Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Background and aims: Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Methods: Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. Results: We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). Conclusions: The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

Quality and staling characteristics of white bread fortified with lysozyme-hydrolyzed mealworm powder (Tenebrio molitor L.).

Edible insects have a low environmental impact but are rich in nutrients and have been promoted as alternative protein sources. However, adding insect flour to bread negatively affects the overall quality, especially loaf volume and textural properties. Furthermore, relevant studies on chitin are limited. Therefore, this study examined chitin hydrolysis using lysozymes to enhance the quality characteristics in defatted mealworm (Tenebrio molitor L.) powder (DF-M)-supplemented bread. The chitin hydrolysis degree by lysozymes was evaluated using the 3,5-dinitrosalicylic acid assay and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The amount of chitin oligomers increased with time, and no significant difference in the hydrolysis efficiency between water and 400 mM acetate buffer was observed. Enzymatic hydrolysis improved the DF-M water- and oil-binding and antioxidant capacities. In addition, chitin hydrolysis increased the volume and softened the texture of white bread. In particular, bread supplemented with DF-M hydrolyzed for 4 h at 10 % had the highest moisture content among the mealworm-added bread groups during storage for 5 days. Moreover, sensory evaluation showed a positive effect of chitin hydrolysis on acceptability. Our findings indicate that chitin hydrolysis can improve the quality of bread containing insect additives. In conclusion, this study provides novel insights into producing high-quality and functional bakery products from edible insects by the enzymatic hydrolysis of edible insect powders and could expand the applications of edible insects as food ingredients.

Assessment of DNA extraction methods for human gut mycobiome analysis.

The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24TM 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.

Ulcerative Colitis Diagnosed through Evaluation of Underlying Diseases in a Pyoderma Gangrenosum Adolescent without Gastrointestinal Symptoms.

Pyoderma gangrenosum (PG) is a rare, non-infectious, neutrophilic dermatosis characterized by painful ulcers with indistinct borders and peripheral erythema. The diagnosis of PG requires the exclusion of other causes of similar appearing skin manifestations, including vasculitis and infections. The pathogenesis of PG is not clear; however, dysregulation of the immune system has been suggested in previous studies. More than half of the PG patients have underlying diseases; the most common being inflammatory bowel disease (IBD). The progression of PG in IBD patients is seen after the onset of IBD, usually during its exacerbation. On the other hand, PG may follow a course independent of the intestinal disease. We present a case of an 18-year-old young male with PG that presented before being diagnosed with ulcerative colitis as an associated condition. He had a painful ulcerative lesion on his right shin with no previous gastrointestinal symptoms. This case suggests that investigating for underlying disorders is essential in PG patients despite the lack of symptoms other than the skin lesions.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

An abrupt shift in gross primary productivity over Eastern China-Mongolia and its inter-model diversity in land surface models.

The terrestrial ecosystem in East Asia mainly consists of semi-arid regions that are sensitive to climate change. Therefore, gross primary productivity (GPP) in East Asia could be highly variable and vulnerable to climate change, which can significantly affect the local carbon budget. Here, we examine the spatial and temporal characteristics of GPP variability in East Asia and its relationship with climate factors over the last three decades. We detect an abrupt decrease in GPP over Eastern China-Mongolia region around the year 2000. This is attributed to an abrupt decrease in precipitation associated with the phase shift of the Pacific decadal oscillation (PDO). We also evaluate the reproducibility of offline land surface models to simulate these abrupt changes. Of the twelve models, eight were able to simulate this abrupt response, while the others failed due to the combination of an exaggerated CO2 fertilization effect and an underrated climate impact. For accurate prediction, it is necessary to improve the sensitivity of the GPP to changes in CO2 concentrations and the climate system.

Oral Porphyromonas gingivalis infection affects intestinal microbiota and promotes atherosclerosis.

AIM: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. MATERIALS AND METHODS: ApoE-/- mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. RESULTS: En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. CONCLUSIONS: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.

Contrast-Enhanced Ultrasonography for the Evaluation of Crohn's Disease in Pediatric Patients.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn's disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn's disease activity in children with endoscopy as the reference standard. METHOD: In this prospective study, 30 pediatric patients with Crohn's disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021. The simple endoscopic score for Crohn's disease, pediatric Crohn's disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. RESULTS: CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn's disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn's disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). CONCLUSION: CEUS can be a safe and specific diagnostic modality for Crohn's disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn's disease.

Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria.

The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.

Pre- and Immediate Post-Kasai Portoenterostomy Shear Wave Elastography for Predicting Hepatic Fibrosis and Native Liver Outcomes in Patients With Biliary Atresia.

