3D hepatic organoid production from human pluripotent stem cells.

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.

Realistic Estimation of COVID-19 Infection by Seroprevalence Surveillance of SARS-CoV-2 Antibodies: An Experience From Korea Metropolitan Area From January to May 2022.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, leading to the coronavirus disease 2019 (COVID-19) pandemic. Because a significant proportion of the COVID-19 confirmed cases were concentrated in the capital metropolitan area of South Korea, and a large proportion of the population in the area had been adequately vaccinated against COVID-19, we conducted a seroprevalence surveillance study focusing on the residents of the capital metropolitan area in South Korea. METHODS: We used a quota-sampling method to obtain blood samples from 1,000 individuals per round, equally stratified across seven age categories and sexes and regions, from five medical institutions located within the capital metropolitan area of South Korea. During five consecutive months (rounds) between January 2022 and May 2022, a total of 5,000 samples were analyzed for anti-spike (S) and anti-nucleocapsid (N) antibodies. RESULTS: High anti-S seropositivity was observed in all age groups, which corresponded to the vaccine coverage during the study period. Both the cumulative incidence based on polymerase chain reaction (PCR) and the estimated seroprevalence based on anti-N seropositivity increased in the fourth and fifth rounds, which corresponded to April 2022 and May 2022. Seroprevalence coincided with the cumulative incidence during the first three rounds, but exceeded from the fourth survey onwards when infection with omicron variants was increased rapidly in Korea. CONCLUSION: Seroprevalence confirmed the number of infection cases outside of PCR testing-based surveillance. Seroepidemiological surveillance can help us understand vaccine responses and detect hidden infections, thereby providing appropriate public health guidance for achieving population-level immunity.

Permissive epigenomes endow reprogramming competence to transcriptional regulators.

Identifying molecular and cellular processes that regulate reprogramming competence of transcription factors broadens our understanding of reprogramming mechanisms. In the present study, by a chemical screen targeting major epigenetic pathways in human reprogramming, we discovered that inhibiting specific epigenetic roadblocks including disruptor of telomeric silencing 1-like (DOT1L)-mediated H3K79/K27 methylation, but also other epigenetic pathways, catalyzed by lysine-specific histone demethylase 1A, DNA methyltransferases and histone deacetylases, allows induced pluripotent stem cell generation with almost all OCT factors. We found that simultaneous inhibition of these pathways not only dramatically enhances reprogramming competence of most OCT factors, but in fact enables dismantling of species-dependent reprogramming competence of OCT6, NR5A1, NR5A2, TET1 and GATA3. Harnessing these induced permissive epigenetic states, we performed an additional screen with 98 candidate genes. Thereby, we identified 25 transcriptional regulators (OTX2, SIX3, and so on) that can functionally replace OCT4 in inducing pluripotency. Our findings provide a conceptual framework for understanding how transcription factors elicit reprogramming in dependency of the donor cell epigenome that differs across species.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

Reprogramming progressive cells display low CAG promoter activity.

There is wide variability in the propensity of somatic cells to reprogram into pluripotency in response to the Yamanaka factors. How to segregate these variabilities to enrich for cells of specific traits that reprogram efficiently remains challenging. Here we report that the variability in reprogramming propensity is associated with the activity of the MKL1/SRF transcription factor and concurs with small cell size as well as rapid cell cycle. Reprogramming progressive cells can be prospectively identified by their low activity of a widely used synthetic promoter, CAG. CAGlow cells arise and expand during cell cycle acceleration in the early reprogramming culture of both mouse and human fibroblasts. Our work illustrates a molecular scenario underlying the distinct reprogramming propensities and demonstrates a convenient practical approach for their enrichment.

Respiratory Syncytial Virus Outbreak Without Influenza in the Second Year of the Coronavirus Disease 2019 Pandemic: A National Sentinel Surveillance in Korea, 2021-2022 Season.

