Publications by authors named "Kyung-Duk Min"

42 Publications

ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis.

Sci Rep 2021 Nov 29;11(1):23056. Epub 2021 Nov 29.

Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, 6-1 Kishibe- Shimmachi, Suita, Osaka, 564-8565, Japan.

Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin-proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated. Here, we report for the first time that SMAD9, but not the other SMADs, is ubiquitylated by the E3 ligase ASB2 and targeted for proteasomal degradation. ASB2, as well as Smad9, is conserved among vertebrates. ASB2 expression was specific to the cardiac region from the very early stage of cardiac differentiation in embryogenesis of mouse. Knockdown of Asb2 in zebrafish resulted in a thinned ventricular wall and dilated ventricle, which were rescued by simultaneous knockdown of Smad9. Abundant Smad9 protein leads to dysregulated cardiac differentiation through a mechanism involving Tbx2, and the BMP signal conducted by Smad9 was downregulated under quantitative suppression of Smad9 by Asb2. Our findings demonstrate that ASB2 is the E3 ligase of SMAD9 and plays a pivotal role in cardiogenesis through regulating BMP signalling.
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http://dx.doi.org/10.1038/s41598-021-02390-0DOI Listing
November 2021

Snakebites in Rural Areas of Brazil by Race: Indigenous the Most Exposed Group.

Int J Environ Res Public Health 2021 09 5;18(17). Epub 2021 Sep 5.

Institute of Collective Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro 21941-598, RJ, Brazil.

Animal stings are environmental hazards that threaten millions annually and cause a significant socioeconomic impact. Snakebite envenoming affects 2.7 million people globally every year, mostly the poorest and rural communities, with approximately 27,000 annual cases in Brazil. This study's objective is to identify the most exposed racial group for snakebites in rural areas of Brazil and analyze possible differences in the outcome of an accident. A retrospective epidemiological study was conducted using a database of rural snakebite cases from Brazil's Ministry of Health (2017). Descriptive analysis and a regression model were performed to examine the association of bad outcomes after a snakebite with several covariables. While mixed-race individuals presented the highest number of cases (61.79%), indigenous and white populations were the racial groups with the highest and lowest exposure rates (194.3 and 34.1 per 100,000 population, respectively). The fatality rate was 3.5 times higher in the indigenous population compared to the white population. In the multivariable model, the number of hours between the accident and health care received and the case classification suggested an association with a bad outcome. Snakebite is prominent in Brazil, particularly among indigenous groups. Antivenom is available in the Brazilian Health System; however, efforts need to be made for decentralization.
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http://dx.doi.org/10.3390/ijerph18179365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431164PMC
September 2021

The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Promotes Inflammation and Non-Ischemic Heart Failure in Mice.

Circ Res 2021 Sep 28;129(6):684-698. Epub 2021 Jul 28.

Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA (Y.Y., E.M.-Y., K.-D.M., N.C., A.H.P., H.O., K.H., H.D., M.A.E., M.S., Y.W., S.S., K.W.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409899PMC
September 2021

Elucidating the Local Transmission Dynamics of Highly Pathogenic Avian Influenza H5N6 in the Republic of Korea by Integrating Phylogenetic Information.

Pathogens 2021 Jun 2;10(6). Epub 2021 Jun 2.

Avian Influenza Research and Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea.

Highly pathogenic avian influenza (HPAI) virus is one of the most virulent and infectious pathogens of poultry. As a response to HPAI epidemics, veterinary authorities implement preemptive depopulation as a controlling strategy. However, mass culling within a uniform radius of the infection site can result in unnecessary depopulation. Therefore, it is useful to quantify the transmission distance from infected premises (IPs) before determining the optimal area for preemptive depopulation. Accordingly, we analyzed the transmission risk within spatiotemporal clusters of IPs using transmission kernel estimates derived from phylogenetic clustering information on 311 HPAI H5N6 IPs identified during the 2016-2017 epidemic, Republic of Korea. Subsequently, we explored the impact of varying the culling radius on the local transmission of HPAI given the transmission risk estimates. The domestic duck farm density was positively associated with higher transmissibility. Ring culling over a radius of 3 km may be effective for areas with high dense duck holdings, but this approach does not appear to significantly reduce the risk for local transmission in areas with chicken farms. This study provides the first estimation of the local transmission dynamics of HPAI in the Republic of Korea as well as insight into determining an effective ring culling radius.
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http://dx.doi.org/10.3390/pathogens10060691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230294PMC
June 2021

Dynamics of the COVID-19 epidemic in the post-vaccination period in Korea: a rapid assessment.

Epidemiol Health 2021 27;43:e2021040. Epub 2021 May 27.

Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Korea.

Objectives: Coronavirus disease 2019 (COVID-19) has had a tremendous impact on public health and socioeconomic conditions globally. Although non-pharmaceutical interventions (NPIs) such as social distancing effectively reduced the incidence of COVID-19, especially in Korea, demand for vaccination has increased to minimize the social costs of NPIs. This study estimated the potential benefits of COVID-19 vaccination in Korea.