OBJECTIVE: To evaluate the feasibility of ultrasound shear wave elastography (SWE) for predicting hepatic fibrosis and native liver outcomes in patients with biliary atresia. MATERIALS AND METHODS: This prospective study included 33 consecutive patients with biliary atresia (median age, 8 weeks [interquartile range, 6-10 weeks]; male:female ratio, 15:18) from Severance Children's Hospital between May 2019 and February 2022. Preoperative (within 1 week from surgery) and immediate postoperative (on postoperative days [PODs] 3, 5, and 7) ultrasonographic findings were obtained and analyzed, including the SWE of the liver and spleen. Hepatic fibrosis, according to the METAVIR score at the time of Kasai portoenterostomy and native liver outcomes during postsurgical follow-up, were compared and correlated with imaging and laboratory findings. Poor outcomes were defined as intractable cholangitis or liver transplantation. The diagnostic performance of SWE in predicting METAVIR F3-F4 and poor hepatic outcomes was analyzed using receiver operating characteristic (ROC) analyses. RESULTS: All patients were analyzed without exclusion. Perioperative advanced hepatic fibrosis (F3-F4) was associated with older age and higher preoperative direct bilirubin and SWE values in the liver and spleen. Preoperative liver SWE showed a ROC area of 0.806 and 63.6% (7/11) sensitivity and 86.4% (19/22) specificity at a cutoff of 17.5 kPa for diagnosing F3-F4. The poor outcome group included five patients with intractable cholangitis and three undergoing liver transplantation who showed high postoperative liver SWE values. Liver SWE on PODs 3-7 showed ROC areas of 0.783-0.891 for predicting poor outcomes, and a cutoff value of 10.3 kPa for SWE on POD 3 had 100% (8/8) sensitivity and 73.9% (17/23) specificity. CONCLUSION: Preoperative liver SWE can predict advanced hepatic fibrosis, and immediate postoperative liver SWE can predict poor native liver outcomes in patients with biliary atresia.

Advancing understanding of land-atmosphere interactions by breaking discipline and scale barriers.

Vegetation and atmosphere processes are coupled through a myriad of interactions linking plant transpiration, carbon dioxide assimilation, turbulent transport of moisture, heat and atmospheric constituents, aerosol formation, moist convection, and precipitation. Advances in our understanding are hampered by discipline barriers and challenges in understanding the role of small spatiotemporal scales. In this perspective, we propose to study the atmosphere-ecosystem interaction as a continuum by integrating leaf to regional scales (multiscale) and integrating biochemical and physical processes (multiprocesses). The challenges ahead are (1) How do clouds and canopies affect the transferring and in-canopy penetration of radiation, thereby impacting photosynthesis and biogenic chemical transformations? (2) How is the radiative energy spatially distributed and converted into turbulent fluxes of heat, moisture, carbon, and reactive compounds? (3) How do local (leaf-canopy-clouds, 1 m to kilometers) biochemical and physical processes interact with regional meteorology and atmospheric composition (kilometers to 100 km)? (4) How can we integrate the feedbacks between cloud radiative effects and plant physiology to reduce uncertainties in our climate projections driven by regional warming and enhanced carbon dioxide levels? Our methodology integrates fine-scale explicit simulations with new observational techniques to determine the role of unresolved small-scale spatiotemporal processes in weather and climate models.

Effectiveness of High-Volume Therapeutic Plasma Exchange for Acute and Acute-on-Chronic Liver Failure in Korean Pediatric Patients.

Purpose: Liver transplantation (LT) is the only curative treatment for acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In high-volume therapeutic plasma exchange (HV-TPE), extracorporeal liver support filters accumulate toxins and improve the coagulation factor by replacing them. In this study, we aimed to evaluate the effectiveness of HV-TPE in pediatric patients with ALF and ACLF. Methods: We reviewed the records of children waiting for LT at Severance Hospital who underwent HV-TPE between 2017 and 2021. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin (TB and DB), gamma-glutamyl transferase (GGT), ammonia, and coagulation parameter-international normalized ratio (INR) were all measured before and after HV-TPE to analyze the liver function. The statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Co., Armonk, NY, USA). Results: Nine patients underwent HV-TPE with standard medical therapy while waiting for LT. One had neonatal hemochromatosis, four had biliary atresia, and the other four had ALF of unknown etiology. Significant decreases in AST, ALT, TB, DB, GGT, and INR were noted after performing HV-TPE (930.38-331.75 IU/L, 282.62-63.00 IU/L, 11.75-5.59 mg/dL, 8.10-3.66 mg/dL, 205.62-51.75 IU/L, and 3.57-1.50, respectively, p<0.05). All patients underwent LT, and two expired due to acute complications. Conclusion: HV-TPE could remove accumulated toxins and improve coagulation. Therefore, we conclude that HV-TPE can be regarded as a representative bridging therapy before LT.

Loranthus tanakae Franch. & Sav. Suppresses Inflammatory Response in Cigarette Smoke Condensate Exposed Bronchial Epithelial Cells and Mice.

