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Since October 2020, H5N1 clade 2.3.4.4b high pathogenicity avian influenza (HPAI) viruses have spread to many countries. Although these viruses evolved from Eurasian ancestors, reassortant with other LPAI viruses has generated various genotypes. Here, we identified three H5N1 HPAI viruses belonging to clade 2.3.4.4b; these viruses were isolated from mandarin duck, common teal, and domestic breeder ducks in October 2022 during an avian influenza (AI) active surveillance program. Two of the H5N1 viruses (MD/WA496 and BD/H493) have been found sporadically in China, Russia, and Korea. It is presumed that two viruses with a similar gene constellation isolated in Russia, China, and Korea were introduced into the breeding area during the spring migration, and were introduced newly to Korea during the autumn migration. Due to international bird migration, the other virus (CT/WA537) is most similar (99.3–99.8%) to a virus detected in North Dakota, USA in April 2022. These results suggest that H5N1 viruses with at least two genotypes were introduced at the same time into Korea during the autumn of 2022, and that they originated from Eurasian breeding grounds and North America. Thus, multiple 2.3.4.4b H5N1 viruses were introduced into Korea during the autumn season of 2022.

Background Acinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children. Methods Acinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001–2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed. Results In total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1–7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P baumannii Acinetobacter spp. (2.1%). During 2014–2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period. Conclusion Complete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

Background In women with autoimmune rheumatic disorders (ARD), pregnancy complications or postpartum events are more frequent compared to the general population. Transplacental autoantibodies or cytokines influence various fetal and neonatal outcomes. We compared the growth patterns of babies born to mothers with ARD versus healthy mothers to assess the long-term growth outcomes of children born to women with ARD. Methods This was a retrospective age-matched cohort analyses of babies born to mothers with ARD from the hospitals belonging to the Catholic University of Korea between 2010 and 2017. Demographic and autoimmune laboratory test data of the mothers and newborns were assessed. Neonatal growth was measured in terms of height and weight, measured at birth and follow-up examinations. Results We enrolled 142 infants from mothers with ARD and 149 infants from healthy mothers. There was no significant difference between mothers with ARD and healthy mothers in terms of delivery age, parity, abortion, and premature delivery history. The mothers with ARD were diagnosed with systemic lupus erythematosus (81%), Sjogren syndrome (6%), and other autoimmune phenomena (11%). The groups were significantly different in terms of neonatal characteristics such as prematurity, gestational age, birth weight, and height, but not in Apgar score and delivery type. For most neonates, autoimmune laboratory results were normalized within 1 year, except for anti-La/SSB antibody, which remained high in some. The height and weight for age z-score were lower than the normal age groups at birth but showed catch-up growth by 2 years of age. Conclusions Low birthweight and prematurity at birth for neonates born to mothers with ARD could be caught up by 2 years of age, and maternal ARD does not affect the growth of their offspring.

Purpose: Although many genomic alterations have been observed in lung cancer, their clinicopathologic significance has not been thoroughly investigated. This study screened the genomic aberrations across the whole genome of non–small cell lung cancer cells with high-resolution and investigated their clinicopathologic implications.Experimental Design: One-megabase resolution array comparative genomic hybridization was applied to 29 squamous cell carcinomas and 21 adenocarcinomas of the lung. Tumor and normal tissues were microdissected and the extracted DNA was used directly for hybridization without genomic amplification. The recurrent genomic alterations were analyzed for their association with the clinicopathologic features of lung cancer.Results: Overall, 36 amplicons, 3 homozygous deletions, and 17 minimally altered regions common to many lung cancers were identified. Among them, genomic changes on 13q21, 1p32, Xq, and Yp were found to be significantly associated with clinical features such as age, stage, and disease recurrence. Kaplan-Meier survival analysis revealed that genomic changes on 10p, 16q, 9p, 13q, 6p21, and 19q13 were associated with poor survival. Multivariate analysis showed that alterations on 6p21, 7p, 9q, and 9p remained as independent predictors of poor outcome. In addition, significant correlations were observed for three pairs of minimally altered regions (19q13 and 6p21, 19p13 and 19q13, and 8p12 and 8q11), which indicated their possible collaborative roles.Conclusions: These results show that our approach is robust for high-resolution mapping of genomic alterations. The novel genomic alterations identified in this study, along with their clinicopathologic implications, would be useful to elucidate the molecular mechanisms of lung cancer and to identify reliable biomarkers for clinical application.