Methods: A mathematical model with vaccinated-susceptible-latent-infectious-recovered compartments was used to simulate the COVID-19 epidemic. The compartments were stratified into age groups of 0-19 years, 20-59 years, and 60 years or older. Based on the Korea Disease Control and Prevention Agency national vaccination plan for the second quarter of 2021, announced on March 15, we developed vaccination scenarios (with 150,000 dose/d and 100% compliance as the main scenario). Comparing scenarios without vaccination or with higher/lower vaccination rates and compliance, we estimated the numbers of COVID-19 cases that will be prevented by vaccination.

Results: The results projected 203,135 cases within a year after April 2021 without vaccination, which would be reduced to 71,248 (64.9% decrease) by vaccination. Supposing a vaccination rate of 150,000 dose/d and 100% compliance, social distancing interventions for those aged 20 or more can be retracted after January 1, 2022.

Conclusions: We expect COVID-19 vaccination to be effective in Korea. Health authorities should minimize delays in vaccination and vaccine avoidance to maximize the effectiveness of vaccination and end social distancing early.
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http://dx.doi.org/10.4178/epih.e2021040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289478PMC
July 2021

Comparative Evaluation of Growth Performance between Bivalent and Trivalent Vaccines Containing Porcine Circovirus Type 2 (PCV2) and in a Herd with Subclinical PCV2d Infection and Enzootic Pneumonia.

Vaccines (Basel) 2021 May 3;9(5). Epub 2021 May 3.

Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea.

The present field trial compared two combined vaccines of porcine circovirus type 2 (PCV2) and , each administered in herd with subclinical PCV2d infection and enzootic pneumonia. One vaccine was a bivalent containing PCV2a and and the other was a trivalent vaccine containing PCV2a and 2b (PCV2a/b), and . The defining difference between these two vaccines was the inclusion or absence of PCV2b antigen. A total of 480, 21day-old pigs were randomly allocated to one of four treatment groups (120 pigs per group, male = 60 and female = 60). These groups included; one-dose trivalent-vaccinated, two-dose trivalent-vaccinated, one-dose bivalent-vaccinated, and unvaccinated. The one- and two-dose trivalent vaccinated pigs exhibited significantly better growth performance when compared with those vaccinated with the bivalent vaccine. The one- and two-dose trivalent vaccinated pigs also reduced the amount of PCV2d loads in the blood and feces, and resulted in a lower load in the larynx when compared with one-dose bivalent vaccinated pigs. Statistical differences were not observed between the one- and two-dose trivalent-vaccinated groups in terms of growth performance, serology, amount of PCV2d loads in the blood and feces, amount of load in larynx, and pathological lesions. The results of the present study will provide swine practitioners and producer with comparative clinical field data to select the proper vaccine and vaccination regiment for herds suffering from subclinical PCV2d infection and enzootic pneumonia.
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http://dx.doi.org/10.3390/vaccines9050450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147604PMC
May 2021

Importance of clonal hematopoiesis in heart failure.

Trends Cardiovasc Med 2021 Apr 20. Epub 2021 Apr 20.

Berne Cardiovascular Research Center USA; Department of Cardiology USA; Hematovascular Biology Center, University of Virginia, School of Medicine, Charlottesville, VA, 22908 USA. Electronic address:

Heart failure is prevalent in the elderly population. Inflammatory processes can contribute to the progression of heart failure by altering the balance of tissue healing and pathological remodeling during the injury response. New findings show that aging can alter immune cell phenotypes through the process of clonal hematopoiesis. This condition results from acquired somatic DNA mutations in specific driver genes that give rise to clonal expansions of mutant hematopoietic cells with overactive inflammatory properties. Recent clinical and experimental studies have shown that clonal hematopoiesis is prevalent in heart failure patients and associated with poor prognosis. In this review, we summarize current evidence that associates clonal hematopoiesis with the progression of heart failure. We further describe the mechanistic links between clonal hematopoiesis and the pro-inflammatory responses that can contribute to pathological outcomes in the heart. Finally, we provide perspectives on future research directions in the area of clonal hematopoiesis and heart failure.
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http://dx.doi.org/10.1016/j.tcm.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526615PMC
April 2021

New assessment for residential greenness and the association with cortical thickness in cognitively healthy adults.

Sci Total Environ 2021 Jul 1;778:146129. Epub 2021 Mar 1.

Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea. Electronic address:

Background: Recent evidence suggests that neurological health could be improved with the intervention of local green space. A few studies adopted cortical thickness, as an effective biomarker for neurodegenerative disorder, to investigate the association with residential greenness. However, they relied on limited data sources, definitions or applications to assess residential greenness. Our cross-sectional study assessed individual residential greenness using an alternative measure, which provides a more realistic definition of local impact and application based on the type of area, and investigated the association with cortical thickness.

Methods: The study population included 2542 subjects who participated in the medical check-up program at the Health Promotion Center of the Samsung Medical Center in Seoul, Korea, from 2008 to 2014. The cortical thickness was calculated by each of the four and global lobes from brain MRI. For greenness, we used the enhanced vegetation index (EVI) that detects canopy structural variation by adjusting background noise based on satellite imagery data. To assess individual exposure to residential greenness, we computed the maximum annual EVI before the date of a medical check-up and averaged it within 750 m from subjects' homes to represent an average walking distance. Finally, we assessed the association with cortical thickness by urban and non-urban populations using multiple linear regression adjusting for individual characteristics.

