Hydrolyzed Collagen Tripeptide Promotes Longitudinal Bone Growth in Childhood Rats via Increases in Insulin-Like Growth Factor-1 and Bone Morphogenetic Proteins.

Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 µg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01).

Mechanistic modelling for African swine fever transmission in the Republic of Korea.

Under the current African swine fever (ASF) epidemic situation, a science-based ASF-control strategy is required. An ASF transmission mechanistic model can be used to understand the disease transmission dynamics among susceptible epidemiological units and evaluate the effectiveness of an ASF-control strategy by simulating disease spread results with different control options. The force of infection, which is the probability that a susceptible epidemiological unit becomes infected, could be estimated by applying an ASF transmission mechanistic model. The government needs to plan an ASF-control strategy based on an ASF transmission mechanistic model.

Spatial epidemiology of highly pathogenic avian influenza subtype H5N6 in Gyeonggi Province, South Korea, 2016-2017.

Over 4 months in the winter of 2016-2017, 343 poultry farms in South Korea reported highly pathogenic avian influenza (HPAI) H5N6 occurrences, leading to the culling of 40 million poultry. Our study aimed to describe the spatial epidemiology of the 2016-2017 HPAI H5N6 outbreak in Gyeonggi Province, the most affected area in South Korea, comprising 35.9% (123) of the HPAI-infected poultry farms, to identify spatial risk factors for the increased probability of HPAI H5N6 occurrence, and to delineate areas with the highest likelihood of infection among different target poultry species. Although the poultry density was risk factor for the all species, rice paddy was only identified as risk factor for chicken and duck farms, not for other species farms suggesting that different biosecurity measures are required depending on the species. Although spatial effects of HPAI occurrence tended to be clustered within 16 km, the cluster range was reduced to 7 km when considering the identified risk factors, indicating a more geographically focused outbreak response when taking risk factors into account. The areas identified with the highest likelihood of infection can provide evidence, with accessibility to policymakers, to improve risk-based surveillance for HPAI. Our findings provide epidemiological understanding helpful in improving surveillance activity and assisting in the design of more cost-effective intervention policies related to future HPAI outbreaks in South Korea.

Estimation of Serial Interval and Reproduction Number to Quantify the Transmissibility of SARS-CoV-2 Omicron Variant in South Korea.

The omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the predominant variant in South Korea from late January 2022. In this study, we aimed to report the early estimates of the serial interval distribution and reproduction number to quantify the transmissibility of the omicron variant in South Korea between 25 November 2021 and 31 December 2021. We analyzed 427 local omicron cases and reconstructed 73 transmission pairs. We used a maximum likelihood estimation to assess serial interval distribution from transmission pair data and reproduction numbers from 74 local cases in the first local outbreak. We estimated that the mean serial interval was 3.78 (standard deviation, 0.76) days, which was significantly shorter in child infectors (3.0 days) compared to adult infectors (5.0 days) (p < 0.01). We estimated the mean reproduction number was 1.72 (95% CrI, 1.60−1.85) for the omicron variant during the first local outbreak. Strict adherence to public health measures, particularly in children, should be in place to reduce the transmission risk of the highly transmissible omicron variant in the community.

Serial Interval and Transmission Dynamics during SARS-CoV-2 Delta Variant Predominance, South Korea.

We estimated mean serial interval and superspreading potential for the Delta variant of severe acute respiratory syndrome coronavirus 2 in South Korea. Intervals were similar for the first (3.7 days) and second (3.5 days) study periods. Risk for superspreading events was also similar; 23% and 25% of cases, respectively, seeded 80% of transmissions.

Transmission Dynamics of the Delta Variant of SARS-CoV-2 Infections in South Korea.

BACKGROUND: The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the predominant variant worldwide at the time of this study. However, its transmission dynamics were unclear. METHODS: We analyzed 405 local cases infected with the Delta variant of SARS-CoV-2 and temporal patterns of viral shedding identified between 22 June and 31 July 2021 in Daejeon, South Korea. RESULTS: Overall, 20% were presymptomatic at the time of epidemiological investigation. We identified 6 clustered outbreaks, and all were associated with indoor facilities. In 23 household contacts, the secondary attack rate was 63%. We estimated the mean serial interval as 3.26 days (95% credible interval, 2.92-3.60), and 15% (95% confidence interval, 13%-18%) of cases seeded 80% of all local transmission. Analysis of the nasopharyngeal swab samples identified virus shedding from the presymptomatic cases and the highest viral load was observed 2 days after symptom onset. CONCLUSIONS: Our findings suggest that the Delta variant is highly transmissible in indoor settings and households. Rapid contact tracing, isolation of the asymptomatic contacts, strict adherence to public health measures, and increased uptake of coronavirus disease 2019 (COVID-19) vaccination, including booster doses, are needed to reduce community transmission of the Delta variant.

