Korea National Institute of Health

Evidence on whether the association between vitamin D levels and diabetes risk differs across glycemic statuses is limited. We investigated the association between circulating vitamin D levels and type 2 diabetes risk according to glycemic status. This prospective cohort study included 3604 participants without diabetes (mean age: 56 years) whose serum 25-hydroxyvitamin D (25(OH)D) levels were measured in the community-based Korean Genome Epidemiology Study (2007-2009). Fasting and 2-h post-load glucose and glycated hemoglobin (HbA1c) levels were measured biannually over a 14-year follow-up period. Season-standardized serum 25(OH)D levels were categorized into <25 (deficient), 25-50 (insufficient), and ≥ 50 nmol/L (sufficient). We assessed the association between serum 25(OH)D levels and type 2 diabetes risk using Cox proportional hazards models with time-varying covariates, stratifying by glycemic status and individual glycemic markers. Over 43,176 person-years of follow-up, 796 participants developed type 2 diabetes. Compared with participants with vitamin D deficiency, the multivariable-adjusted hazard ratios (95% confidence intervals) for type 2 diabetes in those with vitamin D sufficiency were 0.80 (0.62-1.04) overall, 0.55 (0.32-0.97) in participants with normoglycemia, and 0.93 (0.69-1.24) in those with prediabetes (P for interaction by glycemic status = 0.04). The association between serum 25(OH)D levels and diabetes risk differed according to HbA1c level (P for interaction = 0.05); a trend toward a lower risk of type 2 diabetes was observed in participants with HbA1c < 5.7% but not in those with HbA1c 5.7-6.4%. The association between serum 25(OH)D levels and the risk of type 2 diabetes differed by glycemic status, with a more pronounced inverse association among participants with normoglycemia.

Background/Objective: Acinetobacter baumannii is an opportunistic pathogen responsible for various healthcare-associated infections, particularly in critically ill patients. The emergence and rapid spread of multidrug- and extensively drug-resistant strains, notably carbapenem-resistant A. baumannii (CRAB), threaten global health. We aimed to investigate the clonal distribution, antimicrobial resistance profiles, and resistance determinants of CRAB bloodstream isolates in Korean hospitals to identify emerging high-risk clones and their potential clinical impact. Methods: Sequence types (STs) were determined using the Oxford multilocus sequence typing scheme, and antimicrobial susceptibility profiles and resistance determinants were evaluated. Results: We analyzed 812 CRAB bloodstream isolates collected from nine South Korean tertiary hospitals between 2016 and 2020. The isolates were classified into 39 STs, with ST191 (n = 245) and ST369 (n = 192) being the most prevalent. Between 2016 and 2020, ST369 increased from 2.6% to 37.9%, while ST195, first detected in 2018 (0.5%), increased to 19.0%; however, ST191 declined from 45.2% to 19.0%. Most CRAB infections were hospital-acquired (91.6%, 744 of 812), predominantly affecting men aged ≥51 years, particularly the 71-80-year-olds. Resistance rates were ≥80% for ampicillin-sulbactam and ciprofloxacin. blaOXA-23 was detected in 807 isolates, confirming its central role in carbapenem resistance. ST195 exhibited higher resistance to minocycline (29.4%) than did the other STs. Conclusions: Dynamic clonal shifts and high antimicrobial resistance exist among CRAB isolates in Korean hospitals, with the rapid emergence of ST195 and ST369 increasing clinical challenges. Continuous epidemiological surveillance and targeted infection control measures are essential to control the spread of high-risk CRAB clones.