Results: The average global cortical thickness and EVI were 3.05 mm (standard deviation = 0.1 mm) and 0.31 (0.1), respectively. An interquartile range increase in EVI was associated with 11 μm (95% confidence interval = 3-20) and 9 μm (1-16) increases in cortical thickness of the parietal and occipital regions among the urban population. We did not find associations in non-urban subjects.

Conclusions: Our findings confirm the association between residential greenness and neurological health using alternative exposure assessments, indicating that high exposure to residential greenness can prevent neurological disorders.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146129DOI Listing
July 2021

An exploration of the protective effect of rodent species richness on the geographical expansion of Lassa fever in West Africa.

PLoS Negl Trop Dis 2021 02 1;15(2):e0009108. Epub 2021 Feb 1.

Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.

Background: Lassa fever (LF) is one of the most devastating rodent-borne diseases in West Africa, causing thousands of deaths annually. The geographical expansion of LF is also a concern; cases were recently identified in Ghana and Benin. Previous ecological studies have suggested that high natural-host biodiversity reduces the likelihood of spillover transmission of rodent-borne diseases, by suppressing the activities of reservoir species. However, the association of biodiversity with the geographical expansion of LF has not been the subject of epidemiological studies.

Methodology/principal Findings: We conducted a spatial analysis based on sociodemographic, geographical, and ecological data, and found that higher rodent species richness was significantly associated with a lower risk of LF emergence in West Africa from 2008 to 2017 (Odds Ratio = 0.852, 95% Credible Interval = 0.745-0.971).

Conclusions/significance: The results reinforce the importance of the 'One Health' approach by demonstrating that a high level of biodiversity could benefit human health.
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http://dx.doi.org/10.1371/journal.pntd.0009108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877741PMC
February 2021

Overview of snakebite in Brazil: Possible drivers and a tool for risk mapping.

PLoS Negl Trop Dis 2021 01 29;15(1):e0009044. Epub 2021 Jan 29.

Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health of Brazil, Rio de Janeiro, RJ, Brazil.

Snakebite envenoming affects close to 2.7 million people globally every year. In Brazil, snakebites are reported to the Ministry of Health surveillance system and cases receive antivenom free of charge. There is an urgent need to identify higher risk areas for antivenom distribution, and to develop prevention activities. The objective of this study is to provide an overview of the epidemiological situation of snakebite envenoming in Brazil and explore possible drivers; as well as to create a flowchart tool to support decision-makers identify higher risk areas. An ecological-type study was carried out using data by municipality (2013-2017). Study parts: 1) Create a geocoded database and perform a descriptive and cluster analysis; 2) Statistical analysis to measure the association of snakebite and possible environmental and socioeconomic drivers; 3) Develop a flowchart to support decision-makers and the application of this tool in one state (Rio Grande do Sul) as an example. An average of 27,120 snakebite cases per year were reported at the country level. Clusters of municipalities with high numbers of snakebites are mostly found in the Amazon Legal Region. The negative binomial regression model showed association with the snakebite case count: the type of major habitat, tropical or non-tropical; temperature; percentage of urbanization; precipitation; elevation; GDP per capita; a weaker relation with forest loss; and with venomous snake richness. The state where the instrument was applied reported 4,227 snakebites in the period. Most municipalities were considered as medium risk and 56/496 as high risk according to the tool created. Snakebite cases are distributed across the entire country with the highest concentration in the Legal Amazon Region. This creates a complex situation both for better understanding of the association of environmental and socioeconomic factors with snakebites and for the distribution and maintenance of antivenom to remote areas. Research into types of antivenom with a longer shelf life without the need for refrigeration is needed.
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http://dx.doi.org/10.1371/journal.pntd.0009044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875335PMC
January 2021

Protective effect of predator species richness on human hantavirus infection incidence.

Sci Rep 2020 12 10;10(1):21744. Epub 2020 Dec 10.

Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, South Korea.

Are predators of rodents beneficial for public health? This question focuses on whether predators regulate the spillover transmission of rodent-borne diseases. No clear answer has emerged because of the complex linkages across multiple trophic levels and the lack of accessible data. Although previous empirical findings have suggested ecological mechanisms, such as resource partitioning, which implies protective effects from predator species richness, epidemiological evidence is needed to bolster these arguments. Thus, we investigated the association between predator species richness and incidence of rodent-borne haemorrhagic fever with renal syndrome in the human population using district-level longitudinal data of 13 years for South Korea. With the exception of districts with low species richness, we found a significant negative association between the incidence of haemorrhagic fever with renal syndrome and the species richness of both avian and mammalian predators; the trends for both predator types were similar. Thus, biodiversity conservation may benefit public health.
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http://dx.doi.org/10.1038/s41598-020-78765-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728771PMC
December 2020

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries.

Vaccine 2021 01;39(1):147-157

Merck & Co, Rahway, NJ, United States.

Objective: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model.

Methods: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY).

Results: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage.

Conclusion: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.
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http://dx.doi.org/10.1016/j.vaccine.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735375PMC
January 2021

Association between predator species richness and human hantavirus infection emergence in Brazil.

One Health 2021 Jun 13;11:100196. Epub 2020 Nov 13.

Institute of Health and Environment, Graduate School of Public Health, Seoul National University, South Korea.

