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Snake venom contains many proteins that help treat or prevent thrombosis, cardiovascular disease, and cancer, and many studies have been reported in this regard. It has recently been reported that autophagy exerts anticancer effects by inducing tumor cell death and inhibiting cell growth. In this study, we investigated the effect of snake venom on autophagy. Unlike normal colon cells, LC3-II protein levels and LC3 puncta accumulation are increased in snake venom-treated colorectal cancer cells. Inhibition of autophagy by treating cells with hydroxychloroquine, an autophagy inhibitor, prevented snake venom-induced cell death, indicating that snake venom indeed induces autophagic cell death in human colorectal cancer cells. In addition, we demonstrated that activated JNK, and not mTOR signaling, is an upstream effector controlling autophagy. Pretreatment with SP600125, a JNK inhibitor, reversed snake venom-induced autophagy and cell death, indicating that JNK plays a critical role in snake venom-induced autophagy. This study demonstrated that snake venom can function as an anticarcinogenby induction autophagy.

BACKGROUND/OBJECTIVES To evaluate the nutritional status and prevalence of malnutrition in hospitalized children at admission and during hospitalization in South Korea. SUBJECTS/METHODS This first cross-sectional nationwide "Pediatric Nutrition Day (pNday)" survey was conducted among 872 hospitalized children (504 boys, 368 girls; 686 medical, 186 surgical) from 23 hospitals in South Korea. Malnutrition risk was screened using the Pediatric Yorkhill Malnutrition Score (PYMS) and the Screening Tool Risk on Nutritional status and Growth. Nutritional status was assessed by z-scores of weight-for-age for underweight, weight-for-height for wasting, and height-for-age for stunting as well as laboratory tests. RESULTS At admission, of the 872 hospitalized children, 17.2% were underweight, and the prevalence of wasting and stunting was 20.2% and 17.3%, respectively. During hospitalization till pNday, 10.8% and 19.6% experienced weight loss and decreased oral intake, respectively. During the aforementioned period, fasting was more prevalent in surgical patients (7.5%) than in medical patients (1.6%) (P < 0.001). According to the PYMS, 34.3% and 30% of the children at admission and on pNday, respectively, had a high-risk of malnutrition, requiring consultation with the nutritional support team (NST). However, only 4% were actually referred to the NST during hospitalization. CONCLUSIONS Malnutrition was prevalent at admission and during hospitalization in pediatric patients, with many children experiencing weight loss and poor oral intake. To improve the nutritional status of hospitalized children, it is important to screen and identify all children at risk of malnutrition and refer malnourished patients to the multidisciplinary NST for proper nutritional interventions.

In oriental medicine, bee venom has long been used as a therapeutic agent against inflammatory diseases. Several studies have reported that isolated and purified bee venom components are effective in treating dementia, arthritis, inflammation, bacterial infections, and cancer. In previous studies, we reported that bee venom inhibits cell growth and induces apoptotic cell death in lung cancer cells. In the present study, we assessed whether bee venom affects autophagy and thereby induces apoptosis. Bee venom treatment increased the levels of autophagy-related proteins (Atg5, Beclin-1, and LC3-II) and the accumulation of LC3 puncta. We found that bee venom could induce autophagy by inhibiting the mTOR signaling pathway. In addition, we found that hydroxychloroquine (HCQ)- or si-ATG5-induced autophagy inhibition further demoted bee venom-induced apoptosis. Bee venom-induced autophagy promotes apoptosis in lung cancer cells and may become a new approach to cancer treatment.

Purpose Vitamin D deficiency is a condition widespread throughout the world. Recent studies have suggested that vitamin D deficiency was associated with obesity and metabolic syndrome. The purpose of the study was to examine the relationship between vitamin D deficiency and nonalcoholic fatty liver disease (NAFLD) in adolescents. Methods The data were obtained from the Korean National Health and Nutrition Examination Survey from 2008–2014. A total of 3,878 adolescents were included in the study. Vitamin D deficiency was defined as a 25-hydroxyvitamin D concentration 30 U/L. Results Vitamin D deficiency was noted in 78.9% of the studied population. Age, body mass index, waist circumference, and blood pressure, glucose, cholesterol, and triglyceride levels were significantly higher in adolescents with suspected NAFLD than in adolescents without suspected NAFLD, while the mean vitamin D level was significantly lower in adolescents with suspected NAFLD. The multivariate-adjusted odds of suspected NAFLD were higher with increased age, male gender, obesity, and metabolic syndrome. Individuals with vitamin D deficiency were at higher risk of suspected NAFLD (odds ratio, 1.77; 95% confidence interval, 1.07–2.95) after adjusting for age, gender, obesity, and metabolic syndrome. Conclusion Vitamin D deficiency was associated with suspected NAFLD, independent of obesity and metabolic syndrome, in adolescents.