The Asian tiger mosquito (Aedes albopictus) is an important vector of arboviruses, including dengue, chikungunya, and Zika. Its rapid global expansion has been facilitated by climate change and human activities. Phylogenetic studies of Ae. albopictus have largely relied on mitochondrial cytochrome c oxidase subunit 1 (COX1) and NADH dehydrogenase subunit 5 (ND5) markers, while the utility of cytochrome b (CYTB) remains underexplored. We collected Ae. albopictus from 13 sites in seven provinces of South Korea and analyzed COX1, ND5, and CYTB sequences. Genetic diversity indices were calculated, and phylogenetic relationships were reconstructed using maximum-likelihood trees and haplotype networks with a dataset obtained from GenBank. COX1 revealed 46 haplotypes, including six novel variants, with the highest diversity in southern coastal regions such as Busan and Suncheon. ND5 showed limited variation, with only two haplotypes. CYTB revealed three haplotypes, including region-specific variants in Busan and Wonju, supporting its role as a complementary marker. The Busan haplotype H41 bridged domestic and international lineages, suggesting Busan as a likely entry point. This study demonstrates that integrating COX1, ND5, and CYTB improves the resolution of Ae. albopictus phylogeography in Korea and highlights the need for continued molecular surveillance to guide vector control strategies.

BackgroundThe prevalence of chronic hepatitis B (CHB) and C viruses (CHC) has been studied widely, but the burden of CHB and CHC coinfection (CHB/CHC) remains to be elucidated. This study investigated the 16-year trend in the disease burden in patients with CHB and/or CHC.MethodsThis analysis used a customized database from 2002 to 2020 obtained from the Korean National Health Insurance Service. Prevalence of CHB/CHC in patients with CHB and/or CHC was analyzed for each year, sex, and type of healthcare providers. Development of cirrhosis and hepatocellular carcinoma (HCC), and overall survival were evaluated.ResultsA total of 747,476 patients (male: 53.5%) were divided into three groups: CHB (593,962; 79.5%), CHC (129,049; 17.3%), and CHB/CHC (24,465; 3.3%). Regarding age distribution, most patients were in their 30s to 60s across all groups (76.5%). Compared to patients in CHB/CHC group, those in CHC had significantly lower incidence of cirrhosis (CHB/CHC vs. CHC, adjusted hazard ratio [aHR] = 0.893, 95% confidence interval [CI] = 0.864–0.922) and HCC (aHR = 0.847, 95% CI = 0.809–0.886). The CHB and CHC groups had a lower risk of mortality compared to the CHB/CHC group. (CHB/CHC vs. CHB and CHC, aHR = 0.878 and 0.892, 95% CI = 0.852–0.905 and 0.864–0.922, respectively). CHB/CHC groups showed the highest average direct medical costs ($21,311) to HCC diagnosis compared to CHB ($19,685) and CHC ($17,650).ConclusionsCHB/CHC is burdensome in its disease progression risk and medical costs compared to monoinfection. An effective screening strategy for early management of CHB/CHC is warranted for public health in South Korea.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-025-11666-z.

The transcription of the HIV-1 long-terminal repeat (LTR), driven by the viral transactivator Tat, represents a distinct and druggable step in HIV-1 replication. Targeting Tat-mediated transcription is a promising antiretroviral strategy due to its mechanistic distinction from host cell transcription, although specificity remains a challenge due to potential off-target effects. To identify selective inhibitors, a two-step screening approach was employed. A time-resolved fluorescence resonance energy transfer (TR-FRET) assay was first used to identify compounds that disrupt Tat-trans-activation response (TAR) RNA interactions, yielding 655 initial hits, including five 2-phenyl acrylate derivatives with >50% inhibition. A secondary library of 194 structurally related compounds was then screened using a dual-luciferase reporter assay to evaluate transcriptional inhibition and cytotoxicity. From this, 46 compounds met selection criteria (>50% F-Luc inhibition, > 90% R-Luc activity, > 90% viral inhibition, and >70% cell viability). Among them, methyl (E)-2-(2-((4-(decyloxy)phenoxy)methyl)phenyl)-3-methoxyacrylate showed the highest potency, with IC50 and EC50 values of 1.44 and 0.83 μM, respectively. Time-of-addition (TOA) assays indicated inhibition of the Tat-dependent transcription phase. Surface plasmon resonance analysis revealed binding to the Tat peptide but not to TAR RNA, suggesting the binding target for 019854-B06. Immunoblotting and coimmunoprecipitation showed that 019854-B06 neither promotes Tat degradation nor disrupts the Tat/CycT1 complex, supporting a Tat-centric, nondegradative mechanism. Therefore, this study identifies a novel 2-phenyl acrylate-based inhibitor of Tat-mediated HIV-1 transcription through an integrated biophysical and functional screening strategy.

