Presenilin-2 knock-In mice show severe depressive behavior via DVL3 downregulation.

INTRODUCTION: Alzheimer's disease (AD) is the most common form of dementia. Depression is one of the most critical psychiatric complications of AD, and 20%-30% of patients with AD experience symptoms of depression. Phospho-glycogen synthase kinase-3 beta (GSK3ß) is known to be associated with AD and depression. Furthermore, the role of disheveled (DVL) is known to regulate GSK3ß. Moreover, presenilin-2 (PS2) and DVL have cross-talk with each other. Also, it is widely hypothesized that stress leads to hypersecretion of cortisol and is thus associated with depression. Dickkopf WNT signaling pathway inhibitor-1 (DKK-1) is a crucial factor regulating depression and both amyloid beta (Aß) and phosphorylation of tau are widely known as a biomarker of AD. METHODS: To investigate the relationship between AD and depression, and possible pathways connecting the two diseases, we examined memory function and depression-related behavior test results in PS2 knock-in AD mice (PS2 MT). Next, we confirmed that there are relationships between DVL, depression, and cognitive disease through the comparative toxicogenomics database (https://ctdbase.org) and STRING (https://string-db.org) database. RESULTS: PS2 knock-in mice showed much more severe memory impairment and depression than PS2 wild-type mice (PS2 WT). In AD-related behavioral experiments, PS2 MT mice showed more memory dysfunction compared with PS2 WT group mice. Moreover, Aß and phosphorylation of tau showed higher expression in PS2 MT mice than in PS2 WT mice. Depression-related behavioral tests showed that PS2 MT mice exhibited more depressive behaviors than PS2 WT mice. Furthermore, both higher cortisol levels and higher expression of DKK-1 were found in PS2 MT mice relative to PS2 WT mice. The results indicated that there is a relationship between DVL and the release of AD-related mediators and expression of the depression-related glucocorticoid receptor and DKK-1. In the PS2 knock-in group, DVL was significantly decreased compared with the PS2 WT group. CONCLUSION: Depression increases the risk of developing AD and other forms of dementia. Recent evidence indicates that depression symptoms could trigger changes in memory and thinking over time. However, it is recognized that there are no drugs to facilitate a full recovery for both AD and depression. However, our results suggest that AD and depression could be associated, and DVL could be a significant target for the association between AD and depression.

Differences in Growth and Dietary and Nutrient Intake Patterns by Breastfeeding Status Over One Year Among Korean Children Aged 24-35 Months.

BACKGROUND: A previous national study found that Korean children who were breastfed for at least one year had lesser weight gain, lower protein, calcium, and iron intake relative to calories, and different dietary patterns in the second year of life, compared with children weaned before 12 months of age or those who were never breastfed. Therefore, this study aimed to investigate whether growth status, dietary and nutrient intake patterns differed by prolonged breastfeeding (PBF) experience even in the third year of life, when weaning is considered complete. METHODS: This cross-sectional study was based on the data of children aged 24 to 35 months from the National Health and Nutrition Examination Survey (2010-2020). Data on anthropometry, dietary behavior, food and nutrient intake, maternal education, and household income were extracted to analyze the association between PBF and growth, dietary and nutrient intake patterns. RESULTS: In the final analysis, 31.6% of the 931 children with a birth weight of ≥ 2.5 kg continued to breastfeed for at least 12 months of age, and their mean breastfeeding (BF) duration was 15.9 months. Children with PBF had significantly less postnatal weight gain than those without (P = 0.006). Regarding food group intake, PBF was significantly associated with lower legume and soy product intake (ß [95% confidence interval], -10.688 [-19.314, -2.062], P = 0.015) and higher fruit intake (32.978 [3.349, 62.608], P = 0.029), after adjusting for sex, age in month, total caloric intake, maternal education and household income. Regarding nutrient intake, after adjusting for these variables, PBF had significantly associated with higher dietary fiber (ß [95% CI], 1.607 [0.218, 2.996], P = 0.023), iron (0.848 [0.317, 1.380], P = 0.002) and niacin (0.728 [0.222, 1.235], P = 0.005) intake and was significantly associated with lower saturated fatty acid intake (-1.217 [-2.364, -0.071], P = 0.037) and percentage of energy from fat (-1.351 [-2.666, -0.035], P = 0.044). CONCLUSION: Even in the third year of life, children who have been breastfed for over one year continue to have relatively slow growth. However, they do appear to have better intake of some beneficial nutrients, which may be attributed to healthier dietary intake patterns in children with PBF. The results of this study can be used to support the recommendation of long-term BF for Korean infants and toddlers.

Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis.

Background: Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022. Methods: We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings: A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I2 = 95·58% versus 2015-2022; 27.91 [24.86-30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias. Interpretation: AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa. Funding: National Research Foundation of Korea.

The Current Status of Prolonged Breastfeeding and Its Related Factors in Korean Infants and Their Mothers: A Nationwide Cross-Sectional Study.

BACKGROUND: International authorities recommend prolonged breastfeeding (PBF) for 12-24 months or more with 6 months of exclusive breastfeeding (EBF). Based on the Korean National Health and Nutrition Examination Survey (KNHANES) data, this study attempted to help encourage and educate breastfeeding (BF) over 1 year by investigating long-term BF trends and related factors in Korean infants and their mothers. METHODS: This cross-sectional study was based on data on children aged 12-23 months and their mothers from 2010 to 2020. BF rates were compared between KNHANES V (2010-2012), KNHANES VI (2013-2015), KNHANES VII (2016-2018), and part of KNHANES VIII (2019-2020). In addition, data related to mothers and infants, including demographics, socioeconomic, educational, and health status, were collected, and their association with BF status was analyzed. RESULTS: Of the 933 infants included in the study, the proportions achieving full BF at 6 months of age and PBF at 12 and 18 months were 34.8%, 33.7%, and 7.1%, respectively. Over the past 10 years, the trends of all three BF practices have significantly decreased since 2016 (P < 0.001). Of the 849 infants whose maternal data were available, multiple logistic regression analysis showed that EBF for 6 months (defined as full BF at 1, 3, and 6 months of age) positively correlated with maternal and infants' factors such as unemployed status, past BF experience, no history of drinking, and infants' birth weight of ≥ 2.5 kg. The mother's education level, particularly the nutrition label impact, current employment status, and smoking and drinking status, were significantly associated with PBF for ≥ 12 months but were not related to PBF for ≥ 18 months, except for drinking status. CONCLUSIONS: In Korea, the long-term BF rate of ≥ 12 months has declined in the past 10 years, and BF becomes rare after 18 months. Higher maternal interest in nutrition information appears to be driving access to PBF over 12 months than EBF for 6 months or PBF over 18 months. To promote PBF over 12 months in Korea, it may be helpful to strengthen nutrition education that specifically emphasizes the benefits of PBF along with EBF, especially during infant health examinations.

Growth, Nutritional Status, and Dietary Intake Patterns Associated With Prolonged Breastfeeding in Young Korean Children: A Nationwide Cross-Sectional Study.

BACKGROUND: Although the optimal duration of breastfeeding remains unclear, breastfeeding is generally recommended exclusively for the first 6 months of life, which continues into late infancy. However, the awareness regarding the effects of long-term breastfeeding is relatively low compared with that of breastfeeding in early infancy. We aimed to investigate the growth and nutritional characteristics of the children with prolonged breastfeeding (PBF) over 1 year. METHODS: This cross-sectional study was based on the data of children aged 12 to 23 months from the National Health and Nutrition Examination Survey (2010-2020) conducted by the Korean Center for Disease Control and Prevention. Data on anthropometric measurements, dietary behavior, and food and nutrient intake were extracted, and the association between PBF and growth, nutritional status, and dietary patterns were analyzed. RESULTS: Of the 872 children with a birth weight of ≥ 2.5 kg in the final analysis, 34.2% continued breastfeeding over 12 months of age, and their median breastfeeding duration was 14.2 months. Children with PBF were more likely to have lower current body weight (P < 0.001) and weight gain (P < 0.001), lower daily protein (P = 0.012), calcium (P < 0.001), and iron (P < 0.001) intake per calorie compared with children weaned by 12 months of age or those who were never breastfed. Furthermore, they were started on complementary food at 6 months or later rather than 4-5 months (P < 0.001), consumed cow's milk earlier (P = 0.012), and consumed probiotics as dietary supplements (P < 0.001) significantly less commonly. When comparing the intake of food groups, children with PBF had a significantly higher intake of cereals and grains (P = 0.023) and fruits (P = 0.020) and a significantly lower intake of bean products (P = 0.020) and milk and dairy products (P = 0.003). CONCLUSION: Korean children who continued breastfeeding over 12 months of age showed distinct characteristics in terms of growth, nutritional status, and dietary patterns in the second year of life compared to children who did not. Long-term additional research on their growth and nutritional status may be needed; however, these findings are significant as important fundamental data for nutritional counseling to establish healthy PBF.

Chitinase 3 like 1 deficiency ameliorates lipopolysaccharide-induced acute liver injury by inhibition of M2 macrophage polarization.