Hantavirus infection is a rodent-borne disease (RBD) transmitted by urine or feces (as the natural reservoirs) with an annual estimated worldwide incidence of ~150,000 cases. Previous ecological studies suggested that higher species richness of rodents could decrease the risk of RBDs in humans, because the regulatory pressure of predators could reduce contact among rodents, and between humans and rodents. Using surveillance data, we investigated the association of predator species richness with hantavirus infection emergence in 5562 Brazilian inland municipalities between 2007 and 2017. Multivariable logistic regression models were used for the analyses. Diurnal and non-diurnal predator species were independent explanatory variables in the models. Rodent species richness and demographic, socioeconomic, and environmental factors were used as covariates. During the study period, 1084 cases were reported in 429 municipalities. The results showed a reverse-U-shaped association between diurnal predator species richness and hantavirus infection emergence (odds ratio [OR] 0.463, 0.688, and 0.553 for the first [lowest], third, and fourth [highest] quartiles, respectively, using the second quartile as a reference), while higher non-diurnal predator species richness tended to be associated with higher emergence risk (OR 0.134, 1.065, and 2.708 for the first, third, and fourth quartiles, respectively). The difference in these associations illustrates the complexity of the effects of predator species richness on human RBDs, which require further investigation in follow-up studies. The results showed a close link between environmental factors and public health, emphasizing that the One Health concept should be employed to understand the dynamics of RBDs.
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http://dx.doi.org/10.1016/j.onehlt.2020.100196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701261PMC
June 2021

The Relationship Between Dog-Related Factors and Owners' Attitudes Toward Pets: An Exploratory Cross-Sectional Study in Korea.

Front Vet Sci 2020 18;7:493. Epub 2020 Aug 18.

College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea.

In Korea, there is a need for research on human-animal relationships because of an increase in the number of companion animals and the positive changes in public perception toward them. Few studies have examined these changes. This epidemiological study investigates the characteristics of Korean dog owners and their pet dogs and identifies the owner- and dog-dependent factors that influence the owners' attitudes toward pets. We conducted a cross-sectional study of dog owners by asking them to complete a Pet Attitude Scale-based questionnaire about their dogs and themselves. The participants included 654 young adults between 19 and 39 years of age who lived in Seoul and owned dogs. We found that most dogs were owned by single, educated, high-income men who preferred small purebred dogs. Most were also likely to underestimate their dog's body condition score (BCS). The multivariable logistic regression (odds ratio, OR) and the multiple linear regression (unstandardized coefficients, ) models suggested that positive pet attitudes were associated with nine factors: overweight ( = 2.68, = 5.28) or a normal BCS ( = 2.09, = 5.58), having a medical history of related diseases ( = 2.36, = 6.38) and vaccination ( = 2.10, = 6.22), buying the pet dog ( = 0.60, = -3.85), having a small dog (≤10 kg) ( = 1.66), visiting the veterinarian frequently ( = 1.08, = 0.39), spending more time with the dog ( = 1.23, =1.32), and keeping other species in the house ( = -4.27). This study is the first to identify the relationships between owner- and dog-dependent factors and pet owner attitude toward pets, all within a Korean cultural context. This study highlights the factors associated with the development of relationships between pet dogs and their owners. The exploratory study is novel because it examines pet ownership in the context of the Korean culture; previous pet ownership studies were set in the West and are analyzed with Western cultural values in mind.
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http://dx.doi.org/10.3389/fvets.2020.00493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461997PMC
August 2020

Estimating the Effectiveness of Non-Pharmaceutical Interventions on COVID-19 Control in Korea.

J Korean Med Sci 2020 Sep 7;35(35):e321. Epub 2020 Sep 7.

Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Korea.

Background: The coronavirus disease 2019 (COVID-19) pandemic has posed significant global public health challenges and created a substantial economic burden. Korea has experienced an extensive outbreak, which was linked to a religion-related super-spreading event. However, the implementation of various non-pharmaceutical interventions (NPIs), including social distancing, spring semester postponing, and extensive testing and contact tracing controlled the epidemic. Herein, we estimated the effectiveness of each NPI using a simulation model.

Methods: A compartment model with a susceptible-exposed-infectious-quarantined-hospitalized structure was employed. Using the Monte-Carlo-Markov-Chain algorithm with Gibbs' sampling method, we estimated the time-varying effective contact rate to calibrate the model with the reported daily new confirmed cases from February 12th to March 31st (7 weeks). Moreover, we conducted scenario analyses by adjusting the parameters to estimate the effectiveness of NPI.

Results: Relaxed social distancing among adults would have increased the number of cases 27.4-fold until the end of March. Spring semester non-postponement would have increased the number of cases 1.7-fold among individuals aged 0-19, while lower quarantine and detection rates would have increased the number of cases 1.4-fold.

Conclusion: Among the three NPI measures, social distancing in adults showed the highest effectiveness. The substantial effect of social distancing should be considered when preparing for the 2nd wave of COVID-19.
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http://dx.doi.org/10.3346/jkms.2020.35.e321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476801PMC
September 2020

Comparative study of the virulence of 3 major Korean porcine circovirus type 2 genotypes (a, b, and d).

Can J Vet Res 2020 Jul;84(3):235-240

Department of Veterinary Pathology, College of Veterinary Medicine, (Cho, Kang, Oh, Yang, Park, Chae) and Institute of Health and Environment (Min), Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826, Seoul, Republic of Korea; College of Liberal Arts, Anyang University, Samdeok-ro 37, Beob-gil 22, Manan-gu, Anyang-si, Gyeonggi-Do, 14028, Republic of Korea (Ham).