Background This study primarily discusses the links and connections of imaginary creatures illustrations between two ancient books: "Classic of the Great Wilderness"(山海經) and "Strange Animals Book"(怪奇鳥獣図巻). And this study compares and analyses their similarities, and investigates on their historical links between China and Japan. The main aim of this study is to find the relation between two books, to explore the value of those ancient books and to investigate their potential of application to contemporary design and other areas. Methods Literature research: By studying the imaginary creatures illustrations of two books in libraries and museums, and reviewed imaginary creatures that appear in "Classic of the Great Wilderness" and "Strange Animals Book", and then analysed them on a comprehensive and detailed basis. Case research: Representative creatures that appear in both Chinese and Japanese versions were selected for the analysis and comparison. Comparative research: By comparing the images of the imaginary creatures that appear in the two books, the study analyzed their links and relations, and then discussed their heritage in innovating and developing the traditional culture. Result By comparing the images of the imaginary creatures that appear in the two books, the study found the relation between them, identified their similarities, and analyzed their differences. The imaginary creatures in "Classic of the Great Wilderness" gave a big influence to the creation of "Strange Animals Book" as a reference. The imaginary creatures after the integration of the Japanese local imaginary creatures culture system and gradually evolved into a variety of Japanese imaginary creatures images that some are still active now. Although "Classic of the Great Wilderness" was written hundreds of years ago, it remains a creative gem that offers insight for innovation. A close correlation exists between valuable cultural inheritance and innovation. Conclusion According to the description and images of various imaginary creatures in "Classic of the Great Wilderness", the imaginary creatures are used as a reference in the creation of "Strange Animals Book" for depicting cultural elements from China. A number of them have been disseminated through local Japanese culture, and many classic Japanese monsters images are still well known today, such as Tengu(天狗). And with the evolution of these traditional images, they were known and loved by more people, and were used in various fields. Important traditional books such as “The Classic of the Great Wilderness” and "Strange Animals Book" are priceless sources for creating contemporary design and inspiration. Those ancient books left a great wealth on the art of thinking and imagination, so they are worth letting more people learn and study their mystery.

Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Background Glycogen storage disease (GSD) is an inherited disorder leading to abnormal glucose metabolism and glycogen accumulation, and is associated with various complications including hepatic adenoma and hepatocellular carcinoma. The aim of this study was to analyze the risk factors for hepatic adenoma and its malignant change, and the hepatocellular carcinoma-free survival rate in patients with GSD who developed adenoma. Methods A total of 72 patients with GSD who were enrolled from March 1982 to September 2013 at Seoul National University Children's Hospital were retrospectively analyzed, and the median follow-up period was 19.2 years. Results Thirty-two patients (44.4%) developed hepatic adenoma at an age range of 7.9–26.3 years (median, 14.3 years). Among the 32 patients with hepatic adenoma, 4 patients (12.5%) developed hepatocellular carcinoma on an average interval of 6.7 years between the diagnosis of adenoma and the development of hepatocellular carcinoma. GSD type I and portacaval shunt operation were found to be the risk factors for hepatic adenoma development. The hepatocellular carcinoma-free survival rate at 10 years from adenoma development was 82%. Conclusion The present study found that portacaval shunt operation increases the risk of development of hepatic adenoma in GSD patients, especially in GSD type I. The hepatic adenoma in GSD patients has a potential of malignant transformation, which should be keep in mind in follow-up process of the disease., Graphical Abstract