Machine learning-driven dynamic risk prediction for highly pathogenic avian influenza at poultry farms in Republic of Korea: Daily risk estimation for individual premises.

Highly pathogenic avian influenza (HPAI) is a fatal zoonotic disease that damages the poultry industry and endangers human lives via exposure to the pathogen. A risk assessment model that precisely predicts high-risk groups and occurrence of HPAI infection is essential for effective biosecurity measures that minimize the socio-economic losses of massive outbreaks. However, the conventional risk prediction approaches have difficulty incorporating the broad range of factors associated with HPAI infections at poultry holdings. Therefore, it is difficult to accommodate the complexity of the dynamic transmission mechanisms and generate risk estimation on a real-time basis. We proposed a continuous risk prediction framework for HPAI occurrences that used machine learning algorithms (MLAs). This integrated environmental, on-farm biosecurity, meteorological, vehicle movement tracking, and HPAI wild bird surveillance data to improve accuracy and timeliness. This framework consisted of (i) the generation of 1788 predictors from six types of data and reconstructed them with an outcome variable into a data mart based on a temporal assumption (i.e. infected period and day-ahead forecasting); (ii) training of the predictors with the temporally rearranged outcome variable that corresponded to HPAI H5N6 infected state at each individual farm on daily basis during the 2016-2017 HPAI epidemic using three different MLAs [Random Forest, Gradient Boosting Machine (GBM), and eXtreme Gradient Boosting]; (iii) predicting the daily risk of HPAI infection during the 2017-2018 HPAI epidemic using the pre-trained MLA models for each farm across the country. The models predicted the high risk to 8-10 out of 19 infected premises during the infected period in advance. The GBM MLAs outperformed the 7-day forecasting of HPAI prediction at individual poultry holdings, with an area under the curve (AUC) of receiver operating characteristic of 0.88. Therefore, this approach enhances the flexibility and timing of interventions against HPAI outbreaks at poultry farms.

Corrigendum to: Temporal Changes in the Risk of Superspreading Events of Coronavirus Disease 2019.

[This corrects the article DOI: 10.1093/ofid/ofab350.].

Basic reproduction number of African swine fever in wild boars (Sus scrofa) and its spatiotemporal heterogeneity in South Korea.

BACKGROUND: African swine fever (ASF) is a hemorrhagic fever occurring in wild boars (Sus scrofa) and domestic pigs. The epidemic situation of ASF in South Korean wild boars has increased the risk of ASF in domestic pig farms. Although basic reproduction number (R0) can be applied for control policies, it is challenging to estimate the R0 for ASF in wild boars due to surveillance bias, lack of wild boar population data, and the effect of ASF-positive wild boar carcass on disease dynamics. OBJECTIVES: This study was undertaken to estimate the R0 of ASF in wild boars in South Korea, and subsequently analyze the spatiotemporal heterogeneity. METHODS: We detected the local transmission clusters using the spatiotemporal clustering algorithm, which was modified to incorporate the effect of ASF-positive wild boar carcass. With the assumption of exponential growth, R0 was estimated for each cluster. The temporal change of the estimates and its association with the habitat suitability of wild boar were analyzed. RESULTS: Totally, 22 local transmission clusters were detected, showing seasonal patterns occurring in winter and spring. Mean value of R0 of each cluster was 1.54. The estimates showed a temporal increasing trend and positive association with habitat suitability of wild boar. CONCLUSIONS: The disease dynamics among wild boars seems to have worsened over time. Thus, in areas with a high elevation and suitable for wild boars, practical methods need to be contrived to ratify the control policies for wild boars.

Temporal Changes in the Risk of Superspreading Events of Coronavirus Disease 2019.

To identify the temporal change in the possible risk of superspreading events, we estimated the overdispersion parameter in 2 different periods of the coronavirus disease 2019 pandemic. We determined that the possible risk of superspreading events was reduced 90% during the second epidemic period in South Korea.

Anti-Inflammatory Effects of Heat-Processed Artemisia capillaris Thunberg by Regulating IκBα/NF-κB Complex and 15-PGDH in Mouse Macrophage Cells.

