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Background Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. Results During the program (2018–2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. Conclusions The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.

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.

Crohn’s disease is a chronic inflammatory disease that involves the upper and lower gastrointestinal tracts, including the oral cavity. For the conventional treatment of inflammatory bowel diseases, steroids are usually used as induction therapy, and azathioprine is used as maintenance therapy. Steroids are associated with various side effects. Under rare circumstances, they can even cause psychotic symptoms, and reports on steroid-induced psychosis in the pediatric population are few. Here, we report the first case of steroid-induced psychosis in a 16-year-old female with Crohn’s disease administered with steroids as induction therapy in South Korea. She showed psychotic symptoms, including auditory hallucination, loosening of association, and idea of reference, after 2 weeks of administering prednisolone 60 mg/day. One week after steroid discontinuation, the patient gradually recovered and was treated with quetiapine. Therefore, pediatricians should be aware of serious psychiatric adverse effects when administering corticosteroids for various indications.

The Food and Drug Administration (FDA) expanded the emergency use authorization for the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) for children aged 12-15 years on 10 May 2021. To date, less than a year has passed since vaccination against COVID-19 has been used in children and adolescents, and the overall effects and safety of these vaccines are still being assessed. The BNT162b2 vaccine originally had a favorable profile in 12-17-year-old recipients compared with older ages, and no serious adverse events had previously been reported. Despite various adverse events, the benefit of reducing the infection rate or the frequency of severe COVID-19 has been evaluated to outweigh the harm caused by COVID-19 vaccination. Additionally, several cases of sudden development of new-onset or relapsing glomerular diseases, including acute kidney injury (AKI), have been reported in adults following the BNT162b2 SARS-CoV-2 mRNA vaccine. Herein, we present two cases of adolescents who developed AKI following the second administration of the BNT162b2. These are the first pediatric cases of acute tubulointerstitial nephritis temporarily linked to SARS-CoV-2 vaccination.

Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94,Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

Purpose On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). Methods We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI

Purpose We investigated the association of effector memory (EM) CD8+ T cell and CD4+ T cell immunity with metabolic syndrome (MS). Methods Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8+ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4+ T cell subsets. Results Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 μU/mL, p

We report a rare case of Meckel's diverticulum in a boy who initially presented with chronic iron deficiency anemia (IDA) without any history of gastrointestinal (GI) bleeding at 8 years-old. Isolated small bowel Crohn's disease was suspected based on findings of small bowel ulcers on capsule endoscopy. At four years from initial presentation, he developed massive GI bleeding. Abdominal computed tomographic angiography and small bowel series revealed findings suggestive of Meckel's diverticulum. Meckel's diverticulum should be suspected in children with unexplained chronic IDA even in the absence of prominent GI bleeding and negative findings on repetitive Meckel's scans. Moreover, Meckel's diverticulum should be included in the differential diagnosis of isolated small bowel Crohn's disease when the disease is limited to a short segment of the distal small bowel, as ulcers and inflammation may result as a consequence of acid secreted from adjacent heterotopic gastric mucosa constituting the Meckel's diverticulum.

Purpose For 3 consecutive years from 2012-2014, we analyzed the causative factors for why the Jeju Island had the highest obesity prevalences of school children among the 15 provinces in Korea. Methods From our analysis of 28,026 elementary school children with obesity or normal weight in the 15 provinces, we analyzed 12 factors related to eating habits, exercise habits, lifestyle, and mental health. The differences between the obese and normal weight children were researched. Finally, Jeju was compared with Seoul, which has the lowest obesity prevalence in school age children. Statistical analysis was performed using the chi square test of PASW Statistics ver. 18.0. Results Compared to the normal weight group, the obese group had significantly higher rates of consuming soft drinks (p

Child obesity has become a significant health issue in Korea. Prevalence of obesity in school-age children in Korea has been alarmingly rising since 2008. Prevalence of obesity among infants and preschool-age children in Korea has doubled since 2008. Obese children may develop serious health complications. Before nutritional counseling is pursued, several points should be initially considered. The points are modifiable risk factors, assessment for child obesity, and principles of treatment. Motivational interviewing and a multidisciplinary team approach are key principles to consider in managing child obesity effectively in the short-term as well as long-term. Nutritional counseling begins with maintaining a daily log of food and drink intake, which could possibly be causing obesity in a child. Several effective tools for nutritional counseling in practice are the Traffic Light Diet plan, MyPlate, Food Balance Wheel, and 'Food Exchange Table'. Detailed nutritional counseling supported by a qualified dietitian is an art of medicine enabling insulin therapy and hypoglycemic agents to effectively manage diabetes mellitus in obese children.