The objective of this study was to compare the virulence of 3 major Korean porcine circovirus type 2 (PCV2) genotypes in terms of clinical signs, PCV2 viremia and antibody titers, lymphoid lesions, and PCV2-antigen within lymphoid lesions in experimentally infected pigs. Pigs were infected at 7 weeks with PCV2a, PCV2b, and PCV2d strains and necropsied at 28 days post-infection. No statistical differences were observed in clinical signs, PCV2 viremia and antibody titers, lymphoid lesions scores, and numbers of PCV2 antigens among the 3 major Korean PCV2 genotypes. The results of this study indicate that the 3 major Korean PCV2 genotypes, PCV2a, PCV2b, and PCV2d, have similar virulence.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301680PMC
July 2020

A modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine protects late-term pregnancy gilts against a heterologous PRRSV-2 challenge.

Can J Vet Res 2020 Jul;84(3):172-180

Department of Veterinary Pathology, College of Veterinary Medicine, (Yang, Cho, Oh, Park, Kang, Chae) and Institute of Health and Environment (Min), Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826, Seoul, Republic of Korea.

The objective of this study was to evaluate the efficacy of a modified-live virus (MLV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against a heterologous PRRSV-2 challenge in late-term pregnancy gilts under experimental conditions. Eighteen gilts were randomly assigned to vaccinated-challenged, unvaccinated-challenged, and unvaccinated-unchallenged groups ( = 6 gilts per group). Pregnant gilts in the vaccinated-challenged and unvaccinated-unchallenged groups were able to carry their pregnancies to full term and farrowed after 114 to 115 days of gestation. In contrast, pregnant gilts in the unvaccinated-challenged group did not reach full term and farrowed early, after 104 to 108 days of gestation. Pregnant gilts vaccinated with the PRRSV-2 MLV vaccine exhibited a reduction in PRRSV-2 viremia. At the time of challenge with PRRSV-2, vaccinated gilts had relatively low levels of neutralizing antibody titers (≤ 1:16 titer), whereas the number of interferon-γ-secreting cells (IFN-γ-SC) was consistently at protective levels (IFN-γ-SC, ≥ 150 per million). Induction of cell-mediated immunity, as measured by PRRSV-2-specific IFN-γ-SC, correlated with a reduction in PRRSV-2 viremia. Duration of immunity was a minimum of 19 wk. Taken together, the results presented here suggest that vaccination of gilts with a PRRSV-2 MLV vaccine can protect against a heterologous PRRSV-2 challenge and improve the reproductive performance of late-term pregnancy gilts.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301676PMC
July 2020

Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction.

JCI Insight 2020 03 26;5(6). Epub 2020 Mar 26.

Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

Clonal hematopoiesis of indeterminate potential is prevalent in elderly individuals and associated with increased risks of all-cause mortality and cardiovascular disease. However, mouse models to study the dynamics of clonal hematopoiesis and its consequences on the cardiovascular system under homeostatic conditions are lacking. We developed a model of clonal hematopoiesis using adoptive transfer of unfractionated ten-eleven translocation 2-mutant (Tet2-mutant) bone marrow cells into nonirradiated mice. Consistent with age-related clonal hematopoiesis observed in humans, these mice displayed a progressive expansion of Tet2-deficient cells in multiple hematopoietic stem and progenitor cell fractions and blood cell lineages. The expansion of the Tet2-mutant fraction was also observed in bone marrow-derived CCR2+ myeloid cell populations within the heart, but there was a negligible impact on the yolk sac-derived CCR2- cardiac-resident macrophage population. Transcriptome profiling revealed an enhanced inflammatory signature in the donor-derived macrophages isolated from the heart. Mice receiving Tet2-deficient bone marrow cells spontaneously developed age-related cardiac dysfunction characterized by greater hypertrophy and fibrosis. Altogether, we show that Tet2-mediated hematopoiesis contributes to cardiac dysfunction in a nonconditioned setting that faithfully models human clonal hematopoiesis in unperturbed bone marrow. Our data support clinical findings that clonal hematopoiesis per se may contribute to diminished health span.
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http://dx.doi.org/10.1172/jci.insight.135204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213793PMC
March 2020

Nitroglycerin Tolerance in Patients With ALDH2 Variant.

Circ J 2020 02 14;84(3):384-385. Epub 2020 Feb 14.

Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center.

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http://dx.doi.org/10.1253/circj.CJ-20-0049DOI Listing
February 2020

Association between exposure to traffic-related air pollution and pediatric allergic diseases based on modeled air pollution concentrations and traffic measures in Seoul, Korea: a comparative analysis.

Environ Health 2020 01 14;19(1). Epub 2020 Jan 14.

Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.

Background: Pediatric allergic diseases are a major public health concern, and previous studies have suggested that exposure to traffic-related air pollution (TRAP) exposure is a risk factor. These studies have typically assessed TRAP exposure using traffic measures, such as distance to major roads, or by modeling air pollutant concentrations; however inconsistent associations with pediatric allergic diseases have often been found. Using road proximity and density, we previously found an association between TRAP and atopic eczema among approximately 15,000 children living in Seoul, Korea, heavily populated and highly polluted city in which traffic is a major emission source. We aimed to conduct a parallel analysis using modeled air pollution concentrations and thus examine the consistency of the association. Specifically, we examined the associations of individual-level annual-average concentrations of NO, PM, and PM with symptoms and diagnoses of three pediatric allergic diseases including asthma, allergic rhinitis, and atopic eczema.