Growing evidence suggests that dietary nutrients in herbs and plants are beneficial in improving inflammatory disorders. Artemisia capillaris Thunberg (AC) is a traditional herbal medicine widely used in East Asia to treat pain, hepatotoxicity, and inflammatory disorders. Heat processing is a unique pharmaceutical method used in traditional herbal medicine to enhance the pharmacological effects and safety of medicinal plants. This study demonstrates the anti-inflammatory effects of heat-processed AC (HPAC) in lipopolysaccharide- (LPS-) treated mouse macrophage cells. HPAC reduced LPS-induced inflammatory mediators such as IL-6, IL-1ß, TNF-α, NO, and PGE2 in RAW 264.7 cells. Interestingly, 15-PGDH appears to play a pivotal role rather than COX-2 and mPGES-1 when HPAC regulated PGE2 levels. Meanwhile, HPAC showed anti-inflammatory effects by blocking IκBα phosphorylation and NF-κB nuclear translocalization. Also, we found that HO-1 upregulation was mediated by the mitogen-activated protein kinase (MAPK) pathways in HPAC-treated RAW 264.7 cells. And, in RAW 264.7 cells challenged with LPS, HPAC restored HO-1 expression, leading to NF-κB inhibition. Through further experiments using specific MAPK inhibitors, we found that, in response to LPS, the phosphorylated IκBα and activated NF-κB were attenuated by p38 MAPK/HO-1 pathway. Therefore, HPAC targeting both the IκBα/NF-κB complex and 15-PGDH may be considered as a potential novel anti-inflammatory agent derived from a natural source.

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

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.

Modelling the Spatial Distribution of ASF-Positive Wild Boar Carcasses in South Korea Using 2019-2020 National Surveillance Data.

In September 2019, African swine fever (ASF) was reported in South Korea for the first time. Since then, more than 651 ASF cases in wild boars and 14 farm outbreaks have been notified in the country. Despite the efforts to eradicate ASF among wild boar populations, the number of reported ASF-positive wild boar carcasses have increased recently. The purpose of this study was to characterize the spatial distribution of ASF-positive wild boar carcasses to identify the risk factors associated with the presence and number of ASF-positive wild boar carcasses in the affected areas. Because surveillance efforts have substantially increased in early 2020, we divided the study into two periods (2 October 2019 to 19 January 2020, and 19 January to 28 April 2020) based on the number of reported cases and aggregated the number of reported ASF-positive carcasses into a regular grid of hexagons of 3-km diameter. To account for imperfect detection of positive carcasses, we adjusted spatial zero-inflated Poisson regression models to the number of ASF-positive wild boar carcasses per hexagon. During the first study period, proximity to North Korea was identified as the major risk factor for the presence of African swine fever virus. In addition, there were more positive carcasses reported in affected hexagons with high habitat suitability for wild boars, low heat load index (HLI), and high human density. During the second study period, proximity to an ASF-positive carcass reported during the first period was the only significant risk factor for the presence of ASF-positive carcasses. Additionally, low HLI and elevation were associated with an increased number of ASF-positive carcasses reported in the affected hexagons. Although the proportion of ASF-affected hexagons increased from 0.06 (95% credible interval (CrI): 0.05-0.07) to 0.09 (95% CrI: 0.08-0.10), the probability of reporting at least one positive carcass in ASF-affected hexagons increased from 0.49 (95% CrI: 0.41-0.57) to 0.73 (95% CrI: 0.66-0.81) between the two study periods. These results can be used to further advance risk-based surveillance strategies in the Republic of Korea.

Epidemiological Characteristics of Foot-and-Mouth Disease in the Republic of Korea, 2014-2019.

This study describes the epidemiological characteristics of six epidemics of foot-and-mouth disease (FMD) in the Republic of Korea between 2014 and 2019. A total of 223 outbreaks had been confirmed in 40 municipalities across nine provinces. Most farms with FMD (194, 87%) were located in three densely populated livestock areas (Chungcheongnam-do, Gyeonggi-do, and Chungcheongbuk-do). More cases of FMD were found in farms with more than 1,000 pigs or 50 cattle (risk ratios = 1.27 for pigs; 9.46 for Korean native cattle) and fattening pigs. In farms affected by FMD, the proportion of animals with vaccine antibodies was low (5%-50% for Korean native beef cattle farms with FMD in 2017 vs. 97.5% in the surveillance in 2016). Effective control of FMD can be achieved through strict biosecurity measures, proper vaccination, regionalized management, and instilling awareness of FMD prevention in farmers.

Interpretation of the Basic and Effective Reproduction Number.

In epidemiology, the basic reproduction number (R0) is a term that describes the expected number of infections generated by 1 case in a susceptible population. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, R0 was frequently referenced by the public health community and the wider public. However, this metric is often misused or misinterpreted. Moreover, the complexity of the process of estimating R0 has caused difficulties for a substantial number of researchers. In this article, in order to increase the accessibility of this concept, we address several misconceptions related to the threshold characteristics of R0 and the effective reproduction number (Rt). Moreover, the appropriate interpretation of the metrics is discussed. R0 should be considered as a population-averaged value that pools the contact structure according to a stochastic transmission process. Furthermore, it is necessary to understand the unavoidable time lag for Rt due to the incubation period of the disease.