Chitinase 3-like-1 protein (CHI3L1) is involved in various infectious diseases, especially sepsis. Aberrant CHI3L1 expression potentially plays a critical role in chronic inflammation because a considerable number of macrophages are associated with immune/inflammatory diseases. In this study, we examined the effect of CHI3L1 on hepatic sepsis injury using a lipopolysaccharide (LPS)-induced model. LPS-treated CHI3L1 knockout (KO) mice exhibited a higher survival rate than LPS-treated CHI3L1 wild-type (WT) mice. In addition, hepatic injury-related enzyme levels (aspartate transaminase, alanine transaminase, and lactate dehydrogenase) decreased in CHI3L1 KO mice sera, suggesting attenuated LPS-induced septic liver damage in CHI3L1 KO mice. A greater reduction in the mRNA and protein expressions of M2 polarization markers, such as MRC1, ARG1, IL-10, and IL-4, was observed in LPS-induced CHI3L1 KO mice livers than in LPS-induced WT mice livers. Nonetheless, no change in the mRNA and protein expressions of M1 polarization markers, such as INOS, CD86, TNF-α, and IL6, was noted in LPS-induced CHI3L1 KO mice livers compared with those in LPS-induced WT and KO mice. Similar to the in vivo scenario, liver CHI3L1 depletion in LPS-treated HEP3B cells significantly decreased M2 polarization marker protein expression. However, M1 polarization marker protein expression did not differ significantly. These results suggest that CHI3L1 depletion decreases M2 macrophage polarization, and this effect is potentially associated with the alleviation of liver sepsis in CHI3L1 KO mice.

Distinct Clinical and Laboratory Features of COVID-19 in Children During the Pre-Delta, Delta and Omicron Wave.

BACKGROUND: The SARS-CoV-2 variants of concern exhibit distinct features in terms of transmissibility and virulence. This study compared the clinical characteristics of COVID-19 in children during pre-Delta, Delta and Omicron waves. METHODS: Medical records of 1163 children <19 years of age with COVID-19 admitted to a designated hospital in Seoul, South Korea, were analyzed. Clinical and laboratory findings during the pre-Delta (March 1, 2020, to June 30, 2021; 330 children), Delta (July 1, 2021, to December 31, 2021; 527 children) and Omicron (January 1, 2022, to May 10, 2022; 306 children) waves were compared. RESULTS: Children during the Delta wave were older and had a higher proportion of fever ≥5 days and pneumonia than children during the pre-Delta and Omicron waves. The Omicron wave was characterized by younger age and a higher proportion of fever ≥39.0 °C, febrile seizure and croup. More children <2 years of age and adolescents aged 10 to <19 years experienced neutropenia and lymphopenia, respectively, during the Delta wave. Children aged 2 to <10 years had a higher incidence of leukopenia and lymphopenia during the Omicron wave. CONCLUSIONS: Distinct features of COVID-19 were observed in children during the Delta and Omicron surges. Continuous scrutiny of the manifestations of variants of concern is needed for appropriate public health response and management.

Snake venom induces an autophagic cell death via activation of the JNK pathway in colorectal cancer cells.

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.

Maternal lipid profiles vs. fetal growth and cord blood hematopoietic cells: weak associations in healthy Korean newborn-mother pairs.

BACKGROUND: 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. METHODS: 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 CD34+ cell concentrations of CB as markers of hematopoietic progenitor cell (HPC) contents. We also analyzed maternal lipid levels and investigated their associations with BW, TNCs and CD34+ cells. RESULTS: Maternal triglycerides (TG) showed a significant positive association with BW and CD34+ cells, and low-density lipoprotein (LDL) showed a negative association with BW and CD34+ cells. Though not statistically significant, higher maternal TG showed a tendency toward higher levels of TNCs. Maternal TG was independently and positively correlated with BW, and maternal LDL was independently and negatively correlated with CD34+ cells, although the impacts were not as strong, as indicated by small beta coefficients (0.157 and -0.226, respectively). CONCLUSIONS: We 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.

A Natural CHI3L1-Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals.

Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.

Bee Venom Triggers Autophagy-Induced Apoptosis in Human Lung Cancer Cells via the mTOR Signaling Pathway.

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.

Nationwide "Pediatric Nutrition Day" survey on the nutritional status of hospitalized children in South Korea.

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.

A Nomogram for Predicting Non-Alcoholic Fatty Liver Disease in Obese Children.