Methods: The study population included 14,614 children from the Seoul Atopy Friendly School Project Survey in Seoul, Korea, in 2010. To assess individual exposures to TRAP among these children, we predicted annual-average concentrations of NO, PM, and PM at the children's home addresses in 2010 using universal kriging and land use regression models along with regulatory air quality monitoring data and geographic characteristics. Then, we estimated odds ratios (ORs) of the three allergic diseases for interquartile increases in air pollution concentrations after adjusting for individual risk factors in mixed effects logistic regression.

Results: Symptoms and diagnoses of atopic eczema symptoms showed an association with NO (OR = 1.07, 95% confidence interval = 1.02-1.13; 1.08, 1.03-1.14) and PM (1.06, 1.01-1.12; 1.07, 1.01-1.13). ORs of PM were positive but not statistically significant (1.01, 0.95-1.07; 1.04, 0.98-1.10). No association was found between asthma and allergic rhinitis, although PM showed a marginal association with allergic rhinitis.

Conclusions: Our consistent findings regarding the association between TRAP and the prevalence of atopic eczema using traffic measures and surrogate air pollutants suggested the effect of TRAP on children's health. Follow-up studies should elucidate the causal link, to support subsequent policy considerations and minimize adverse health effects in children.
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http://dx.doi.org/10.1186/s12940-020-0563-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961284PMC
January 2020

-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure.

JACC Basic Transl Sci 2019 Oct 18;4(6):684-697. Epub 2019 Sep 18.

Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.

Janus kinase 2 (valine to phenylalanine at residue 617) ( ) mutations lead to myeloproliferative neoplasms associated with elevated myeloid, erythroid, and megakaryocytic cells. Alternatively these same mutations can lead to the condition of clonal hematopoiesis with no impact on blood cell counts. Here, a model of myeloid-restricted expression from lineage-negative bone marrow cells was developed and evaluated. This model displayed greater cardiac inflammation and dysfunction following permanent left anterior descending artery ligation and transverse aortic constriction. These data suggest that mutations arising in myeloid progenitor cells may contribute to cardiovascular disease by promoting the proinflammatory properties of circulating myeloid cells.
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http://dx.doi.org/10.1016/j.jacbts.2019.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834960PMC
October 2019

Owners' Attitudes toward Their Companion Dogs Are Associated with the Owners' Depression Symptoms-An Exploratory Study in South Korea.

Int J Environ Res Public Health 2019 09 24;16(19). Epub 2019 Sep 24.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea.

Various health benefits from the ownership of companion dogs have been studied from a One Health perspective. However, the preventive effects on depression are unclear, with inconsistent results across studies. We hypothesized that heterogeneity among owners would be related to the mixed results. Specifically, the difference in the strength of the bond between the owners and their companion dogs would modify the effect of dog ownership. As an exploratory study, we compared the depression symptoms of the owners with favorable attitudes toward their dogs, with those of the owners with unfavorable attitudes, to investigate the potential effect modification of owners' attitudes on the association between the ownership and depression symptom. We conducted a web-based questionnaire survey of 654 19- to 39-year-old adults who had companion dogs in Seoul, South Korea, where a major health burden is depression among young adults. We measured the owners' attitudes toward their dogs using the modified Pet Attitude Scale (PAS-M) and their depression symptoms using the short version of the Center for Epidemiologic Studies depression scale (CESD-10). Demographic and socioeconomic factors were measured to adjust for the association between attitude and depression symptoms. Multivariate logistic regression models were used in this study. The owners who had less favorable attitudes toward their dogs (lower PAS-M scores) tended to have depression symptoms. The direction and significance were maintained either when the PAS-M variable was used as a continuous variable (odds ratio (OR) for one score increase in PAS-M was 0.95 (95% confidence interval (CI) = 0.94-0.96)) or as a categorical variable (OR for lower PAS-M was 3.19 (95% CI = 2.28 -4.47)). We found a positive significant association between owners' depression symptoms and unfavorable attitudes toward their dogs, although causal direction could not be determined. Future studies should investigate the potential causal link.
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http://dx.doi.org/10.3390/ijerph16193567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801548PMC
September 2019

Spatial analysis to assess the relationship between human and bovine brucellosis in South Korea, 2005-2010.

Sci Rep 2019 04 30;9(1):6657. Epub 2019 Apr 30.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, South Korea.

The first case of human brucellosis in South Korea was reported in 2002, and cases of human infection continue to occur. Although an association between human and bovine brucellosis has been identified, the spatial relationship has not been studied in South Korea. Here, we analysed the spatial patterns of human and bovine brucellosis retrieved from the human and veterinary surveillance data, as well as the spatial correlation between human and bovine brucellosis and associated factors that contribute to its occurrence. The risk of human brucellosis was analysed using a Bayesian spatial model with potential risk factors. Our results show that, for both human and bovine brucellosis, hotspots were clustered in the southeast regions of Korea, whereas coldspots were clustered in the northwest regions of Korea. Our study suggests that the risk of human brucellosis increases in rural regions with the highest risk of bovine brucellosis. Collaborative strategies between human and veterinary health sectors (e.g, public health intervention and region-specific eradication programs for bovine brucellosis) would reduce the burden of brucellosis in South Korea.
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http://dx.doi.org/10.1038/s41598-019-43043-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491422PMC
April 2019

Deforestation Increases the Risk of Scrub Typhus in Korea.