Few studies have explored the association of oral bisphosphonate exposure and gastrointestinal cancer within Asian populations. In this study, we investigated 45,397 Korean women from the nationwide population-based cohort from 2002 to 2013. Oral bisphosphonate exposure did not appear to be associated with elevated or reduced risk for gastrointestinal cancer. While several studies suggested increased risk in upper gastrointestinal (GI) cancer or reduced risk in colorectal cancer upon bisphosphonate exposure, the association is less explored within Asian populations. We investigated the effect of oral bisphosphonate exposure on the risk of GI cancers within a nationwide population-based cohort. This study used two separate cohorts. The first cohort included 45,397 women aged 60 years or older from the National Health Insurance Service-Health Screening Cohort during 2002–2013. Participants were classified into bisphosphonate users and non-users based on drug exposure during 2002–2007, and followed-up from the index date of January 1, 2008. The second cohort included 25,665 newly diagnosed osteoporosis patients who started taking oral bisphosphonate during 2003–2008. After 4 years of drug exposure period, patients were separated into quartiles based on cumulative oral bisphosphonate exposure. Participants were followed-up until December 31, 2013 for GI cancer, stomach cancer, and colorectal cancer. Cox proportional hazard regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the cancer risks. Compared to bisphosphonate non-users, no significant risk difference was observed among bisphosphonate users on GI (HR 1.06; 95% CI 0.87–1.28), stomach (HR 1.11; 95% CI 0.85–1.47) and colorectal cancers (HR 1.04; 95% CI 0.79–1.37). Among bisphosphonate users, increasing doses of bisphosphonate exposure was not associated with elevated or reduced risk for GI cancer (p for trend 0.573). Oral bisphosphonate use did not appear to be associated with elevated or reduced risk for GI cancers.

We aimed to define the maternal lipid profiles that are associated with fetal growth and cord blood (CB) hematopoietic cells in healthy Korean full-term newborns.A total of 608 fetal-maternal pairs were enrolled; mothers voluntarily donated CB with informed consent. We analyzed birth weight (BW) as a marker of fetal growth, and we examined total nucleated cells (TNCs) and CD34Maternal triglycerides (TG) showed a significant positive association with BW and CD34We were able to investigate the association of maternal lipid profiles with BW and CB HPCs in healthy Korean newborn-mother pairs in this study. Both BW and the HPC contents showed independent associations with maternal TG and LDL, although the effect of maternal lipid levels on fetal growth and HPCs was not strong in the normal healthy population. Because maternal lipid levels were assessed once in the healthy fetal-maternal pairs, we could not investigate those associations across pregnancy.

Background Reference intervals need to be established according to age. We established reference intervals of hematology and chemistry from community-based healthy 1-yr-old children and analyzed their iron status according to the feeding methods during the first six months after birth. Methods A total of 887 children who received a medical check-up between 2010 and 2014 at Boramae Hospital (Seoul, Korea) were enrolled. A total of 534 children (247 boys and 287 girls) were enrolled as reference individuals after the exclusion of data obtained from children with suspected iron deficiency. Hematology and clinical chemistry analytes were measured, and the reference value of each analyte was estimated by using parametric (mean±2 SD) or nonparametric methods (2.5-97.5th percentile). Iron, total iron-binding capacity, and ferritin were measured, and transferrin saturation was calculated. Results As there were no differences in the mean values between boys and girls, we established the reference intervals for 1-yr-old children regardless of sex. The analysis of serum iron status according to feeding methods during the first six months revealed higher iron, ferritin, and transferrin saturation levels in children exclusively or mainly fed formula than in children exclusively or mainly fed breast milk. Conclusions We established reference intervals of hematology and clinical chemistry analytes from community-based healthy children at one year of age. These reference intervals will be useful for interpreting results of medical check-ups at one year of age.

Purpose Non-alcoholic fatty liver disease (NAFLD) ranges in severity from simple steatosis to steatohepatitis. Early detection of NAFLD is important for preventing the disease from progressing to become an irreversible end-stage liver disease. We developed a nomogram that allows for non-invasive screening for NAFLD in obese children. Methods Anthropometric and laboratory data of 180 patients from our pediatric obesity clinic were collected. Diagnoses of NAFLD were based on abdominal ultrasonographic findings. The nomogram was constructed using predictors from a multivariate analysis of NAFLD risk factors. Results The subjects were divided into non-NAFLD (n=67) and NAFLD groups (n=113). Factors, including sex, body mass index, abdominal circumference, blood pressure, insulin resistance, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γGT), uric acid, triglycerides, and insulin, were significantly different between the two groups (all p