BACKGROUND: This study aimed to investigate whether respiratory syncytial virus (RSV) and influenza virus (IFV) infections would occur in 2021-2022 as domestic nonpharmaceutical interventions (NPIs) are easing. METHODS: Data were collected from the Korean Influenza and Respiratory Virus Monitoring System database. The weekly positivity rates of respiratory viruses and number of hospitalizations for acute respiratory infections were evaluated (January 2016-2022). The period from February 2020 to January 2022 was considered the NPI period. The autoregressive integrated moving average model and Poisson analysis were used for data analysis. Data from 14 countries/regions that reported positivity rates of RSV and IFV were also investigated. RESULTS: Compared with the pre-NPI period, the positivity and hospitalization rates for IFV infection during 2021-2022 significantly decreased to 0.0% and 1.0%, respectively, at 0.0% and 1.2% of the predicted values, respectively. The RSV infection positivity rate in 2021-2022 was 1.8-fold higher than that in the pre-NPI period at 1.5-fold the predicted value. The hospitalization rate for RSV was 20.0% of that in the pre-NPI period at 17.6% of the predicted value. The re-emergence of RSV and IFV infections during 2020-2021 was observed in 13 and 4 countries, respectively. CONCLUSION: During 2021-2022, endemic transmission of the RSV, but not IFV, was observed in Korea.

Impact of Nonpharmaceutical Interventions on the Incidence of Respiratory Infections During the Coronavirus Disease 2019 (COVID-19) Outbreak in Korea: A Nationwide Surveillance Study.

BACKGROUND: Many countries have implemented nonpharmaceutical interventions (NPIs) to slow the spread of coronavirus disease 2019 (COVID-19). We aimed to determine whether NPIs led to the decline in the incidences of respiratory infections. METHODS: We conducted a retrospective, ecological study using a nationwide notifiable diseases database and a respiratory virus sample surveillance collected from January 2016 through July 2020 in the Republic of Korea. Intervention period was defined as February-July 2020, when the government implemented NPIs nationwide. Observed incidences in the intervention period were compared with the predicted incidences by an autoregressive integrated moving average model and the 4-year mean cumulative incidences (CuIs) in the same months of the preintervention period. RESULTS: Five infectious diseases met the inclusion criteria: chickenpox, mumps, invasive pneumococcal disease, scarlet fever, and pertussis. The incidences of chickenpox and mumps during the intervention period were significantly lower than the prediction model. The CuIs (95% confidence interval) of chickenpox and mumps were 36.4% (23.9-76.3%) and 63.4% (48.0-93.3%) of the predicted values. Subgroup analysis showed that the decrease in the incidence was universal for chickenpox, while mumps showed a marginal reduction among those aged <18 years, but not in adults. The incidence of respiratory viruses was significantly lower than both the predicted incidence (19.5%; 95% confidence interval, 11.8-55.4%) and the 4-year mean CuIs in the preintervention period (24.5%; P < .001). CONCLUSIONS: The implementation of NPIs was associated with a significant reduction in the incidences of several respiratory infections in Korea.

Decrease in hospital admissions for respiratory diseases during the COVID-19 pandemic: a nationwide claims study.

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively.

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling.

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.

Modelling monogenic autism spectrum disorder using mouse cortical organoids.

Variants of the contactin-associated protein-like 2 (CNTNAP2), which is a member of the neurexin family of proteins, function as cell adhesion molecules. The loss of CNTNAP2 function leads to autism spectrum disorder in humans and to autistic behaviours in mice. However, the functional effects of these mutations at the cellular level during fetal developmental periods remain elusive. Here, we studied mouse cortical organoids (mCOs) derived from Cntnap2-/- (knockout, KO) mouse induced pluripotent stem cells (miPSCs). Our results showed that KO mCOs displayed inhibitory-neuron-specific defects. At the neural progenitor stage, the GABAergic-neurogenesis-governing transcriptional network was dysregulated in the absence of Cntnap2. Our findings suggest that, in the early fetal cortical development, the cell adhesion molecule Cntnap2 plays a crucial role in the regulation of the differentiation of GABAergic neurons in the organoid platform. The reduced number of GABAergic neurons was efficiently restored in KO mCOs by treatment with the antiepileptic drug retigabine, showing the effectiveness of Cntnap2 KO mCOs in the therapeutic targeting of ASD.

Impacts of ambient air pollution on glucose metabolism in Korean adults: a Korea National Health and Nutrition Examination Survey study.