Int J Environ Res Public Health 2019 04 29;16(9). Epub 2019 Apr 29.

Institute of Health and Environment, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.

: Scrub typhus is an important public health issue in Korea. Risk factors for scrub typhus include both individual-level factors and environmental drivers, and some are related to the increased density of vector mites and rodents, the natural hosts of the mites. In this regard, deforestation is a potential risk factor, because the deforestation-induced secondary growth of scrub vegetation may increase the densities of mites and rodents. To examine this hypothesis, this study investigated the association between scrub typhus and deforestation. : We acquired district-level data for 2006-2017, including the number of cases of scrub typhus reported annually, deforestation level, and other covariates. Deforestation was assessed using preprocessed remote-sensing satellite data. Bayesian regression models, including Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial models, were examined, and spatial autocorrelation was considered in hierarchical models. A sensitivity analysis was conducted using different accumulation periods for the deforestation level to examine the robustness of the association. : The final models showed a significant association between deforestation and the incidence of scrub typhus (relative risk = 1.20, 95% credible interval = 1.15-1.24). The sensitivity analysis gave consistent results, and a potential long-term effect of deforestation for up to 5 years was shown. : The results support the potential public health benefits of forest conservation by suppressing the risk of scrub typhus, implying the need for strong engagement of public health sectors in conservation issues from a One Health perspective.
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http://dx.doi.org/10.3390/ijerph16091518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539434PMC
April 2019

AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs.

Cardiovasc Drugs Ther 2019 06;33(3):277-286

Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Osaka, Suita, 565-8565, Japan.

Purpose: Several lines of evidence suggest that renal dysfunction is associated with cardiovascular toxicity through the action of uremic toxins. The levels of those uremic toxins can be reportedly reduced by the spherical carbon adsorbent AST-120. Because heart failure (HF) causes renal dysfunction by low cardiac output and renal edema, the removal of uremic toxins could be cardioprotective.

Method: To determine whether blood levels of the uremic toxin indoxyl sulfate (IS) increase in HF and whether AST-120 can reduce those levels and improve HF. We induced HF in 12 beagle dogs by 6 weeks of rapid right ventricular pacing at 230 beats per min. We treated six dogs with a 1-g/kg/day oral dosage of AST-120 for 14 days from week 4 after the start of rapid ventricular pacing. The other six dogs did not receive any treatment (control group).

Results: In the untreated dogs, IS levels increased as cardiac function deteriorated. In contrast, plasma IS levels in the treated dogs decreased to baseline levels, with both left ventricular fractional shortening and pulmonary capillary wedge pressure also improving when compared with untreated dogs. Finally, AST-120 treatment was shown to reduce both myocardial apoptosis and fibrosis along with decreases in extracellular signal-regulated kinase phosphorylation, the Bax/Bcl-2 ratio, and TGF-β1 expression and increases in AKT phosphorylation.

Conclusions: IS levels are increased in HF. AST-120 treatment reduces the levels of IS and improves the pathophysiology of HF in a canine model. AST-120 could be a novel candidate for the treatment of HF.
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http://dx.doi.org/10.1007/s10557-019-06875-zDOI Listing
June 2019

A dipeptidyl peptidase-IV inhibitor improves diastolic dysfunction in Dahl salt-sensitive rats.

J Mol Cell Cardiol 2019 04 14;129:257-265. Epub 2019 Mar 14.

Clinical Research and Development, National Cerebral and Cardiovascular Center, Osaka, Japan. Electronic address:

To date, there is no established treatment for heart failure with preserved ejection fraction (HFpEF). Dipeptidyl peptidase-IV (DPP-IV) inhibitors reportedly have improved not only diabetes mellitus but also heart failure with systolic dysfunction in experimental models. We investigated the effects of a DPP-IV inhibitor on HFpEF in rats. Dahl salt-sensitive rats were fed either high-salt (high-salt diet (HSD): 8% NaCl) or low-salt diets (0.3% NaCl) from 6.5 weeks of age. They were then treated with or without a DPP-IV inhibitor, vildagliptin (10 mg/kg/day, orally), from 11 weeks of age for 9 weeks and analyzed at the age of 20 weeks. HSD rats mimicked the pathophysiology of HFpEF. There were no differences in heart rate, blood pressure, left ventricular (LV) systolic function, or the extent of LV hypertrophy between HSD rats with or without vildagliptin. However, vildagliptin decreased LV end-diastolic pressure, the most reliable hemodynamic parameter of HFpEF in HSD rats. Vildagliptin also decreased the LV distensibility index, a sensitive marker of LV diastolic function in HSD rats. Vildagliptin decreased the expression of collagen genes in HSD hearts and attenuated LV interstitial fibrosis (HSD with vehicle and vildagliptin, 2.9% vs. 1.9%; P < 0.05). Furthermore, vildagliptin administration reduced both plasma renin activity and aldosterone concentrations in HSD rats. A DPP-IV inhibitor, vildagliptin, improved the severity of LV fibrosis, and thus, diastolic dysfunction of HFpEF in Dahl salt-sensitive hypertensive rats. DPP-IV inhibitors are promising medicines for treatment of HFpEF in patients with diabetes mellitus.
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http://dx.doi.org/10.1016/j.yjmcc.2019.03.009DOI Listing
April 2019

PARALLEL-HF - A Paradigm Shift for Heart Failure Treatment in Japan?