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<0.05) as determined using homeostatis model assessment of insulin resistance (HOMA-IR). In our multivariate logistic regression analysis, elevated serum ALT, γGT, and triglyceride levels were significantly related to NAFLD development. The nomogram was established using γGT, uric acid, triglycerides, HOMA-IR, and ALT as predictors of NAFLD probability. CONCLUSION: The newly developed nomogram may help predict NAFLD risk in obese children. The nomogram may also allow for early NAFLD diagnosis without the need for invasive liver biopsy or expensive liver imaging, and may also allow clinicians to intervene early to prevent the progression of NAFLD to become a more advanced liver disease.

Development of Hepatocellular Carcinoma in Patients with Glycogen Storage Disease: a Single Center Retrospective Study.

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.

Association of IL23R Variants With Crohn's Disease in Korean Children.

Background: The interleukin 23 receptor gene (IL23R) is strongly associated with Crohn's disease (CD). It is unknown whether genetic variations in IL23R determine susceptibility for pediatric CD in Asian populations. Here, we investigated the association between IL23R variants and CD in Korean children. Methods: Four single nucleotide polymorphisms (SNPs) of IL23R [rs76418789 (G149R), rs1004819, rs7517847, and rs1495965] were genotyped in 141 children with CD and 150 controls using DNA direct sequencing. The risk allele and genotype frequencies were compared between patients and controls. The association between clinical phenotypes and genotypes of patients was also analyzed. Results: Two IL23R SNPs, rs76418789 (G149R), and rs1495965, were associated with CD in Korean pediatric patients as defense and risk loci, respectively. The odds ratio (OR) for rs76418789 (G149R) and rs1495965 was 0.409 (95% confidence interval [CI], 0.177-0.944; p = 0.031) and 1.484 (95% CI, 1.070-2.059; p = 0.018), respectively. Patients with the homozygous G allele of rs1495965 showed higher CD risk than those with other genotypes (GG vs. AA: OR, 2.256; 95% CI, 1.136-4.478; p = 0.019; GG vs. GA+AA: OR, 2.000; 95% CI, 1.175-3.404; p = 0.010). Additionally, they were more likely to have relatively invasive disease behavior of stenosis and/or penetration than simple inflammation (OR, 2.297; 95% CI, 1.065-4.950; p = 0.032). Conclusions: This is the first study reporting IL23R variants in Asian pediatric patients with CD. IL23R was significantly associated with Korean pediatric CD, and the rs1495965 may influence the clinical features of CD in Korean children.

Association Between Vitamin D Deficiency and Suspected Nonalcoholic Fatty Liver Disease in an Adolescent Population.

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 <20 ng/mL and suspected NAFLD was defined as an alanine transaminase 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.

Multiplex Ligation-dependent Probe Amplification Analysis Subsequent to Direct DNA Full Sequencing for Identifying ATP7B Mutations and Phenotype Correlations in Children with Wilson Disease.

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.

Prevalence and risk factors of elevated alanine aminotransferase among Korean adolescents: 2001-2014.

BACKGROUND: An elevated alanine aminotransferase (ALT) level is a surrogate marker of non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in adolescents. The majority of previous NAFLD studies in adolescents were performed in selected obese populations or had a cross-sectional design without a time-trend analysis. The purpose of this study was to estimate the prevalence and time trends of elevated ALT levels in a general adolescent population and to identify factors associated with ALT elevation. METHODS: We analysed data of adolescent participants (aged 10-18 years) from the Korean National Health and Nutrition Examination Survey 2001-2014, a representative sample of the general population in South Korea. Suspected NAFLD was defined as ALT elevation (> 30 U/L) without hepatitis B surface antigen. In all statistical analyses, sampling weight- and design-based data were used. RESULTS: ALT was elevated in 5.3% (standard error: 0.3%) of the study population of adolescent participants (N = 8455). No significant trends were found from 2001 to 2014 in the prevalence of elevated ALT among male and female adolescents. In multiple logistic regression analysis, elevated ALT was independently associated with sex (odds ratio [OR] male versus female 4.5; 95% CI, 3.3-6.2), obesity (OR 7.6; 95% CI, 5.3-11.0), and truncal obesity (OR 2.5; 95% CI, 1.8-3.5). Furthermore, male sex, obesity, truncal obesity and high household income level were associated with log-transformed ALT levels in multiple regression analysis. CONCLUSIONS: In Korean adolescents of both genders, the prevalence of elevated ALT levels was stable from 2001 to 2014. This study has revealed that sex, obesity, truncal obesity and household income level are associated with ALT elevation in adolescents.

Different Age Distribution between Campylobacteriosis and Nontyphoidal Salmonellosis in Hospitalized Korean Children with Acute Inflammatory Diarrhea.

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.