Supplementary Tables S1-S4 from Genome-Wide Screening of Genomic Alterations and Their Clinicopathologic Implications in Non–Small Cell Lung Cancers

Supplemental Digital Content is available in the text., Background: Invasive bacterial infection (IBI) remains a major burden of mortality and morbidity in children. As coronavirus disease 2019 (COVID-19) emerged, stringent nonpharmaceutical interventions (NPIs) were applied worldwide. This study aimed to evaluate the impact of NPIs on pediatric IBI in Korea. Methods: From January 2018 to December 2020, surveillance for pediatric IBIs caused by 9 pathogens (S. pneumoniae, H. influenzae, N. meningitidis, S. agalactiae, S. pyogenes, S. aureus, Salmonella species, L. monocytogenes and E. coli) was performed at 22 hospitals throughout Korea. Annual incidence rates were compared before and after the COVID-19 pandemic. Results: A total of 651 cases were identified and the annual incidence was 194.0 cases per 100,000 in-patients in 2018, 170.0 in 2019 and 172.4 in 2020. Most common pathogen by age group was S. agalactiae in infants < 3 months (n = 129, 46.7%), S. aureus in 3 to < 24 months (n = 35, 37.2%), Salmonella spp. in 24 to < 60 months (n = 24, 34.8%) and S. aureus in children ≥ 5 years (n = 128, 60.7%). Compared with 2018 to 2019, the incidence rate in 2020 decreased by 57% for invasive pneumococcal disease (26.6 vs. 11.5 per 100,000 in-patients, P = 0.014) and 59% for Salmonella spp. infection (22.8 vs. 9.4 per 100,000 in-patients, P = 0.018). In contrast, no significant changes were observed in invasive infections due to S. aureus, S. agalactiae and E. coli. Conclusions: The NPIs implemented during the COVID-19 pandemic reduced invasive diseases caused by S. pneumoniae and Salmonella spp. but not S. aureus, S. agalactiae and E. coli in children.

The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future.

Since June 2020, a new H9N2 virus of the Y280 lineage has been epidemic in Korea. Initially, a Korean commercial vaccine against the Y280 and Y439 lineages of H9N2 was evaluated for use in SPF chickens. A single vaccination did not protect chickens against virus of the Y280 lineage, with no significant reduction in virus shedding and a 37.5% inhibition in virus recovery rate in cecal tonsil. rgHS314 was selected as a vaccine candidate, showing immunogenicity in SPF chickens, and was highly productive in eggs. Moreover, rgHS314 protected with high levels of protective immunity and significantly reduced virus shedding, with 100% and 83.3% inhibition of virus recovery in the cecal tonsil against homologous and heterologous challenge viruses, respectively. Taken together, these data suggest that a single vaccination with this recombinant vaccine candidate could elicit cross-reactive immune responses capable of protecting chickens against H9N2 viruses of the Y439 and Y280 lineages.

Background Nasopharyngeal (NP) colonization with Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) is common in children, and may evolve as the source of invasive infections. In Korea, the pneumococcal conjugate vaccines (PCVs) were introduced >10 years ago, enabling the authors to study the effect of the vaccine in preventing carriage. Methods NP swabs were taken and a household survey was conducted at daycare centres located in different regions of Korea in 2014 and 2019. Pneumococcal serotypes were identified using the Quellung method and sequencing. NTHi were identified based on pilA and bexA genes. Results In total, 1460 NP swabs were obtained with pneumococcal carriage rates of 36.4–42.1% and NTHi carriage rates of 36.5–26.7%. Among children carrying pneumococci, a significant increase was seen in serotype 23A between 2014 and 2019 (from 12.6% to 22.0%; P=0.005). Children who had received PCV were at lower risk of vaccine-type carriage (2.9% vs 0.8%; P=0.005). Conclusions Between 2014 and 2019, the proportion of children carrying serotype 23A increased significantly, while the carriage rate of NTHi decreased. Continuous surveillance is needed to assess the long-term effects of the PCVs on carriage dynamics of pneumococcus and NTHi.

The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis (NEC)/Feeding intolerance (FI) compared to those that did not develop NEC/FI. During the study period, a total of 108 preterm and term newborns' first passed meconium occurring within 72 hours of birth were collected and microbiome analyzed. Meconium microbiomes showed a disruption in the percentages of the core microbiome constituents in both the phylum and genus levels in infants born < 30 weeks of gestational age (GA) compared to those born ≥ 30 weeks of GA. In the phylum level, Bacteroidetes and Firmicutes, and in the genus level, Prevotella and Bacteroides, were predominant, with Prevotella accounting for 20–30% of the relative abundance. As GA increased, a significant increase in the relative abundance of Bacteroidetes (P for trend < 0.001) and decrease in Proteobacteria (P for trend = 0.049) was observed in the phylum level. In the genus level, as GA increased, Prevotella (P for trend < 0.001) and Bacteroides (P for trend = 0.002) increased significantly, whereas Enterococcus (P for trend = 0.020) decreased. Compared to the control group, the meconium of infants that later developed NEC/FI had significantly lower alpha diversities but similar beta-diversities. Furthermore, the NEC/FI group showed a significantly lower abundance of Bacteroidetes (P < 0.001), and higher abundance of Firmicutes (P = 0.034). To conclude, differences were observed in the composition of the first passed meconium in preterm and term infants that later develop NEC/FI compared to those that did not.