Patients recovering from post-coronavirus disease 2019 (COVID-19) often experience cognitive dysfunction, including difficulties with focusing, conversation, or memory issues, which can persist for weeks or even months after infection. Although the persistence of the SARS-CoV-2 spike protein has been reported in both the brain and serum, and is thought to potentially contribute to the long-term effects of SARS-CoV-2 infection on the brain, the underlying mechanisms leading to cognitive dysfunction remain unclear. This study investigates the molecular mechanisms by which the SARS-CoV-2 S1 protein (hereafter S1) induces cognitive impairment and explores the therapeutic potential of metformin in mitigating these effects. We demonstrate that intranasally administered S1 quickly entered the hippocampus and was associated with cognitive impairment by 6 weeks post-injection. Transcriptomic analysis of hippocampal tissue revealed early alterations in gene expression associated with synaptic function. We observed that the expression of hypoxia-responsive genes was also altered, suggesting the involvement of HIF-1α signaling. Further analysis confirmed that S1 stabilized the HIF-1α protein in a hypoxia-independent manner, and siRNA-mediated knockdown of HIF-1α restored synaptic gene expression, including GRIN2A, SHANK1, and JPH3. By 6 weeks post-injection, hippocampal neuronal loss was accompanied by the accumulation of phosphorylated tau (p-tau) and aggregated α-synuclein. Notably, treatment with metformin rescued synaptic gene expression and attenuated p-tau and α-synuclein aggregation. These findings suggest that S1 disrupts synaptic homeostasis and promotes neurodegenerative processes, and that metformin may serve as a potential therapeutic strategy to mitigate long-term cognitive sequelae of COVID-19.

The association of obstructive sleep apnea (OSA) with risk of incident cerebral microbleeds (CMBs) is unknown. To investigate the association between OSA severity and risk of incident CMBs in the late middle-aged general population. This cohort study included eligible participants who had in-home overnight polysomnography data and brain magnetic resonance imaging done at baseline (2011-2014) and 4-year follow-ups (first follow-up, 2015-2018, and second follow-up, 2019-2022) from an ongoing longitudinal cohort study of a Korean community of adults. Data were analyzed from March 2024 through January 2025. OSA severity was categorized by apnea-hypopnea index levels as no OSA (0-4.9 events/h), mild OSA (5.0-14.9 events/h), and moderate to severe OSA (≥15.0 events/h). CMBs were defined as well-defined focal areas (<10 mm in diameter) of very low signal intensity on gradient echo T2*-weighted images. Modified Poisson regression (robust error variance) was used to estimate relative risk (RR), with 95% CIs, of incident CMBs by OSA group; adjustment was done for age, sex, education level, body mass index, physical activity level, smoking and drinking status, total and low-density lipoprotein cholesterol level, hypertension, diabetes, age-related white matter changes, change in apnea-hypopnea index level, change in body mass index, and mean arterial pressure of the corresponding follow-up. Of 1441 study participants (mean [SD] age, 57.75 [5.53] years; 759 female [52.67%]), 436 participants (30.25%) and 193 participants (13.39%) had mild and moderate to severe OSA at baseline, respectively; 812 participants had no OSA. The cumulative incidence rate of CMBs in non-OSA, mild OSA, and moderate to severe OSA groups was 15 participants (1.85%), 7 participants (1.61%), and 9 participants (4.66%), respectively, at 4 years and 27 participants (3.33%), 14 participants (3.21%), and 14 participants (7.25%), respectively, at 8 years. In multivariable modified Poisson models, participants with moderate to severe OSA compared with the non-OSA group had an increased risk of developing CMBs at 8 years (RR, 2.14; 95% CI, 1.08-4.23; P = .02). These results were unaffected by the presence or absence of APOE-ε4 carrier status. No significantly increased risks were observed at 4 years or in the mild OSA group at any time. In this study, moderate to severe OSA was independently associated with an increased risk of incident CMBs over an 8-year follow-up. These results add to the evidence for the importance of sleep apnea to brain health.

