBL-producing E. coli ST131 clones isolated from Korean patients with community-onset bacteremia. We collected a total of 124 ESBL-producing E. coli isolates from blood in patients with community-onset bacteremia over a 2 year-period. Among 124 patients, the number of community-associated bacteremia cases was 57 (46%). ST131 strains accounted for 49.1% (28/57) of community-associated bacteremia cases and 44.8% (30/67) of healthcare-associated community-onset bacteremia cases. Among 58 ST131 strains, nine isolates were shown to harbor O16-H41, and 61.1% (30/49) of O25 had H30Rx. In a multivariate analysis, independent risk factors for acquisition of ST131 isolates over non-ST131 isolates were underlying diabetes mellitus and absence of prior chemotherapy history. The most common ESBL genotype was CTX-M-15 (46.0%), followed by CTX-M-14 (37.1%). A considerable proportion of community-onset ESBL-producing E. coli bacteremia was observed. ST131 clones appear to be associated with the spread of community-associated bacteremia exhibiting high antimicrobial resistance and highly virulent H30Rx traits, which could become a major public health concern in Korea.

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10–19 years old) and young adults (20–29 years old). Data from the Korea Health and Nutrition Examination Survey (2011–2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10–29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P P

Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid and cholesterol homeostasis via fatty acid oxidation and lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds SREBP to prevent SREBP translocation to the Golgi apparatus during nutrient starvation in the liver. However, the regulation of SREBP-1c processing by INSIGs during fasting and the regulatory mechanisms of the mouse Insig2a gene expression have not been clearly addressed. In the present study, we found that Insig2a was upregulated by PPARα in mouse livers and primary hepatocytes during fasting, whereas Insig2a mRNA expression was decreased in the livers of refed mice. A PPAR-responsive element between −126 bp and −114 bp in the Insig2a promoter was identified by a transient transfection assay and a chromatin immunoprecipitation assay; its role in regulation by PPARα was characterised using Pparα-null mice. These results suggest that PPARα is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.

Aberrant Wnt/β-catenin signalling is implicated in the progression of several human cancers, including non-small cell lung cancer (NSCLC). However, mutations in Wnt/β-catenin pathway components are uncommon in NSCLC, and their epigenetic control remains unclear. Here, we show that KIF3A, a member of the kinesin-2 family, plays a role in suppressing Wnt/β-catenin signalling in NSCLC cells. KIF3A knockdown increases both β-catenin levels and transcriptional activity with concomitant promotion of malignant potential, such as increased proliferation and migration and upregulation of stemness markers. Because KIF3A binds β-arrestin, KIF3A depletion allows β-arrestin to form a complex with DVL2 and axin, stabilizing β-catenin. Although primary cilia, whose biogenesis requires KIF3A, are thought to restrain the Wnt response, pharmacological inhibition of ciliogenesis failed to increase β-catenin activity in NSCLC cells. A correlation between KIF3A loss and a poorer NSCLC prognosis as well as β-catenin and cyclin D1 upregulation further suggests that KIF3A suppresses Wnt/β-catenin signalling and tumourigenesis in NSCLC.