Infectious diarrhea is a global pediatric health concern; therefore, rapid and accurate detection of enteropathogens is vital. We evaluated the BioFire® FilmArray® Gastrointestinal (GI) Panel with that of comparator laboratory tests. Stool samples of pediatric patients with diarrhea were prospectively collected and tested. As a comparator method for bacteria, culture, conventional PCR for diarrheagenic E. coli, and Allplex GI-Bacteria(I) Assay were tested. For discrepancy analysis, BD MAX Enteric Bacterial Panel was used. As a comparator method for virus, BD MAX Enteric Virus Panel and immunochromatography was used and Allplex GI-Virus Assay was used for discrepancy analysis. The “true positive” was defined as culture-positive and/or positive results from more than two molecular tests. Of the 184 stool samples tested, 93 (50.5%) were true positive for 128 pathogens, and 31 (16.9%) were positive for multiple pathogens. The BioFire GI Panel detected 123 pathogens in 90 of samples. The BioFire GI Panel demonstrated a sensitivity of 100% for 12 targets and a specificity of >95% for 16 targets. The overall positive rate and multiple pathogen rate among patients in the group without underlying diseases were significantly higher than those in the group with hematologic disease (57.0% vs. 28.6% (p = 0.001) and 20.4% vs. 4.8% (p = 0.02), respectively). The BioFire GI Panel provides comprehensive results within 2 h and may be useful for the rapid identification of enteropathogens.

Background Mycoplasma pneumoniae (MP) is one of the most common causes of bacterial pneumonia in children. In the recent decade, macrolide-resistant MP (MRMP) has been increasing in proportion, leading to children unresponsive to initial macrolide therapy. The purpose of this study was to evaluate the outcomes of children with lobar or segmental MP pneumonia unresponsive to initial macrolide therapy, who received non-macrolide (NM), macrolide plus steroids (M+S), and non-macrolide plus steroids (NM+S) according to the 2019 guideline during the 2019-2020 Mycoplasma epidemic in South Korea. Methods This was a retrospective cohort study of children below 18 years old, admitted during the 2019-2020 MP outbreak for lobar or segmental MP pneumonia. The inclusion criteria were as follows: 1) sputum or nasopharyngeal swab MP PCR positive, 2) no history of pneumonia within one month of positive MP PCR, 3) lobar or segmental pneumonia on chest x-ray, and 4) initial treatment with macrolide monotherapy. Children that were unresponsive to the initial 3-5-day macrolide monotherapy were divided into 3 groups depending on the next regimen: NM, M+S, and NM+S group. Their outcomes were assessed. Results During May 2019 to March 2020 MP epidemic, a total 190 patients that fit all of the inclusion criteria were included as study participants. Of these, 16.8% (n=32/190) were responsive to initial macrolide monotherapy and 83.2% (158/190) were unresponsive. Of the 158 patients unresponsive during the initial 5-day macrolide therapy, 8.2% (n=13) were switched to a NM, 75.9% (n=120) were added steroids (M+S), and 15.8% (25/158) were switched to a non-macrolide plus steroids (NM+S). Treatment success rates were 46%, 81%, and 100% in the NM, M+S, and NM+S groups, respectively (P=0.001). Compared to patients in the NM+S group, those in the M+S group were 8.0 (Confidence interval [CI], 1.3-61.7; P=0.046) times more likely to have prolonged fever ≥4 days after the switch in treatment regimen compared to patients with NM+S, and 10.7 (CI, 1.5-108.7; P=0.046) times more likely in the NM group. Conclusion In patients with severe mycoplasma pneumonia with failure of response to initial macrolide therapy, a non-macrolide antibiotic plus steroid combination had the highest treatment success rate and shorter duration of fever. Disclosures All Authors: No reported disclosures.