Background Mutations in ATP7B cause Wilson disease (WD). However, direct DNA full sequencing cannot detect all mutations in patients with WD. Multiplex ligation-dependent probe amplification (MLPA) analysis is reportedly useful in increasing the diagnostic yield in other genetic disorders with large deletions or insertions. The aim of this study was to evaluate whether the detection rate of ATP7B mutations can be increased by using MLPA. Methods We enrolled 114 children with WD from 104 unrelated families based on biochemical tests and direct DNA full sequencing. The patients with one or zero mutant allele were investigated using MLPA. We analyzed phenotypic correlations. Results Total allele frequency by full sequencing was 87.5%. Full sequencing revealed two mutant alleles in 80 of 104 unrelated children. One mutant allele was detected in 22 children, and no mutations were found in two children. Novel mutations including small deletions with frameshift mutations were identified by DNA sequencing. MLPA revealed no gross deletion or duplication in 24 children with one or zero mutant alleles. The number of detected mutations was not associated with hepatic manifestation, age of onset, Kayser-Fleischer ring, ceruloplasmin, and urinary Cu concentrations. Conclusion MLPA showed a limited role to increase the mutation detection rate in children who do not receive a definite genetic diagnosis of WD through DNA full sequencing. This finding suggests that large deletions or duplications might be extremely rare in WD. Further development is needed to improve the genetic diagnosis of WD., Graphical Abstract

Objective To investigate relationships among oral mucosal epithelial MUC1 expression, salivary stress markers, and female gonadal hormones throughout the menstrual cycle. Subjects and Methods Thirty healthy women (25.9 ± 2.1 years) with regular menstrual cycle were included. Unstimulated (UWS) and stimulated whole saliva (SWS) were collected during the menstrual cycle. The expression level of oral mucosal MUC1 was analyzed. 17β-Estradiol, progesterone, dehydroepiandrosterone (DHEA), cortisol, chromogranin A (CgA), and blood contamination levels were measured from UWS and SWS. Results Significant positive correlations were observed between 17β-estradiol and DHEA in UWS, cortisol and CgA in UWS, MUC1 expression and DHEA in SWS, and among cortisol, progesterone, and DHEA in UWS and SWS. Significant negative correlations were observed between MUC1 and cortisol/DHEA ratio in UWS and SWS. When each phase was analyzed individually, MUC1 expression showed significant negative correlations with cortisol, progesterone, and cortisol/DHEA ratio in UWS and with progesterone and cortisol/DHEA ratio in SWS during the mid-luteal phase. A significant negative correlation was also observed between MUC1 and cortisol/DHEA ratio in UWS during the late luteal phase. Conclusions Stress-related psychoendocrinological interactions throughout the menstrual cycle resulted in a decrease in oral mucosal epithelial MUC1 expression and a weakening of oral mucosal defense.

Although statin is one of the most widely used drugs worldwide, the association between statin use and hepatocellular carcinoma (HCC) risk remains controversial. This study aims to investigate the association between statin use and risk of HCC in a large scale population-based prospective cohort. We selected participants aged >40 years in 2002 whose health examination data were available from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. We collected statin exposure data and medical information of the population in the database over 5 years (2002–2006), and followed up eligible participants for HCC development over the next 7 years (2007–2013). We used Cox proportional hazard regression models to calculate the hazard ratios of statin use and HCC risk, after adjusting for sex, age, incoming status, disability, body mass index, smoking status, alcohol consumption, physical activity, comorbidity, underlying liver disease, and medication use. Overall, 443,239 participants were included in the analysis, including 3,147 cases of HCC during the observation period. The adjusted hazard ratio for HCC in statin users was 0.66 (95% confidence interval [CI], 0.56–0.77), indicating a 34% risk reduction in a dose-response manner (P for trend < 0.001). Sensitivity analysis showed a reduced risk of HCC in statin users in all subgroups, in terms of age and sex, as well as a stronger risk reduction in patients with underlying liver disease. In conclusion, statin use is associated with a reduced risk of HCC in a dose-response manner.

Even low levels of toxic metal exposure (As, Cd, Hg, and Pb) in infancy might be harmful to children’s development. This study investigated toxic metal exposure on healthy weaning-age infants and its relationship with growth, diet, and iron/anemia status. The weight, height, head circumference, whole blood levels of four toxic metals, hemoglobin, and serum ferritin of healthy infants was measured. Among 210 infants with a median age of 11.4 months (interquartile range: 10.5–12.0), the median levels of As, Cd, Hg, and Pb were 1.2 μg/L, 0.05 μg/L, 0.8 μg/L, and 0.83 μg/dL, respectively. In adjusted linear regression models, post-birth weight gain (Pb) and current head circumference (As, Pb) were negatively associated with toxic metal levels. In multiple linear regression or logistic regression analysis, the duration of breastfeeding (all four metals), perceived adequacy of rice-based food intake (As), regular fish intake (As, Hg), and iron deficiency with/without anemia (Cd, Pb) were associated with increased toxic metal levels. Although levels of toxic metals may not usually be high in this population, individual exposure risk may need to be assessed after considering the type of feeding or intake of complementary foods and the iron/anemia status while evaluating growth status during late infancy.