BACKGROUND: Exposure to air pollution was reported to affect glucose metabolism, increasing the risk of diabetes mellitus. We conducted an epidemiological study on glucose metabolism and air pollution by exploring the levels of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with changes in ambient air quality, depending on the characteristics of the susceptible population. METHODS: We carried out a cross-sectional analysis of a nationally representative sample of 10,014 adults (4267 in male and 5747 in female) from the Korea National Health and Nutrition Examination Survey in 2012 and 2013 along with data from the Korean Air Quality Forecasting System. The analysis was performed using a generalized linear model stratified by sex, age, and presence of diabetes. We assessed the changes in FBG and HbA1c associated with exposures to particulate matter (PM10), fine particulate matter (PM2.5), and nitrogen dioxide (NO2) after controlling for confounders. RESULTS: There were 1110 participants with diabetes (557 in male and 553 in female). Overall, the FBG level increased by 7.83 mg/dL (95% confidence interval [CI]: 2.80-12.87) per interquartile range (IQR) increment of NO2, 5.32 mg/dL (95% CI: 1.22-9.41) per IQR increment of PM10 at a moving average of 0-6 days, and 4.69 mg/dL (95% CI: 0.48-8.91) per IQR increment of PM2.5 at a moving average of 0-5 days. HbA1c increased by 0.57% (95% CI: 0.04-1.09) per IQR increment of PM10 at a moving average of 0-60 days and 0.34% (95% CI: 0.04-0.63) per IQR increment of PM2.5 at a moving average of 0-75 days. The change in FBG and HbA1c increased more in the diabetic group, especially in males aged 65 years or more. There was a strong association between elevation in diabetes-related parameters and exposure to air pollution. CONCLUSIONS: Our study provides scientific evidence supporting that short- and mid-term exposure to air pollution is associated with changes in biological markers related to diabetes. This finding suggests that the impact of air pollution should be reflected in chronic disease management when establishing local health care policies.

Spectrum of susceptibility to air quality and weather in individual children with atopic dermatitis.

BACKGROUND: Exposure to air pollution aggravates symptoms of atopic dermatitis (AD) in children in the population studies. Variability in individual patient's response from individual susceptibility is needed to be explored. OBJECTIVE: This study aimed to investigate spectrum of individual variability in the associations between AD symptoms and air quality. METHODS: We enrolled 89 children aged 0-6 years with AD (22 890 person-days). Daily manifestation of symptoms was recorded for an average of 257 days (range 100-499). Both an individual analysis using logistic regression models and an overall analysis using a generalized estimating equation were performed. RESULTS: The odds ratios of an individual ranged 0.24-8.11 for particulate matter <10 µm in diameter (PM10 ), 0.09-101.92 for nitrogen oxide (NO2 ), 0.03-44.00 for ozone (O3 ), 0.11-58.30 for sulfur dioxide (SO2 ), 0.00-15.83 for carbon monoxide (CO), 0.00-39 446.94 for temperature, and 0.03-5.18 for relative humidity, demonstrating a wide individual variability. In the overall analysis, PM10 , NO2 , SO2 , and CO had a significantly positive association, whereas temperature and relative humidity were negatively associated with AD symptoms. Air pollution was responsible for aggravation of symptoms from 24.7% (O3 ) to 39.3% (SO2 ) of AD children. Overall, 71.9% of the AD children responded to at least one or more air pollution and weather variable. CONCLUSION: Responses of AD children to air pollution and weather variable were considerably variable among individuals. An individualized model would be useful to forecast and manage AD symptoms in patients.

Epidemiologic Trends and Seasonality of Scabies in South Korea, 2010-2017.

Scabies is a parasitic skin infection with intense itching. Scabies infection seriously impairs quality of life, while outbreaks in medical institutions cause financial losses. This study aimed to present the annual and seasonal trend of prevalence of scabies in the national population. Scabies cases were extracted from National Health Insurance Service database and its epidemiologic characteristics were assessed. To analyze the seasonality of scabies occurrence, temperature and humidity were included in the model as weather factors, and the per capita gross national income index was adjusted. The annual prevalence by age group was 0.56-0.69 per 1,000 persons until the age of 40 years and peaked at 3.0-4.1 per 1,000 persons in the age group over 80 years. The number of women diagnosed with scabies has been consistently higher compared to that of men since 2010. Mean number of cases diagnosed as scabies was lowest in spring, approximately 4,000 cases, when the average temperature was less than 5°C at 2 months prior, whereas more than 6,000 scabies cases occurred in autumn when temperatures exceeded 25°C at 2 months prior. This study presents the epidemiological characteristics and seasonality of all cases nationwide over 8 years and will help to establish control policies.

Increasing Number of Scarlet Fever Cases, South Korea, 2011-2016.