Background Streptococci are the dominant species in the human oral cavity and upper respiratory tract. Oral mucositis affects 30–40% of the patients receiving chemotherapy and 80% undergoing HSCT. During episode of oral mucositis, patients are at a risk for invasive infections caused by opportunistic pathogens in the oral cavity. The purpose of this study was to investigate the clinical characteristics of S. mitis/oralis invasive infection, and find patients at high risk for with S. mitis/oralis infection in order to prevention of S. mitis/oralis bacteremia. Methods Patients receiving chemotherapy or stem cell transplant for malignancies and primary immunodeficiencies at the pediatric bone marrow transplant center of Seoul St. Mary's hospital admitted during January 2017 to December 2020 for blood stream infections were included in this study. Chart review of the patients were done retrospectively. Results During the four year study period, there were 4,647 admissions, and 2,358 (50.7%) experienced at least 1 episode of fever. Overall, the incidence of bacteremia was 10.9% of all febrile children. The most common pathogen causing bacteremia was S. mitis/oralis (24%), followed by E. coli (14.3%), Klebsiella spp. (10.5%), and S. epidermidis (7.4%). Candida sepsis occurred in 3.5% of the children. By year, the proportion of bacteremia caused by S. mitis/oralis was 19% in 2017, 21% in 2018, 41% in 2019, and 25% in 2020. 51% of S. mitis/oralis bacteremia occurred 8-14 days after day 0 of chemotherapy. A multivariate analyses on risk factors for S. mitis/oralis bacteremia was the underlying disease AML (OR, 4.6; 95% CI, 2.4-8.7; P< 0.001), and the use of cytarabine (OR, 4.5; 95% CI, 2.4-8.5; P< 0.001). Compared to ALL, AML has a HR 3.7 (95% CI 1.9-7.2) of bacteremia with S. mitis/oralis. Prolonged duration of fever ( >7 days) was observed in 13.4% of the patients, and a fever duration >14 days was observed in 2 patients. Complications such as septic shock, n=4 (6.0%), ARDS, n=1 (1.5%), infective endocarditis, n=2 (3.0%) were observed. Conclusion S. mitis/oralis sepsis causes significant morbidity in patients undergoing treatment for malignancies. Patients with AML are at the highest risk, especially after induction or consolidation chemotherapy including cytarabine. Disclosures All Authors: No reported disclosures.

Background Sepsis is a complication frequently encountered in children with underlying malignancies, especially due to a majority of patients having indwelling venous catheters. Indications for catheter removal among children with central-line associated blood stream infection (CLABSI) should follow the recommendations for adults, however, difficulties in vascular access often leads to attempting treatment without catheter removal. Therefore, the primary aim of this study was to find risk factors for recurrent sepsis in children undergoing chemotherapy of HSCT and examine whether more aggressive catheter removal after CLABSI in children is necessary. Methods In the Pediatric Bone Marrow Transplant Center of Seoul St. Mary’s Hospital, positive blood cultures were prospectively monitored to control and prevent outbreaks. The date of culture, culture results, symptoms presented, category of blood stream infections (by the CDC/NHSN surveillance definition (2021) of Bloodstream infections), and central-line associated blood stream infection (CLABSI) events were monitored. Results During September 2016 to February 2021, a total 280 cases of laboratory confirmed bloodstream infections (LCBI) or Mucosal Barrier Injury LCBI (MBI-LCBI) were diagnosed in children < 18 years old with underlying malignancies. Of these, 52.9% (n=148) were male, and the mean age was 9.7 (SD±6.1) years old. CLABSI was diagnosed in 51.8% (n=145), and the most common pathogens cultured were S. mitis/oralis (24.0%, n=67), E. coli (15.4%, n=43), and coagulase negative Staphylococci (CNS) (10.4%, n=29). Recurrent sepsis occured in 17.1% (n=48), and 9.6% (n=27) had two indwelling catheters . Multivariable analysis showed that factors associated with recurrent blood stream infections were as follows: duration of indwelling catheter (OR, 1.002; 95% CI, 1.001-1.004; P< 0.001) and no removal of central lines after previous episode (OR, 51.143; 95% CI, 6.6-395.0; P< 0.001). Conclusion Permanent central lines should be removed as soon as possible, and more aggressive approach in permanent catheter removal after LCBSIs in children is necessary to reduce recurrent infections. Disclosures All Authors: No reported disclosures.

Invasive bacterial infection (IBI) causes a significant burden in infants. In this study, we analyzed changes in epidemiology of IBI among infants in Korea.A retrospective multicenter-based surveillance for IBIs in infants3 months of age was performed during 2006-2020. Cases were classified as an early-onset disease (EOD) (0-6 days) or late-onset disease (LOD) (7-89 days). The temporal trend change in proportion of pathogens was analyzed.Among 1545 cases, the median age was 28 days (IQR: 12, 53) and EOD accounted for 17.7%. Among pathogens, S. agalactiae (40.4%), E. coli (38.5%), and S. aureus (17.8%) were the most common and attributed for 96.7%. Among EOD (n = 274), S. agalactiae (45.6%), S. aureus (31.4%), E. coli (17.2%) and L. monocytogenes (2.9%) were most common. Among LOD (n = 1274), E. coli (43.1%), S. agalactiae (39.3%), S. aureus (14.9%) and S. pneumoniae (1.3%) were most common. In the trend analysis, the proportion of S. aureus (r s = -0.850, P0.01) decreased significantly, while that of S. agalactiae increased (r s = 0.781, P0.01).During 2006-2020, among IBI in infants3 months of age, S. agalactiae, E. coli, and S. aureus were most common and an increasing trend of S. agalactiae was observed.