BackgroundThe major drawback of a cohort study design is the loss to follow-up, which increases selection bias and threatens external validity, particularly in online surveys. It is important to identify factors beyond population or demographics that influence nonresponse rates in cohort studies.ObjectiveThis study aimed to examine the nonresponse rate and associated factors over a 10-year follow-up period among female participants in the Korea Nurses’ Health Study using data from the initial and subsequent surveys.MethodsThe Korea Nurses’ Health Study recruited 20,613 female nurses in 2013 using simple random sampling. The participants were followed up 10 times through 2022. We identified the demographic, work-related, survey-related, and psychological characteristics of nonresponding nurses during the 10-year follow-up and compared them with those who continued to participate. Descriptive statistics, chi-square tests, and multivariate logistic regression models were used for the analysis.ResultsThe nonresponse rate of the follow-up surveys from the 2nd to the 11th survey varied between 25.5% (5258/20,613; second survey) and 61.2% (12,620/20,613; sixth survey). The influence of age, education, and the usability of survey websites on nonresponse lasted up to the 11th survey. Nurses in their 20s were less likely to respond to the follow-up surveys than those in their 30s. Those who had an associate degree and neutral feelings about the usability of the survey websites were less likely to respond to the follow-up surveys than those who were satisfied with the initial survey. The influence of geographical region, hospital size, and psychological factors—including stress, fatigue, and sleep disturbance—was evident from the second to the sixth survey.ConclusionsWhen designing and recruiting female nurse participants for community-based cohort studies, researchers should consider the factors that influence nonresponse and adopt tailored strategies based on demographic characteristics. In addition, improving the usability of survey websites is recommended to reduce nonresponses at follow-up in cohort studies involving female participants.International Registered Report Identifier (IRRID)RR2-DOI: https://doi.org/10.4178/epih.e2024048

The Marburg virus (MARV) is a zoonotic pathogen that causes a high case fatality rate of up to 100% in humans. In response to Marburg virus disease (MVD) outbreaks in the Kagera region, an ecological investigation was initiated to map the population and ecological threat to the reservoir host of MARV: Egyptian fruit bats. The investigation conducted from October 2023 to December 2024 included interviews with local authorities to locate all known autochthonous bat colonies in the region. Bat species confirmation was performed using high-resolution melting analysis (HRMA) and DNA barcoding, targeting two mitochondrial genes: cytochrome oxidase 1 (COI) and 16S rRNA. We found five considerably large cave-dwelling Egyptian fruit bat colonies (with approximately 100,000 individuals) at the geolocations between 1°06′04.2″ and 2°26′35.8″ S latitude and 30°40′49.7″ and 31°51′19.8″ E longitude. The study also provides the first confirmed identification of Egyptian fruit bats (Rousettus aegyptiacus) (accession numbers: PV700530-PV700534) in major bat colonies in the Kagera River Basin ecosystem. Cave-dwelling Egyptian fruit bats in mines face higher risks, and thus, attention is needed to prevent this species from becoming more vulnerable to extinction. The loss of bat roosting sites and subsequent population declines are primarily driven by the destructive practice of burning car tyres and logs, a method used to eliminate colonies through toxic smoke and heat. The collection of guano and partially eaten fruits in mining caves, as well as daily contact with Egyptian fruit bats in mines, homes, and churches, have become major potential risk factors for MARV transmission to humans. Increased threats to bats in the Kagera region warrant the implementation of conservation strategies that ensure the survival of the bat populations and inform policies on MVD risk reduction in Tanzania and the broader East African region.