Purpose Obese children may often present with advanced bone age. We aimed to evaluate the correlation between factors associated with childhood obesity and advanced bone age. Methods We enrolled 232 overweight or obese children. Anthropometric and laboratory data, and the degree of nonalcoholic fatty liver disease (NAFLD) were measured. We analyzed factors associated with advanced bone age by measuring the differences between bone and chronological ages. Results The normal and advanced bone age groups were comprised of 183 (78.9%) and 49 (21.1%) children, respectively. The prevalence of advanced bone age significantly increased as the percentiles of height, weight, waist circumference, and body mass index (BMI) increased. BMI z-score was higher in the advanced bone age group than in the normal bone age group (2.43±0.52 vs. 2.10±0.46; p

Purpose To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. Methods A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. Results Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. Conclusion Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

Although liver function test abnormality is frequently noted in children, there is no report about the distribution of the etiology and natural recovery time of the abnormal liver function. From March 2005 to February 2014, clinical information was retrospectively collected from 559 children who had abnormal liver function and were hospitalized or visited the outpatient clinic at the Jeju National University Hospital. The etiology of abnormal liver function was classified into groups and the natural recovery time of abnormal liver function was analyzed. The etiological groups of 559 patients included ‘nonspecific hepatitis’ in 42 (7.5%), ‘infection’ in 323 (57.8%), ‘rheumatologic and autoimmune’ in 66 (11.8%), ‘nonalcoholic fatty liver disease’ in 57 (10.2%), ‘anatomic’ in 12 (2.1%), ‘toxic’ in 13 (2.1%), ‘metabolic’ in 8 (1.4%), ‘hematologic’ in 7 (1.3%), ‘hemodynamic’ in 4 (0.7%), and ‘others’ in 27 (4.8%). Among the ‘infection’ group (57.8%), the ‘viral infection in the respiratory tract’ subgroup, which had 111 patients (19.8%), was the most common. The natural recovery time of the abnormal liver function was 27 days (median) in ‘nonspecific hepatitis’, 13 days (median) in ‘viral respiratory tract disease’, 16 days (median) in ‘viral gastroenteritis’, 42 days (median) in ‘viral febrile illness”, and 7 days (median) in “Kawasaki disease”. The information on the natural recovery time of abnormal liver function may help the physician to perform good clinical consultation for patients and their parents., Graphical Abstract

Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders., Graphical Abstract

Purpose We investigated the association of effector memory (EM) CD8+ T cell and CD4+ T cell immunity with metabolic syndrome (MS). Methods Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8+ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4+ T cell subsets. Results Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 μU/mL, p

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: (1) definition and diagnosis of overweight and obesity in children and adolescents; (2) principles of treatment of pediatric obesity; (3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; (4) pharmacotherapy; and (5) bariatric surgery.

Background We aimed to investigate mucosal immunity related to forkhead box P3 (FOXP3+) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-RORγt antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40L, and tumor necrosis factor-α. Results FOXP3+ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. RORγt+ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 (9.6 ± 1.5 vs. 12.7 ± 3.0), IL-21 (14.9 ± 1.5 vs. 26.4 ± 9.1), IL-33 (14.3 ± 0.9 vs. 19.1 ± 5.3), and IFN-γ (15.2 ± 5.9 vs. 50.2 ± 42.4) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 (119.1 ± 79.6 vs. 52.9 ± 39.1) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A (64.2 ± 17.2 vs. 28.3 ± 10.0) and IL-22 (37.5 ± 8.8 vs. 27.2 ± 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion Mucosal immunity analysis showed increased FOXP3+ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis., Graphical Abstract