In the last few decades, macrolide-resistant Mycoplasma pneumoniae (MRMP) has been increasing in proportion. This study aimed to evaluate the treatment outcomes of children with lobar or segmental MP pneumonia unresponsive to the initial 3–5-day macrolide therapy, who then switched to either a non-macrolide, macrolide + steroid, or a non-macrolide + steroid regimen, according to the 2019 KSPID and KAPARD guideline during the 2019–2020 Mycoplasma epidemic in South Korea. A total of 190 patients

In the last few decades, macrolide-resistant

Background Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy. Results As evidenced by protein chip analysis, FBXL17 inversely correlated with SPAST-M1 at the protein level in vitro and, also in vivo during embryonic developmental stage. SPAST-M1 protein interacted with FBXL17 specifically via the BTB domain at the N-terminus of SPAST-M1. The SCFFBXL17 E3 ubiquitin ligase complex degraded SPAST-M1 protein in the nuclear fraction in a proteasome-dependent manner. SPAST phosphorylation occurred only in the cytoplasmic fraction by CK2 and was involved in poly-ubiquitination. Inhibition of SCFFBXL17 E3 ubiquitin ligase by small chemical and FBXL17 shRNA decreased proteasome-dependent degradation of SPAST-M1 and induced axonal extension. The SPAST Y52C mutant, harboring abnormality in BTB domain could not interact with FBXL17, thereby escaping protein regulation by the SCFFBXL17 E3 ubiquitin ligase complex, resulting in loss of functionality with aberrant quantity. Although this mutant showed shortening of axonal outgrowth, low rate proliferation, and poor differentiation capacity in a 3D model, this phenotype was rescued by inhibiting SCFFBXL17 E3 ubiquitin ligase. Conclusions We discovered that a novel pathway, FBXL17-SPAST was involved in pathogenicity of HSP by the loss of function and the quantitative regulation. This result suggested that targeting FBXL17 could provide new insight into HSP therapeutics.

This article presents the “Christology of Water” from Feng Shui cosmology, which promotes liberating women and nature from the oppression perpetrated against them by contemporary Korean churches, which have sexism and eco-antipathy at their heart. The presentation of the “Christology of Water” from Feng Shui envisions a new eco-feminist theological solution to the critique of patriarchies and anthropocentricism alienating and suppressing women and nature. This “Christology of Water” developed from the metaphorical languages of Feng Shui suggests a contextual hermeneutic through reinterpretation from the eco-feminist perspective.

The skin exhibits tremendous regenerative potential, as different types of progenitor and stem cells regulate skin homeostasis and damage. However, in vitro primary keratinocytes present with several drawbacks, such as high donor variability, short lifespan, and limited donor tissue availability. Therefore, more stable primary keratinocytes are needed to generate multiple uniform in vitro and in vivo skin models.We identified epidermal progenitor cells from primary keratinocytes using Integrin beta 1 (ITGB1) an epidermal stem cell marker markedly decreased after senescence in vitro. Epidermal progenitor cells exhibited unlimited proliferation and the potential for multipotent differentiation capacity. Moreover, they could completely differentiate to form an organotypic skin model including conversed mesenchymal cells in the dermis and could mimic the morphologic and biochemical processes of human epidermis. We also discovered that proliferation and the multipotent differentiation capacity of these cells relied on ITGB1 expression. Eventually, we examined the in vitro and in vivo wound healing capacity of these epidermal progenitor cells.Overall, the findings suggest that these stable and reproducible cells can differentiate into multiple lineages, including human skin models. They are a potentially powerful tool for studying skin regeneration, skin diseases, and are an alternative for in vivo experiments.

High pathogenicity H5N1 avian influenza viruses pose a threat to both animal and human health worldwide. In late 2020, outbreaks of H5 high pathogenicity avian influenza viruses belonging to clade 2.3.4.4b emerged in Europe, following on from outbreaks in East Asia in earlier years. However, very recent studies show that clade 2.3.4.4b H5N1, rather than 2.3.4.4b H5N8, has become predominant in wild birds and has infected poultry in several countries. In this study, we describe isolation of a novel H5N1 virus from a captured mandarin duck in South Korea, and another H5N1 virus from a quail farm. We performed genetic analysis of these two viruses to identify their origin and to determine their relationship with the clade 2.3.4.4b H5N1 viruses currently circulating in Europe. Based on our results, it is presumed that the novel H5N1 virus isolated in Korea originated from an unknown reassortant between clade 2.3.4.4b H5N8 viruses circulating from 2020 and other Eurasian viruses, with additional reassortment of genes and point mutations that discriminate them from the recently reported H5N1 virus in Europe.