Multilocus genotyping of Giardia duodenalis from pigs in Korea.

Giardia duodenalis (syn. G. intestinalis, G. lamblia) is an important zoonotic parasite infecting livestock (including pigs) through ingesting cysts in contaminated food or water. This parasite has been classified into eight different genetic assemblages, A to H. Here, we examined the individual-level prevalence of G. duodenalis in domestic pig farms and confirmed host specificity by genotype comparisons. Samples were collected from southern and central Korea, between May 2017 and January 2019. DNA directly extracted from 745 pig fecal specimens were tested by PCR for G. duodenalis small subunit ribosomal RNA (ssu rRNA), glutamate dehydrogenase (gdh), and ß-giardin gene sequences. Based on ssu rRNA PCR, 110 (14.8%) were positive for G. duodenalis. Infection risk was the highest in the fattener group (31/139, 22.3%) and during the autumn season (52/245, 21.2%: p < .001). No statistically significant differences in risk for infection were observed between fecal types (normal versus diarrheal). Fifty ssu rRNA samples, three gdh samples, and five ß-giardin samples were successfully sequenced and genotyped. Ssu rRNA assemblage sequence analysis identified E (40.0%, 20/50), D (34.0%, 17/50), C (24.0%, 12/50), and A (2.0%, 1/50). The gdh locus identified three samples as assemblage E, and the ß-giardin locus identified four samples as assemblage E and one as assemblage C. Assemblage A sequences obtained (ssu rRNA; MK430919) had 100% identity with Giardia sequences isolated from a Korean individual (AJ293301), indicating the potential of zoonotic transmission. Continuous management and monitoring for prevention of transmission and protection of animal and human health are essential.

Estimation of the Excess COVID-19 Cases in Seoul, South Korea by the Students Arriving from China.

Background: In March 2020, overall, 37,000 international students from China, a country at risk of the 2019-novel coronavirus (COVID-19) infection has arrived in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in the Korean home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students from China, we used a deterministic compartmental model for epidemic and performed a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the number of the infected individuals would reach 40-72 from 12 March-24 March with the arrival of 0.2% of pre-infectious individuals. Furthermore, the number of isolated individuals would peak at 40-64 from 13 March-27 March in Seoul, South Korea. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics by the international student from China were less likely to occur in Seoul, South Korea. Conclusions: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine of the individuals from countries with the virus risk are warranted along with other containment policies.

Augmented Mechanical Forces of the Surface-Modified Nanoporous Acupuncture Needles Elicit Enhanced Analgesic Effects.

Over the past several decades, clinical studies have shown significant analgesic effects of acupuncture. The efficacy of acupuncture treatment has improved with the recent development of nanoporous needles (PN), which are produced by modifying the needle surface using nanotechnology. Herein, we showed that PN at acupoint ST36 produces prolonged analgesic effects in an inflammatory pain model; the analgesic effects of PN acupuncture were sustained over 2 h, while those using a conventional needle (CN) lasted only 30 min. In addition, the PN showed greater therapeutic effects than CN after 10 acupuncture treatments once per day for 10 days. We explored how the porous surface of the PN contributes to changes in local tissue, which may in turn result in enhanced analgesic effects. We showed that the PN has greater rotational torque and pulling force than the CN, particularly at acupoints ST36 and LI11, situated on thick muscle layers. Additionally, in ex vivo experiments, the PN showed greater winding of subcutaneous connective tissues and muscle layers. Our results suggest that local mechanical forces are augmented by the PN and its nanoporous surface, contributing to the enhanced and prolonged analgesic effects of PN acupuncture.

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

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.

Low risk of avian influenza A (H5N6) transmission to depopulation workers in Korea.

An outbreak of highly pathogenic avian influenza A (H5N6) virus occurred between November 20, 2016, and March 1, 2017 in poultry farms, in the Gyeonggi Province, Republic of Korea. To identify the risk of transmission of H5N6 to depopulation workers, active and passive surveillance was conducted. Virological testing of respiratory swabs with real-time reverse transcription-polymerase chain reaction was performed for workers who reported respiratory symptoms. Among 4633 depopulation workers, 22 reported respiratory symptoms, but all tested negative for H5N6. Personal protective equipment in addition to antiviral prophylaxis was adequate to limit transmission of H5N6 from poultry to humans.