Objective Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified ...163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. Methods We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. Results We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10−14), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10−10) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10−9), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10−12) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10−5)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. Conclusions Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.
Recent reports associate rotavirus infection with neonatal seizures of distinctive white matter injury (WMI) pattern, but evidence is lacking. We examined this association prospectively and analyzed ...factors related to occurrence of seizures and WMI pattern in neonates with rotavirus infection.
We prospectively included 228 neonates (≥34 gestational weeks) who were admitted to a regional neonatal intensive care unit between February 2015 and April 2016 and underwent rotavirus antigen testing using stool samples. Patients with neonatal seizures of other etiologies were excluded.
Seventy-eight (34.2%) neonates were rotavirus-positive. Otherwise-unexplained seizures were more frequently observed among rotavirus-positive than among rotavirus-negative neonates (20.5% vs. 4.0%, p < 0.001). Rotavirus infection increased the risk of seizures (odds ratio OR, 6.19; p < 0.001), even after adjustment for confounders (OR, 4.46; p = 0.007). After stratification according to probiotic administration immediately after birth, rotavirus infection remained a significant risk factor only in patients without probiotic medication (OR, 4.83; p = 0.01 vs. OR, 2.44; p = 0.49). The WMI pattern was observed in 9 of 22 neonates with seizures, and this subgroup was characterized by rotavirus infection (100% vs. 53.8%, p = 0.004) and seizure onset on days 4–6 of life (66.7% vs. 15.0%; p = 0.02). G9P8 was the most common genotype in this subgroup but was also commonly detected in neonates without seizures.
Rotavirus infection is an independent risk factor for neonatal seizures, and associated with the WMI. Immediate administration of probiotics after birth may reduce rotavirus-associated neonatal seizures.
Helicobacter pylori infection has declined over recent decades. However, its prevalence remains high, and nearly 50% of the global population has been infected. In Korea, seroprevalence has steadily ...decreased in adults, but the status of H. pylori infection in children is unknown. The current status or trend of H. pylori infection in children is important because it can help estimate H. pylori-related diseases including gastric cancer in later life. In this review, the authors discuss the change in H. pylori infection rate among children and adolescents based on literature reviews and our research.
ABSTRACT
Infection with Helicobacter pylori leads to gastritis, peptic ulcers and gastric cancer. Moreover, when the gastric mucosa is exposed to H. pylori, gastric mucosal inflammatory cytokine ...interleukin‐8 (Il‐8) and reactive oxygen species increase. Anthocyanins have anti‐oxidative, antibacterial and anti‐inflammatory properties. However, the effect of anthocyanins in H. pylori‐infected cells is not yet clear. In this study, therefore, the effect of anthocyanins on H. pylori‐infected human gastric epithelial cells was examined. AGS cells were pretreated with anthocyanins for 24 hrs followed by H. pylori 26695 infection for up to 24 hrs. Cell viability and ROS production were examined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and 2′,7′–dichlorofluorescein diacetate assay, respectively. Western blot analyses and RT‐PCR were performed to assess gene and protein expression, respectively. IL‐8 secretion in AGS cells was measured by ELISA. It was found that anthocyanins decrease H. pylori‐induced ROS enhancement. Anthocyanins also inhibited phosphorylation of mitogen‐activated protein kinases, translocation of nuclear factor‐kappa B and Iκβα degradation. Furthermore anthocyanins inhibited H. pylori‐induced inducible nitric oxide synthases and cyclooxygenase‐2 mRNA expression and inhibited IL‐8 production by 45.8%. Based on the above findings, anthocyanins might have an anti‐inflammatory effect in H. pylori‐infected gastric epithelial cells.
This study aimed to investigate the macrophage migration inhibitory factor (MIF) and associated clinical factors in neonates. Clinical information and blood samples were obtained from 77 neonates. ...Clinical details were reviewed from medical records, and MIF was measured by enzyme-linked immunosorbent assay using blood samples acquired within a week after birth. Statistical analyses were performed between plasma MIF concentration and clinical factors. Among the 77 newborn infants, 25 were born at <34 weeks of gestation (preterm), 25 at 34 to 37 weeks (late preterm), and 27 at term gestation. The mean MIF was 9849.5 ± 7187.8 pg/mL in preterm, 5718.7 ± 4596.4 in late preterm, and 5361.1 ± 3895.7 in term infants (
P
= .016). Among 25 preterm infants born at <34 weeks of gestation, MIF was significantly higher in infants with necrotizing enterocolitis (NEC, 19,478.6 ± 8162.4 pg/mL, n = 5) than that in infants without NEC (feeding intolerance 7173.7 ± 4203.0 pg/mL, n = 12 and others 7844.9 ± 5311.2 pg/mL, n = 8,
P
= .020). Elevated plasma MIF levels in the transitional period were significantly associated with preterm birth before 34 weeks of gestation and the development of NEC.
Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of ...susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population.
Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls.
We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10, odds ratio OR = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans.
Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.
Henoch- Schönlein purpura (HSP) is the most common vasculitis of childhood. Subcutaneous edema in the extremities is a common finding of HSP, whereas lumbosacral edema is a rare presentation. We ...report a case of HSP in a six year old boy who visited the emergency department for acute - onset back pain with gait problems. An extensive radiologic workup was performed, but the patient was finally diagnosed with HSP based on knee and ankle edema with a few purpura. We described the clinical, imaging findings, and treatment of the current case and review the literature regarding this rare presentation of HSP.
Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital ...CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date.
This study aimed to investigate the presence of autoantigens in the gastric juices of children.
Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric ...endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0-5, 6-10, and 11-15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis.
There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or
infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years. Histopathological findings were significantly different among active gastritis (
=0.037) and
infiltration (
=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3-4 and molecular weights of 31-45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C.
Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.
OBJECTIVE:To report a consecutive series of neonates with seizures or apnea and displaying white matter injuries with distinctive magnetic resonance diffusion-weighted imaging (DWI) pattern, and to ...discuss the high positive rate of rotavirus infection seen in these patients.
METHODS:In a retrospective review of neonates who were admitted to a tertiary referral center with seizures or apnea, we found a distinctive pattern of white matter injury (symmetrical restricted diffusion in the periventricular white matter and white matter tracts including the corpus callosum) in 18 patients. We describe the clinical and laboratory features of these 18 neonates. Additional PCR analyses for rotaviruses and parechoviruses were performed on banked frozen samples of CSF of 4 patients and blood of 15 patients.
RESULTS:All 18 patients were born at term and healthy until symptoms occurred 4–7 days after birth. No history of asphyxia was observed. Only 1 patient presented with fever, and no patient showed a rash. All patients except 1 (94.4%) were rotavirus-positive in stool samples. However, neither rotaviruses nor enteroviruses/parechoviruses were detected in the CSF and blood. Tissue loss was observed in 5 of 8 subjects on repeat MRI scans.
CONCLUSIONS:Neonates with this distinctive DWI pattern had a high positive rate of rotavirus infection, without evidence of other pathogens, and were characterized as term newborns with neurologic symptoms arising approximately the fifth day after birth. Although the specificity of this pattern is unclear, rotavirus testing should be considered for neonates presenting with this DWI pattern.
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