Antithymocyte globulin (ATG) and anti-T lymphocyte globulin (ATLG) have been widely used to prevent graft-versus-host disease (GvHD), each with distinct properties and noninterchangeable doses. However, the optimal dose of ATG in children undergoing allo-PBSCT for leukemia has not yet been established. Therefore, the impact of ATG dose on overall survival (OS), relapse, GvHD, and infectious complications was investigated. Patients administered high dose (unrelated: 7.5 mg/kg, haploidentical: 10.0 mg/kg) and low dose (unrelated: 3.75 mg/kg, haploidentical: 5.0 mg/kg) ATG during two consecutive time periods were compared. There were 78 (39.8%) patients in the low dose group and 118 (60.2%) in the high dose group. OS was superior in the low dose group compared to the high dose group (P = 0.017), and relapse incidence was significantly lower in the low dose group (P = 0.022). Cumulative incidences of acute and chronic GvHD were similar between the groups (P = 0.095 and P = 0.672, respectively). Cytomegalovirus reactivation (70.3% vs. 51.3%, P = 0.007), Epstein-Barr virus reactivation (81.4% vs. 39.7%, P < 0.001), and invasive bacterial infections (12.7% vs. 0%, P = 0.001) post transplant were more frequent in the high dose group compared to the low dose group. Therefore, low dose ATG is more optimal in pediatric allo-PBSCT providing better OS while lowering the risk of relapse and infectious complications.

Background: Understanding the epidemiology and prevalence of febrile urinary tract infection (fUTI) in children is important for risk stratification and selecting appropriate urine sample collection candidates to aid in its diagnosis and treatment.Purpose: This study aimed to analyze the epidemiology, etiology, and changes in antibiotic susceptibility patterns of the first fUTI in children.Methods: This retrospective observational cohort study included children younger than 19 years of age who were diagnosed and treated for their first fUTI in 2006–2016. Electronic medical records were analyzed and radiologic images were evaluated.Results: A total of 359 patients (median age, 5.1 months; interquartile range, 3.0–10.5 months) fit the inclusion criteria; of them, 78.0% (n=280) were younger than 12 months old. The male to female ratio was 5.3:1 for patients aged 0–2 months, 2.1:1 for those 3–5 months, and 1.6:1 for those 6–11 months. Beyond 12 months of age, there was a female predominance. Escherichia coli was the leading cause (83.8%), followed by Enterococcus species (6.7%), and Klebsiella pneumoniae (3.6%). Significant yearly increases in the proportions of multidrug-resistant strains (PPP=0.03).Conclusion: fUTI was most prevalent in children younger than 12 months of age and showed a female predominance in patients older than 12 months of age. The proportion of ESBL producers causing fUTI is increasing. Carbapenems, rather than noncarbapenems, should be considered for treating fUTI caused by ESBL-producing enteric gram-negative rods to reduce short-term recurrence rates in children with VUR.

Objectives To investigate the genetic characteristics associated with eradication failure of Staphylococcus aureus in infants below 90 days old. Methods S. aureus isolated from clinical specimen cultures (blood, surgical tissue, or drainage, pus, etc.) and routine screening cultures in the neonatal intensive care unit (nasal and axillary skin swab) from patients below 90 days old were collected prospectively for 1 year, from August 2017 to July 2018. The isolates underwent typing and screening for genes associated with chlorhexidine (qacA/B), quaternary ammonium (smr), and mupirocin resistance (iles mutation, mupA, mupB), as well as Panton-Valentine leukocidin (PVL) toxin. Results During the study period, 40 nonduplicate isolates were included for analyses, of which 70.0% were methicillin-resistant S. aureus (MRSA). Mupirocin resistance was found in 25% of the total isolates; 17.4% of the colonizers; and 35.3% of the pathogens (P = 0.196). Chlorhexidine resistance gene was found in 3 MRSA isolates colonized in the nares of preterm infants. All isolates harbored the disinfectant quaternary ammonium compound (QAC) resistance gene. PVL toxin gene was found in 57.5%, and the presence of PVL gene among colonizers and pathogens was similar (69.6% vs. 41.2%, P = 0.072). Conclusions Mupirocin, chlorhexidine, and QAC-resistant MRSAs harboring the PVL toxin gene were found in the nasal carriages of preterm infants. In this highly vulnerable patient population, one-fourth of the isolates harbored mupirocin-resistant genes, and all were resistant to QAC disinfectants. These strains are associated with persistence in both carriage and environmental reservoirs within the hospitals.