We evaluated the relationship between mean platelet volume (MPV) and characteristics of 10,577 cord blood (CB) units in a public CB bank in Korea. Blood group O has the highest MPV (P= 0.002). MPV correlated with CB volume (r=0.121), Hb (r=0.377), WBC (r=0.111), TNCs (r=0.110), CD34+ cell (r=0.174), CD34+ cells/TNCs (r=0.157), gestational age (r= −0.102), and birth weight (r=0.023); (P<0.001in all). MPV may be one of the useful decision parameters of process priority in CB bank.

In the present study, we evaluated the correlation between iron deficiency (ID) and zinc deficiency (ZD) and explored the demographic, anthropometric, and feeding-related factors associated with hypozincemia and hair zinc content in weaning infants. Infants aged 6-24 months were recruited, their feeding history was recorded, and their heights and weights were measured. Hemoglobin content, serum iron/total iron-binding capacity, and ferritin and zinc concentrations of serum and hair (using inductively coupled plasma-mass spectroscopy) were assessed. Among 101 infants, 64 (63.4 %) infants exhibited ID. The median serum zinc concentration in iron-deficient infants was lower than that in non-iron-deficient infants, respectively, 73.5 μg/dL (interquartile range [IQR], 65.0-83.8) vs. 87.0 μg/dL (IQR, 77.5-97.0; p = 0.001). The frequency of hypozincemia was also significantly higher in the iron-deficient group than in the non-iron-deficient group (21 out of 64 [32.8 %] vs. 4 out of 37 [10.8 %], respectively; p = 0.014). In multiple regression analysis, the risk of hypozincemia was significantly increased in infants with ID (p = 0.026), mildly underweight infants (weight-for-age Z score -1; p = 0.034), and infants with mild wasting (weight-for-height Z score -1; p = 0.028). Hair zinc concentrations (n = 81) were not significantly associated with ID status (p 0.1); however, there was an inverse relationship between hair zinc concentrations and age of infants (r = -0.250; p = 0.024). In weaning infants, ID is a risk factor for hypozincemia. Hair zinc concentrations appeared to decrease as the age of infants increased during late infancy. Further large-scale studies are needed to validate the relationship between hypozincemia and mild degrees of weight gain impairment in this age group.

Objectives The aim of the study was to investigate the previously unexplored diversity of neonatal intestinal microbiota and monitor early intestinal colonization patterns in Korean preterm infants using high-throughput pyrosequencing technology combined with 16S rDNA-based molecular methods. Subjects and methods A total of 46,369 partial 16S rDNA sequences obtained from 30 fecal samples serially taken from 10 very-low-birth weight preterm infants were analyzed. Results A significant proportion of the molecular species (21.9%) was found to be unclassified. The pathogenic or potentially pathogenic molecular species belonging to the classes Gammaproteobacteria and Bacilli were predominant during the entire observation period. Anaerobic or nonpathogenic molecular species belonging to the class Clostridia (except Clostridium difficile) and phyla Bacteroidetes were ubiquitous even within 72 hours after birth. The proportion of these species increased significantly at 1 month of age. The most ubiquitous and abundant major molecular genera common to all of the postnatal ages were Escherichia, Enterobacter, Enterococcus, Veillonella, Serratia, Staphylococcus, Roseburia, Acinetobacter, Citrobacter, Bacteroides, Faecalibacterium, Blautia, and Streptococcus. Conclusions The diversity and dynamic nature of intestinal bacterial colonization in very-low-birth weight preterm infants were revealed using pyrosequencing technology. The results of the present pilot study may provide a basis to consider when investigating or interpreting the role of intestinal microbiota in certain preterm infant diseases such as necrotizing enterocolitis or systemic infection.