DNA methylation is an epigenetic mechanism that modulates gene expression in mammalian cells including T cells. Memory T cells are heterogeneous populations. Human effector memory (EM) CD8+ T cells in peripheral blood contain two cell subsets with distinct traits that express low and high levels of the IL-7Rα. However, epigenetic mechanisms involved in defining such cellular traits are largely unknown. In this study, we use genome-wide DNA methylation and individual gene expression to show the possible role of DNA methylation in conferring distinct traits of chemotaxis and inflammatory responses in human IL-7Rαlow and IL-7Rαhigh EM CD8+ T cells. In particular, IL-7Rαlow EM CD8+ T cells had increased expression of CX3CR1 along with decreased DNA methylation in the CX3CR1 gene promoter compared with IL-7Rαhigh EM CD8+ T cells. Altering the DNA methylation status of the CX3CR1 gene promoter changed its activity and gene expression. IL-7Rαlow EM CD8+ T cells had an increased migratory capacity to the CX3CR1 ligand fractalkine compared with IL-7Rαhigh EM CD8+ T cells, suggesting an important biological outcome of the differential expression of CX3CR1. Moreover, IL-7Rαlow EM CD8+ T cells induced fractalkine expression on endothelial cells by producing IFN-γ and TNF-α, forming an autocrine amplification loop. Overall, our study shows the role of DNA methylation in generating unique cellular traits in human IL-7Rαlow and IL-7Rαhigh EM CD8+ T cells, including differential expression of CX3CR1, as well as potential biological implications of this differential expression.

Background We aimed to investigate mucosal immunity related to forkhead box P3 (FOXP3+) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-RORγt antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40L, and tumor necrosis factor-α. Results FOXP3+ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. RORγt+ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 (9.6 ± 1.5 vs. 12.7 ± 3.0), IL-21 (14.9 ± 1.5 vs. 26.4 ± 9.1), IL-33 (14.3 ± 0.9 vs. 19.1 ± 5.3), and IFN-γ (15.2 ± 5.9 vs. 50.2 ± 42.4) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 (119.1 ± 79.6 vs. 52.9 ± 39.1) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A (64.2 ± 17.2 vs. 28.3 ± 10.0) and IL-22 (37.5 ± 8.8 vs. 27.2 ± 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion Mucosal immunity analysis showed increased FOXP3+ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

Rationale: Cytokine receptors can be markers defining different T-cell subsets and considered as therapeutic targets. The association of IL-6 and IL-6 receptor α (IL-6Rα) with asthma was reported, suggesting their involvement in asthma. Objectives: To determine whether and how IL-6Rα defines a distinct effector memory (EM) CD8+ T-cell population in health and disease. Methods: EM CD8+ T cells expressing IL-6Rα (IL-6Rαhigh) were identified in human peripheral blood and analyzed for function, gene, and transcription factor expression. The relationship of these cells with asthma was determined using blood and sputum. Measurements and Main Results: A unique population of IL-6Rαhigh EM CD8+ T cells was found in peripheral blood. These cells that potently proliferated, survived, and produced high levels of the Th2-type cytokines IL-5 and IL-13 had increased levels of GATA3 and decreased levels of T-bet and Blimp-1 in comparison with other EM CD8+ T cells. In fact, GATA3 was required for IL-6Rα expression. Patients with asthma had an increased frequency of IL-6Rαhigh EM CD8+ T cells in peripheral blood compared with healthy control subjects. Also, IL-6Rαhigh EM CD8+ T cells exclusively produced IL-5 and IL-13 in response to asthma-associated respiratory syncytial virus and bacterial superantigens. Conclusions: Human IL-6Rαhigh EM CD8+ T cells is a unique cell subset that may serve as a reservoir for effector CD8+ T cells, particularly the ones producing Th2-type cytokines, and expand in asthma.

IL-15 is involved in regulating host defense and inflammation. Monocytes produce the biologically active cell surface IL-15 in response to IFN-γ. Although aging can alter the immune system, little is known about whether and how aging affects IFN-γ-mediated IL-15 production in human monocytes. We showed that monocytes of healthy older adults (age ≥ 65) had increased cell surface IL-15 expression in response to IFN-γ compared to those of healthy young adults (age ≤ 40). This finding stems in part from increased IFN-γ receptor (R)1/2 expression on monocytes in older adults, leading to enhanced STAT1 activation and interferon regulatory factor 1 synthesis with increased IL15 gene expression. Our study suggests that with aging the IFN-γ-mediated IL-15 production pathway in human monocytes is uncompromised, but rather augmented, and could be considered as a therapeutic target point to modulate host defense and inflammation in older adults.