The immunogenicity and protective efficacy of inactivated clade 2.3.2.1c (rgKA435) and clade 2.3.4.4c (rgES2) H5Nx vaccines, which are representatives of an avian influenza antigen bank in Korea, were examined in mice. Mice were vaccinated twice and then challenged with homologous virus. Hemagglutinin inhibition and serum neutralizing antibody titers in the rgES2-vaccinated group were higher (4.4 ± 1.7 and 10.8 ± 2.3 log2, respectively) than those in the rgKA435-vaccinated group (2.8 ± 1.1 and 2.5 ± 0.9 log2, respectively). rgES2 conferred 100% protection, with no morbidity, no severe body weight loss, and no virus replication in any of the tissues tested. By contrast, 80% of mice in the rgKA435 group survived. One mouse in this group died at 10 dpi. Virus titers in the lung and turbinate were 102.5–3.5 TCID50/0.1 ml at 3–7 dpi and 101.5 TCID50/0.1 ml at 3–5 dpi, respectively. In particular, the viral titer in the turbinate from the rgKA435 group at 3 dpi was significantly lower than that in the equivalent control group (p

Conventional concrete-filled-tube columns may have welding defects when welders of limited skill have been involved in their production; such defects could cause a rapid degradation of the columns’ strength during a fire. In the study reported in this paper, non-welded columns with mechanical strip connections were developed. Their structural performance, plus that of a typical welded column, was evaluated under both ambient and elevated temperatures. Axial loads were applied to all specimens; for fire resistance the axial load ratio was 40% and an ISO 834 standard fire curve was applied without fire protection. The non-welded columns with mechanical strip connections showed 15% higher strength under ambient temperature and resisted 40 min longer under elevated temperature compared to the typical welded column. Also, local buckling by compression was barely observed in the non-welded columns, whereas a large buckling was shown in the typical welded column under both ambient and elevated temperatures. It is concluded that non-welded columns with mechanical strip connections provide a viable way to avoid the welding problems of typical concrete-filled-tube columns, providing good performance under fire without fire protection.

The occurrence of severe outbreaks of highly pathogenic avian influenza in Korea led to establishment of a national antigen bank for emergency preparedness. Here, we developed five vaccines for this bank (clade 2.3.2.1C, clade 2.3.4.4A, B, C, and D) by reverse genetics, inactivated them with formalin, and evaluated the protective efficacy and potency of serial dilutions against lethal homologous challenge in specific-pathogen-free chickens. After vaccination with one dose, each vaccine resulted in 100% survival, with no clinical symptoms, or lack of detectable virus shedding, and high levels of pre-challenge protective immunity (8.4-10.2 log2). After vaccination with one-tenth of the full dose, protection was similar to that with the full dose. After vaccination with one-hundredth of the initial dose, survival was 20-80%, and all vaccines showed virus shedding. Four vaccines (excluding clade 2.3.2.1C) had satisfactory potency. In antibody-persistence tests, all vaccines maintained long-lasting protective immunity. Our results suggest that inactivated reverse-genetics vaccines genetically matched to outbreak viruses provide adequate protection after a single vaccination.

Changes in the epidemiology of group A streptococcus (GAS) infection is related to emm genotype. We studied the distribution of emm genotypes and their antibiotic susceptibility among Korean children.Isolates from children with GAS infection between 2012 and 2019 were collected. emm typing and cluster analysis was performed according to the Centers for Disease Control emm cluster classification. Antimicrobial susceptibility was tested using the E-test and resistance genes were analyzed for macrolide resistant phenotypes.Among 169 GAS isolates, 115 were from children with scarlet fever. Among invasive isolates, emm1 (6/22, 27.3%), emm12 (4/22, 18.2%), and emm4 (4/22, 18.2%) were most common. In scarlet fever, although emm4 (38/115, 33.0%) was the most prevalent throughout the study period, emm4 was replaced by emm3 (28/90, 31.1%) during an outbreak in 2017-2018. Among all isolates, only 2 (1.2%) exhibited erythromycin resistance and harbored both ermA and ermB genes.In this analysis of GAS isolated from Korean children, emm1 was the most prevalent in invasive infection. In scarlet fever, emm4 was prevalent throughout the study period, with an increase in emm3 during 2017-2018. GAS isolates during 2012-2019 demonstrated low erythromycin resistance.