The main purpose of this report is to provide baseline gene frequencies of Knops blood group in the complement receptor 1 gene (CR1) in Korean population. In addition, possible relationship between the CR1 polymorphism and HLA specificities were studied, because the two systems had principal importance in immunity. CR1, which contains Knops antigens, was investigated by PCR-direct sequencing from 238 cord blood from Koreans. HLA data was archived from the enrolled cord blood units. Among the 7 SNPs, only 4843 (for KCAM antigen) and 4223 (for Yk(a)) nucleotide positions showed polymorphism. The genotype frequencies of KCAM were A/A (62.2%), A/G (33.2%), and G/G (4.6%); Yk(a) were C/C (29.4%), C/T (50%), and T/T (20.6%). KCAM (A/A) associated with HLA-DRB1(∗)13 (p=0.003, P(c)=0.0513); KCAM (G/G) with HLA-A(∗)30 (p

We investigated recent epidemiologic trends regarding campylobacteriosis vs. nontyphoidal salmonellosis (NTS), a previously known leading cause of bacterial enterocolitis in Korean children. Among 363 hospitalized children with acute inflammatory diarrhea, Campylobacter (18.7%) was the most frequently detected pathogen using multiplex polymerase chain reaction tests followed by Salmonella (15.4%). Children with campylobacteriosis were older than children with NTS (112.6 months [interquartile range (IQR) 66.0–160.1] vs. 53 months [IQR 31.0–124.0], P < 0.001) and had higher prevalences of abdominal cramping and stool hemoglobin. Campylobacteriosis may be suspected as a primary cause of acute inflammatory diarrhea in hospitalized school-aged Korean children and adolescents., Graphical Abstract

The present study investigated risk factors for iron deficiency (ID) and iron deficiency anemia (IDA) during late infancy, including feeding type and complementary feeding (CF) practice. Healthy term Korean infants (8–15 months) were weighed, and questionnaires regarding delivery, feeding, and weaning were completed by their caregivers. We also examined levels of hemoglobin, serum iron/total iron-binding capacity, serum ferritin, and mean corpuscular volume (MCV). Among 619 infants, ID and IDA were present in 174 infants (28.1%) and 87 infants (14.0%), respectively. The 288 infants with exclusively/mostly breastfeeding until late infancy (BFL) were most likely to exhibit ID (53.1%) and IDA (28.1%). The risk of ID was independently associated with BFL (adjusted odds ratio [aOR], 47.5; 95% confidence interval [CI], 18.3–122.9), male sex (aOR, 1.9; 95% CI, 1.2–2.9), fold weight gain (aOR, 2.6; 95% CI, 1.5–4.6), and perceived inadequacy of red meat intake (aOR, 1.7; 95% CI, 1.0–2.7). In addition to the risk factors for ID, Cesarean section delivery (aOR, 1.9; 95% CI, 1.1–3.2) and low parental CF-related knowledge (aOR, 2.8; 95% CI, 1.5–5.2) were risk factors for IDA. In conclusion, prolonged breastfeeding and perceived inadequacy of red meat intake may be among the important feeding-related risk factors of ID and IDA. Therefore, more meticulous education and monitoring of iron-rich food intake, such as red meat, with iron supplementation or iron status testing during late infancy if necessary, should be considered for breastfed Korean infants, especially for those with additional risk factors for ID or IDA., Graphical Abstract

We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (P < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (P < 0.001) and modified Vesikari score (P = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (P = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (P < 0.001). Viral co-infection and toxigenic C. difficile co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens., Graphical Abstract

Hepatitis B virus (HBV) vaccination is the most effective means of countering HBV-related morbidity and mortality, and individuals who do not respond to vaccination (non-responders) are problematic. The aim of the present study was to investigate associations between HLA and responsiveness to HBV vaccine in Korean infants. A total of 944 healthy Korean infants 9-12 months old were enrolled, and HLA distribution was compared among subgroups in accordance with the response to HBV vaccination. The HLA distribution of the subjects was similar to known Korean population data and did not deviate from the HWE proportions. The alleles that showed positive associations with non-responsiveness (10mIU/mL) or low antibody titer (100mIU/mL) were HLA-A*33, B62, DRB1*04, and DRB1*07, while the alleles A*02 and DRB1*08 showed negative associations. Among these alleles, B62, DRB1*07 and DRB1*08(-) showed significant associations with a poor or decreased response to vaccination even after correction (OR=1.83, 1.99, 5.63; pc0.05) and also showed dose effects. After stratification by other associated alleles at different loci, B62 and DRB1*07 were independently associated with non-responsiveness, but A*02(-) and DRB1*08(-) lost their individual associations. The combined association of A*02(-)-DRB1*08(-) and B62-DRB1*08(-) was significant (OR=25.2 and 24.5; pc0.05). Although the hierarchy is not clear, we can assume the following: (i) B62 and DRB1*07 have independent effects, (ii) DRB1*08(-) has a very strong and synergic effect, and (iii) there is probability of a third factor controlling A*02(-) and DRB1*08(-) with an effect on non-responsiveness to HBV vaccination in Korean infants.