The increasing number of reported scarlet fever cases during 2011‒2016 in the National Notifiable Infectious Disease database in South Korea occurred because of increased overall reporting and expanded reporting criteria rather than because of increasing scarlet fever incidence. Further increases are anticipated because of other expansions in reporting requirements.

The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma.

INTRODUCTION: Mild hyperthermia has been known to enhance the response of tumours to radiotherapy or chemotherapy by increasing tumour blood flow, thereby increasing tumour oxygenation or drug delivery. The purpose of this study was to assess the changes in temperature and blood flow in human cervical cancer in response to regional heating with modulated electro-hyperthermia (mEHT). METHODS: The pelvic area of 20 patients with cervical carcinoma was heated with mEHT. The peri-tumour temperature was measured using an internal organ temperature probe. The tumour blood flow was measured using 3D colour Doppler ultrasound by determining the peak systolic velocity/end-diastolic velocity ratio (S/D ratio) and the resistance index (RI) within blood vessels. RESULTS: The mean peri-tumour temperature was 36.7 ± 0.2 °C before heating and increased to 38.5 ± 0.8 °C at the end of heating for 60 min. The marked declines in RI and S/D values strongly demonstrated that heating significantly increased tumour blood perfusion. CONCLUSIONS: Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.

The Disease Burden of Lung Cancer Attributable to Residential Radon Exposure in Korean Homes.

BACKGROUND: Residential radon exposure is known to be an important risk factor for the development of lung cancer. The objective of this study was to calculate the disease burden of lung cancer attributable to residential radon exposure in Korea. METHODS: We calculated the national exposure level using Korean national radon survey data from 2011 to 2014, and house structure distribution data from each administrative region. Using the exposure-risk function, the population attributable fraction (PAF) was calculated and applied to calculate the disease burden for lung cancer attributable to residential radon exposure. RESULTS: Residential radon exposure levels were the highest, at 116.4 ± 50.4 Bq/m3 (annual mean radon concentration ± standard deviation) in detached houses, followed by 74.1 ± 30.0 Bq/m3 in the multi-family dwellings, and 55.9 ± 21.1 Bq/m3 in apartments. The PAF for lung cancer, due to long-term radon exposure in Korean homes, was 6.6% and 4.7% in men and women, respectively. The total disease burden of lung cancer attributable to residential radon exposure was 14,866 years of life lost (YLL) and 1,586 years lost due to disability (YLD) in 2013. Overall, 1,039 deaths occurred due to residential radon exposure, of which 828 were in men and 211 in women. CONCLUSION: The smoking rate of men in Korea exceeded 70% in the 1990s, and is still near 40%. Although the size of the effect varies depending on the estimation method, it is a critical aspect as a risk factor of lung cancer because of the synergistic relationship between smoking and radon exposure. Because the Korean society is rapidly aging, population who were formerly heavy-smokers are entering a high-risk age of lung cancer. Therefore, it is necessary to inform the public about the health benefits of reduced radon exposure and to strengthen the risk communication.

Burden of Disease Attributable to Inadequate Drinking Water, Sanitation, and Hygiene in Korea.

BACKGROUND: Diarrheal and intestinal infectious disease caused by inadequate drinking water, sanitation, and hygiene (WASH) is not only a great concern in developing countries but also a problem in low-income populations and rural areas in developed countries. In this study, we assessed the exposure to inadequate WASH in Korea and estimated the burden of disease attributable to inadequate WASH. METHODS: We used observational data on water supply, drinking water, sewage treatment rate, and hand washing to assess inadequate WASH conditions in Korea, and estimated the level of exposure in the entire population. The disease burden was estimated by applying the cause of death data from death registry and the morbidity data from the national health insurance to the population attributable fraction (PAF) for the disease caused by inappropriate WASH. RESULTS: In 2013, 1.4% of the population were exposed to inadequate drinking water, and 1.0% were living in areas where sewerage was not connected. The frequency of handwashing with soap after contact with excreta was 23.5%. The PAF due to inadequate WASH as a cluster of risk factors was 0.353 (95% confidence interval [CI], 0.275-0.417), among which over 90% were attributable to hand hygiene factors that were significantly worse than those in American and European high-income countries. CONCLUSION: The level of hand hygiene in Korea has yet to be improved to the extent that it shows a significant difference compared to other high-income countries. Therefore, improving the current situation in Korea requires a continuous hand washing campaign and a program aimed at all people. In addition, continuous policy intervention for improvement of sewage treatment facilities in rural areas is required, and water quality control monitoring should be continuously carried out.