The pathogenic hallmark of systemic lupus erythematosus is the autoimmune response against self nuclear Ags, including dsDNA. The increased expression of the proinflammatory cytokine IL-1β has been found in the cutaneous lesion and PBMCs from lupus patients, suggesting a potential involvement of this cytokine in the pathogenesis of lupus. IL-1β is produced primarily by innate immune cells such as monocytes and can promote a Th17 cell response, which is increased in lupus. IL-1β production requires cleaving pro–IL-β into IL-1β by the caspase-1–associated multiprotein complex called inflammasomes. In this study we show that self dsDNA induces IL-1β production from human monocytes dependent on serum or purified IgG containing anti–dsDNA Abs by activating the nucleotide-binding oligomerization domain–like receptor family pyrin domain–containing 3 (NLRP3) inflammasome. Reactive oxygen species (ROS) and K+ efflux were involved in this activation. Knocking down the NLRP3 or inhibiting caspase-1, ROS, and K+ efflux decreased IL-1β production. Supernatants from monocytes treated with a combination of self dsDNA and anti–dsDNA Ab+ serum promoted IL-17 production from CD4+ T cells in an IL-1β–dependent manner. These findings provide new insights in lupus pathogenesis by demonstrating that self dsDNA together with its autoantibodies induces IL-1β production from human monocytes by activating the NLRP3 inflammasome through inducing ROS synthesis and K+ efflux, leading to the increased Th17 cell response.

The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a caspase-1–containing cytosolic protein complex that is essential for processing and secretion of IL-1β. The U1-small nuclear ribonucleoprotein (U1-snRNP) that includes U1-small nuclear RNA is a highly conserved intranuclear molecular complex involved in splicing pre-mRNA. Abs against this self nuclear molecule are characteristically found in autoimmune diseases like systemic lupus erythematosus, suggesting a potential role of U1-snRNP in autoimmunity. Although endogenous DNA and microbial nucleic acids are known to activate the inflammasomes, it is unknown whether endogenous RNA-containing U1-snRNP could activate this molecular complex. In this study, we show that U1-snRNP activates the NLRP3 inflammasome in CD14+ human monocytes dependently of anti–U1-snRNP Abs, leading to IL-1β production. Reactive oxygen species and K+ efflux were responsible for this activation. Knocking down the NLRP3 or inhibiting caspase-1 or TLR7/8 pathway decreased IL-1β production from monocytes treated with U1-snRNP in the presence of anti–U1-snRNP Abs. Our findings indicate that endogenous RNA-containing U1-snRNP could be a signal that activates the NLRP3 inflammasome in autoimmune diseases like systemic lupus erythematosus where anti–U1-snRNP Abs are present.

Purpose No national survey has yet described the guidelines followed by Korean pediatricians to treat acute gastroenteritis (AGE). An online survey was performed to investigate the management of AGE followed by members of The Korean Society of Pediatric Gastroenterology, Hepatology, and Nutrition, and the results were compared between pediatric gastroenterologists (PG) and general pediatricians (GP). Methods Questionnaires were sent to pediatricians between June 2 and 4, 2018 regarding the type of hospital, indications for admission, antiemetic and antidiarrheal drugs and antibiotics prescribed, and dietary changes advised. Results Among the 400 pediatricians approached, 141 pediatricians (35.3%) responded to the survey. PG comprised 39% of the respondents and 72.7% worked at a tertiary hospital. Both PG and GP considered diarrhea or vomiting to be the primary symptom. The most common indication for hospitalization was severe dehydration (98.8%). Most pediatricians managed dehydration with intravenous fluid infusions (PG 98.2%, GP 92.9%). Antiemetics were prescribed by 87.3% of PG and 96.6% of GP. Probiotics to manage diarrhea were prescribed by 89.1% of PG and 100.0% of GP. Antibiotics were used in children with blood in diarrheal stool or high fever. Dietary changes were more commonly recommended by GP (59.3%) than by PG (27.3%) (p