Circ J 2018 09 13;82(10):2479-2480. Epub 2018 Sep 13.

Department of Clinical Research and Development, National Cerebral and Cardiovascular Research Center.

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http://dx.doi.org/10.1253/circj.CJ-18-0939DOI Listing
September 2018

Mathematical Modeling for Scrub Typhus and Its Implications for Disease Control.

J Korean Med Sci 2018 Mar 19;33(12):e98. Epub 2018 Mar 19.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Korea.

Background: The incidence rate of scrub typhus has been increasing in the Republic of Korea. Previous studies have suggested that this trend may have resulted from the effects of climate change on the transmission dynamics among vectors and hosts, but a clear explanation of the process is still lacking. In this study, we applied mathematical models to explore the potential factors that influence the epidemiology of tsutsugamushi disease.

Methods: We developed mathematical models of ordinary differential equations including human, rodent and mite groups. Two models, including simple and complex models, were developed, and all parameters employed in the models were adopted from previous articles that represent epidemiological situations in the Republic of Korea.

Results: The simulation results showed that the force of infection at the equilibrium state under the simple model was 0.236 (per 100,000 person-months), and that in the complex model was 26.796 (per 100,000 person-months). Sensitivity analyses indicated that the most influential parameters were rodent and mite populations and contact rate between them for the simple model, and trans-ovarian transmission for the complex model. In both models, contact rate between humans and mites is more influential than morality rate of rodent and mite group.

Conclusion: The results indicate that the effect of controlling either rodents or mites could be limited, and reducing the contact rate between humans and mites is more practical and effective strategy. However, the current level of control would be insufficient relative to the growing mite population.
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http://dx.doi.org/10.3346/jkms.2018.33.e98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852423PMC
March 2018

Association between Exposure to Traffic-Related Air Pollution and Prevalence of Allergic Diseases in Children, Seoul, Korea.

Biomed Res Int 2017 13;2017:4216107. Epub 2017 Sep 13.

Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.

Although there has been suggestive evidence of the association between TRAP and ADs, findings remained inconsistent possibly due to limited population. We investigated the association between TRAP and ADs in a large population of children with rich spatial coverage and expanded age span in Seoul, Korea. TRAP exposures were estimated by categorized proximity to the nearest major road (≤150, 150-300, 300-500, and >500 m) and density of major roads within 300 meters from children's residences. We estimated the association between two TRAP exposures and three ADs using generalized mixed model after adjusting for individual characteristics. We also investigated whether the association varied by household and regional socioeconomic status. We found associations of atopic eczema with road density [OR = 1.08; 95% CI = 1.01-1.15] and road proximity [1.15, 1.01-1.32; 1.17, 1.03-1.34; and 1.16, 1.01-1.34 for ≤150, 150-300, and 300-500 m, resp., compared to >500 m]. There was no association with asthma and allergic rhinitis. Effect estimates were generally the highest in the low socioeconomic region. Children living in areas surrounded by large and busy roads were likely to be at greater risks for atopic eczema, with increased vulnerability when living in deprived areas.
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http://dx.doi.org/10.1155/2017/4216107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615949PMC
June 2018

Validating a single-question depression measure among older adults.

Int Psychogeriatr 2018 01 20;30(1):69-76. Epub 2017 Sep 20.

Department of Public Health Science,Graduate School of Public Health,Seoul National University,Seoul,Republic of Korea.

Background: A single-item depression measure may not be adequate in capturing the complex entity of mental health, despite wide use of this indicator in community studies. This study evaluated the accuracy of a single-question depression measure in comparison to two composite indices-the Center for Epidemiologic Studies Depression Scale (CESD) and the Geriatric Depression Scale (GDS).

Materials And Methods: A total of 800 elderly participants ranging from 60 to 89 years of age and residing in Seoul were recruited using a multistage sampling scheme in 2015. The survey was conducted by trained interviewers with a constructed questionnaire. Reliability and validity measures such as the Kappa index, sensitivity, specificity, PPV, NPV, and AUC were used to evaluate the accuracy of the single question measure. Socio-demographic group differences in accuracy were compared by age, sex, marital status, education, employment, and financial status.

Results: The prevalence of depression by a single-question measure was much lower than those of CESD and GDS (5.5%, 12.3%, and 12.1%, respectively). The sensitivity of the single-item measure, based on CESD and GDS, was extremely low at 30.6% and 36.1%. In the subgroup analysis, however, there was a marked educational discrepancy in all accuracy measures; in sensitivity, people with a university degree or higher showed about 2.4 times higher sensitivity than those having only a primary school education.

Conclusions: The results show that a single-question depression measure should be used with caution. In addition, the single-question measure could substantially underestimate depression among the risk group of older adults.
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http://dx.doi.org/10.1017/S1041610217001673DOI Listing
January 2018
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