Estimation of Cancer Incidence and Mortality Risks Attributed to Diagnostic Medical Radiation Exposure in Korea, 2013.

BACKGROUND: Radiation exposure from medical procedures has been rapidly increasing. We purposed to estimate the fraction of cancer incidence and mortality attributed to diagnostic medical radiation exposure in Korea. METHODS: Using information on diagnostic medical radiation exposure from various sources including national health examination (National Health Insurance Service), private health examination, and conscription health examination; the annual mean exposed organ dose (mGy) from all diagnostic medical radiation use, grouped by sex and 5-year age ranges up to 80 years, was calculated. Cancer incidence and mortality lifetime attributable risks (LARs) up to 85 years using estimated exposed organ doses and biological effects of ionizing radiation (BEIR) VII model (excess relative risk and excess absolute risk) were estimated. Using background cancer incidence and mortality risk based on the national database, along with estimated LARs, we finally estimated population attributable fraction (PAF) of cancer incidence and mortality. RESULTS: The PAF for diagnostic medical radiation exposure among all cancers of Koreans was 0.9% for incidence and mortality, resulting 1,915 cancer cases and 637 cancer deaths a year. The PAF in females was higher than those in males: 1.2% and 1.7% (incidence and mortality) versus 0.6% (same in incidence and mortality), respectively. CONCLUSION: The estimated PAF for diagnostic medical radiation in Korea in 2013 was higher than those reported in the UK in 2004. Optimized management of diagnostic medical radiation use is important in Korea.

Premature Deaths Attributable to Long-term Exposure to Ambient Fine Particulate Matter in the Republic of Korea.

BACKGROUND: Ambient fine particulate matter (PM2.5) is the major environmental health risk factor in Korea. Exposure to PM2.5 has been a growing public concern nationwide. With the rapid aging of the Korean population, the health effects attributable to long-term exposure to PM2.5 were expected to increase further in the future. We aimed to estimate premature deaths attributable to long-term exposure to ambient PM2.5 in Korea. METHODS: A modelled estimation of long-term exposure to PM2.5 was used to calculate the nationwide exposure level. Hazard ratios of long-term exposure to PM2.5 were obtained from a large prospective cohort study in North America. Modified cause of death (CoD) data, which applied the garbage code reclassification algorithm, were used to calculate premature deaths attributable to long-term exposure to PM2.5. RESULTS: From 1990 to 2013, the average population-weighted PM2.5 concentration in Korea was 30.2 µg/m3. The estimated number of premature deaths was 17,203 (95% confidence interval [CI], 11,056-22,772). The most common CoD was ischemic stroke (5,382; 3,101-7,403), followed by cancer of trachea, bronchus, and lung (4,958; 2,857-6,820), hemorrhagic stroke (3,452; 1,989-4,748), and ischemic heart disease (3,432; 1,383-5,358). CONCLUSION: Premature deaths due to long-term exposure to PM2.5 accounted for 6.4% of all deaths in Korea. However, individual efforts alone cannot prevent the effects of air pollution. This disease burden study can serve as a basis for the establishment of government policies and budgets and can be used to assess the effectiveness of environmental health policies.

The Burden of Acute Pesticide Poisoning and Pesticide Regulation in Korea.

BACKGROUND: This study aimed to estimate the burden of acute pesticide poisoning and to determine its trend with recently implemented pesticide regulations. METHODS: Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) due to acute pesticide poisoning using the methods of the Global Burden of Disease Study 2013. The values of YLLs, YLDs, and DALYs were stratified by sex, age groups, intentionality of poisoning, and causative agents. RESULTS: From 2006 to 2014, DALYs decreased by 69% (from 69,550 to 21,742). The decreasing tendency of DALYs was especially marked from 2011. The total burden of acute pesticide poisoning was mainly caused by YLLs and intentional pesticide poisoning. The highest DALYs due to acute pesticide poisoning occurred in those in their 40s and 50s; however, the decreased rates of DALYs were higher in those aged 10-49 years than in those aged more than 50 years. Herbicides including paraquat contributed to the largest proportion of total DALYs. CONCLUSION: As this is the first study to quantify the burden of acute pesticide poisoning using DALYs, our results provide comprehensive evidence of the importance of using strict regulations to prevent public health hazards due to acute pesticide poisoning.