To evaluate pancreatic echogenicity on transabdominal ultrasonography and the correlation of fatty pancreas with metabolic syndrome (MetS), as well as insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]).This retrospective study included 135 obese children and adolescents who underwent transabdominal ultrasonography from January 2015 to December 2015. Fatty pancreas was quantitatively analyzed using the pancreato-perihepatic fat index (PPHFI). The correlation between the PPHFI and HOMA-IR was analyzed, and multivariate logistic regression analysis was used to determine factors that were independently correlated with MetS. Receiver operating characteristic curve analysis was performed to determine the best cut-off value of the PPHFI for diagnosing MetS.The PPHFI and the HOMA-IR value were significantly higher in subjects with MetS than in those without MetS (P .0001). The PPHFI also showed an association with the HOMA-IR value (r = 0.70; P .0001). The PPHFI was an independent factor for diagnosing MetS (OR 4.36; P = .032). The best cut-off value for the PPHFI for a diagnosis of MetS was 2.34 with a sensitivity of 0.96 and specificity 0.70.These results suggest that an increased PPHFI is significantly correlated with MetS and insulin resistance, and that the PPHFI may be a useful indicator for diagnosing MetS in obese children and adolescents. The impact of the presence of fatty pancreas in obese children and adolescents must be evaluated.

We report an 8-year-old boy with Henoch-Scholein purpura (HSP) who had initially developed diffuse duodenal ulcers, accompanied by acute pancreatitis. The patient did not respond to conventional corticosleroid therapy and continued complaining severe abdominal pain and bloody stool. Even after intravenous immunoglobulin (IVIG) was administered, the patient complained persistent abdominal pain. And then we could identify acute pancreatitis combined by HSP from the patient Therefore we suggest that we Should rule out acute pancreatitis in the HSP patient with severe gastrointestinal manifestation which is refractory to medical treatment.

The paper proposes an evaluation technique for the elastic modulus of a cantilever beam by vibration analysis based on time average electronic speckle pattern interferometry (TA-ESPI) and Euler–Bernoulli equation. General approaches for the measurement of elastic modulus of a thin film are the Nano indentation test, Buldge test, Micro-tensile test, and so on. They each have strength and weakness in the preparation of the test specimen and the analysis of experimental results. ESPI is a type of laser speckle interferometry technique offering non-contact, high-resolution and whole-field measurement. The technique is a common measurement method for vibration mode visualization and surface displacement. Whole-field vibration mode shape (surface displacement distribution) at resonance frequency can be visualized by ESPI. And the maximum surface displacement distribution from ESPI can be used to find the resonance frequency for each vibration mode shape. And the elastic modules of a test material can be easily estimated from the measured resonance frequency and Euler–Bernoulli equation. The TA-ESPI vibration analysis technique can be used to find the elastic modulus of a material requiring simple preparation process and analysis.

Shearography, a type of speckle interferometry, is a powerful tool for nondestructive testing (NDT) because it is insensitive to environmental vibration disturbance and easy to detect strain concentration in an internal defect with noncontact and whole field. The shearing amount in Shearography has influence on determining defect size and source location. Thus the shearing amount must be optimally adjusted to get accurate evaluation. This paper investigates the defect size and source location according to the change of shearing amount in artificial slender defects along longitudinal direction of pipeline. Based on the investigation, a new technique is proposed for the quantitative determination of defect size and source location.

This paper proposes non-destructive ESPI technique to evaluate inside defects of semiconductor package quantitatively inspection system consists of ESPI system, thermal loading system and adrabatic chamber. The technique has high feasibility in non-destructive testing of semiconductor and gives solutions to the drawbacks in previous technique, time-consuming and the difficulty of quantitative evaluation in result, most of defects are classified in delamination, from which it is inferred to the insufficiency of adhesive strength between layers and nonhomogeneous heat spread The 90% of tested samples have a delamination defect started at the around of the chip which may be related to heat spread design.

This paper describes the speckle shearing interferometry, a non-destructive optical method, for quantitative estimation of void defect and monitoring separation defect inside of a pneumatic tire. Previous shearing interferometry has not supplied quantitative result of inside defect, due to effective factors. In the study, factors related to the details of an inside defect are classified and optimized with pipeline simulator. The size and the shape of defect can be estimated accurately to find a critical point and also is closely related with shearing direction. The technique is applied for quantitative estimation of defects inside of a pneumatic tire. The actual traveling tire is monitored to reveal the cause of separation and the starting points. And also unknown void defects on tread are inspected and the size and shape of defects are estimated which has good agreement with the result of visual inspection.