Intussusception refers to the invagination of a part of the intestine into itself. The exact cause for this condition is unknown in most cases. The active implementation of coronavirus disease 2019 (COVID-19) infection control guidelines has reduced the spread of COVID-19 and the incidence of other infectious diseases in children. The current study aimed to identify changes in pediatric intussusception and infectious diseases after the implementation of infection control guidelines and confirm the association between intussusception and contagious diseases.We analyzed the electronic medical records of pediatric patients diagnosed with intussusception from seven hospitals in Korea between January 2017 and December 2020. We used open data from the Korea Disease Control and Prevention Agency to investigate changes in infectious diseases over the same period.Altogether, we evaluated 390 children with intussusception. There was a statistically significant decrease in the incidence of monthly visits with intussusception in the COVID-19 period group (9.0 vs. 3.5,We confirmed that implementing infection control guidelines during the COVID-19 pandemic resulted in a decrease in intussusception and viral infectious diseases. Through this result, it was possible to indirectly confirm the existing hypothesis that viral infections play a significant role in the pathophysiologic mechanism of intussusception.

Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by multiple passage of Y439 lineage viruses and then evaluated immunogenicity and protective efficacy in specific-pathogen-free chickens. We found that LBM564 could be produced at high yield in eggs (108.4EID50/0.1 mL; 1024 hemagglutinin units) and was immunogenic (8.0 ± 1.2 log2) in chickens. The vaccine showed 100% inhibition of virus in the cecal tonsil with no viral shedding detected in either oropharyngeal or cloacal swabs after challenge with homologous virus. However, it did not induce effective protection against challenge with heterologous virus. An imported commercial G1 lineage vaccine inhibited viral replication against Y280 and Y439 lineage viruses in major tissues, although viral shedding in oropharyngeal and cloacal swabs was observed up until 5 dpi after exposure to both challenge viruses. These results suggest that a single vaccination with vac564 could elicit immune responses, showing it to be capable of protecting chickens against the Y439 lineage virus. Thus, our results suggest the need to prepare suitable vaccines for use against newly emerging and re-emerging H9N2 viruses.

After primary infection, varicella zoster virus (VZV) causes prolonged latent infections that may reactivate, depending on the immunologic status of the host. We present a case of VZV reactivation in a 10-year-old male patient that underwent unrelated peripheral blood stem cell transplantation (uPBSCT) for T-lymphoblastic lymphoma with lymphoma cutis lesions. This patient had a history of herpes zoster involving the right L2-5 dermatome and trigeminal V1 dermatome prior to uPBSCT. Three months post-uPBSCT, the patient’s underlying disease relapsed, and the patient presented with lymphoma cutis lesions. A few days after a skin biopsy was performed to pathologically confirm skin relapse, vesicles appeared only involving the skin areas with lymphoma cutis. This case illustrates how decreased areas of epidermal immune mechanisms may cause atypical presentations of varicella infection.

Since 2018, Korea has been building an avian influenza (AI) national antigen bank for emergency preparedness; this antigen bank is updated every 2 years. To update the vaccine strains in the antigen bank, we used reverse genetics technology to develop two vaccine candidates against avian influenza strains belonging to clades 2.3.2.1d and 2.3.4.4h, and then evaluated their immunogenicity and protective efficacy in SPF chickens challenged with H5 viruses. The two vaccine candidates, named rgCA2/2.3.2.1d and rgES3/2.3.4.4h, were highly immunogenic, with hemagglutination inhibition (HI) titers of 8.2–9.3 log2 against the vaccine strain, and 7.1–7.3 log2 against the lethal challenge viruses (in which the HA genes shared 97% and 95.4% homology with that of rgCA2/2.3.2.1d and rgES3/2.3.4.4h, respectively). A full dose of each vaccine candidate provided 100% protection against the challenge viruses, with a reduction in clinical symptoms and virus shedding. A 1/10 dose provided similar levels of protection, whereas a 1/100 dose resulted in mortality and virus shedding by 7 dpi. Moreover, immunity induced by the two vaccines was long lasting, with HI titers of >7 log2 against the vaccine strain remaining after 6 months. Thus, the two vaccine candidates show protective efficacy and can be used to update the AI national antigen bank.

To date, nephrotoxicity in new drug development has been evaluated through two-dimensional culture of representative cell lines, such as HK-2 and human proximal tubule epithelial cells (hPTECs). Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of nephrotoxicity. Here, we established proximal tubule cell lines from immortalized mixed primary renal cells and generated functional proximal tubule cell spheroids, which expressed all apical basolateral transporters and showed epithelial polarity. Moreover, they showed a more sensitive drug response than hPTECs, which have been commonly used as in vitro kidney models. Taken together, the proximal tubule cells described in this study provide a more stable, reproducible, and accurate in vitro kidney model for predicting nephrotoxicity, which could help early compound development.