Loranthus tanakae Franch. & Sav. found in China, Japan, and Korea is traditionally used for managing arthritis and respiratory diseases. In this study, we analyzed the components of L. tanakae 70% ethanol extract (LTE) and investigated the therapeutic effects of LTE on pulmonary inflammation using cells exposed to cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in vitro and in vivo in mice and performed a network analysis between components and genes based on a public database. We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE, which induced a significant reduction in inflammatory mediators including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and inflammatory cells in CSC exposed H292 cells and in mice, accompanied by a reduction in inflammatory cell infiltration into lung tissue. In addition, LTE increased translocation into the nuclei of nuclear factor erythroid-2-related factor 2 (Nrf2). By contrast, the activation of nuclear factor (NF)-κB, induced by CSC exposure, decreased after LTE application. These results were consistent with the network pharmacological analysis. In conclusion, LTE effectively attenuated pulmonary inflammation caused by CSC+LPS exposure, which was closely involved in the enhancement of Nrf2 expression and suppression of NF-κB activation. Therefore, LTE may be a potential treatment option for pulmonary inflammatory diseases including chronic obstructive pulmonary disease (COPD).

Comparison between Pediatric Crohn's Disease and Ulcerative Colitis at Diagnosis in Korea: Results from a Multicenter, Registry-Based, Inception Cohort Study.

Background/Aims: We aimed to compare the differences in pediatric Crohn's disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. Methods: This was a multicenter, registry-based, inception cohort study conducted at five centers in Korea between 2013 and 2017. Baseline demographics, clinical characteristics, and results from laboratory, endoscopic, radiologic examinations were compared between pediatric CD and UC patients who were <19 years old at diagnosis. Results: A total 307 patients were included (227 CD [73.9%] and 80 UC [26.1%]). The male to female ratio was 2.49:1 for CD, and 1.49:1 for UC (p=0.019). Median age at diagnosis was 14.4 years (interquartile range, 12.4 to 16.2) for CD, and 14.4 years (interquartile range, 11.7 to 16.5) for UC (p=0.962). Hematochezia was the only dominant symptom in UC patients compared to CD patients (86.2% vs 30.8%, p<0.001). White blood cell counts, platelet counts, erythrocyte sedimentation rate, and C-reactive protein levels were significantly higher, and serum albumin level was significantly lower in CD patients than in UC patient. Anti-Saccharomyces cerevisiae antibody was positive in 44.5% and 16.2% of CD and UC patients, respectively (p<0.001), and antineutrophil cytoplasmic antibody was positive in 15.0% and 58.8% of CD and UC patients, respectively (p<0.001). Terminal ileal involvement was prominent in CD, while rectal involvement was more prominent in UC. Small bowel involvement and perianal perforating diseases were also more prominent in CD. Conclusions: This is the first a multicenter study in Korea to compare the differences between pediatric CD and UC at diagnosis in Korea. A large-scale, national study is expected to better clarify these findings in the future.

Exploration of Potential Gut Microbiota-Derived Biomarkers to Predict the Success of Fecal Microbiota Transplantation in Ulcerative Colitis: A Prospective Cohort in Korea.

Background/Aims: Although fecal microbiota transplantation (FMT) has been proven as one of the promising treatments for patients with ulcerative colitis (UC), potential prognostic markers regarding the clinical outcomes of FMT remain elusive. Methods: We collected fecal samples of 10 participants undergoing FMT to treat UC and those from the corresponding donors. We categorized them into two groups: responders and nonresponders. Sequencing of the bacterial 16S rRNA gene was conducted on the samples to explore bacterial composition. Results: Analyzing the gut microbiota of patients who showed different outcomes in FMT presented a distinct microbial niche. Source tracking analysis showed the nonresponder group had a higher rate of preservation of donor microbiota, underscoring that engraftment degrees are not one of the major drivers for the success of FMT. At the phylum level, Bacteroidetes bacteria were significantly depleted (p<0.003), and three genera, including Enterococcus, Rothia, and Pediococcus, were enriched in the responder group before FMT (p=0.003, p=0.025, and p=0.048, respectively). Furthermore, we applied a machine learning algorithm to build a prediction model that might allow the prediction of FMT outcomes, which yielded an area under the receiver operating characteristic (ROC) curve of 0.844. Notably, the microbiota-based model was much better at predicting outcomes than the clinical features model (area under the ROC curve=0.531). Conclusions: This study is the first to suggest the significance of indigenous microbiota of recipients as a critical factor. The result highlights that bacterial composition should be evaluated before FMT to select suitable patients and achieve better efficiency.

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn's Disease in Children.

PURPOSE: To identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn's disease (CD) in children. MATERIALS AND METHODS: In this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC). RESULTS: In total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/dL), lower albumin (≤4 g/dL), and higher platelet (>320×103/µL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778-2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891-0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD. CONCLUSION: Multisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.

Gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways. METHODS: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers. RESULTS: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as PHC-like and P patients, respectively. Stools of PHC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in PHC-like patients. CONCLUSIONS: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.

Significance of Follow-Up Ultrasonography 24 Hours Post-Reduction in Detecting Intussusception Recurrence.

PURPOSE: The objective of this study was to identify the significance of 24-hour post-reduction ultrasonography (US) in pediatric patients with intussusception. METHODS: A total of 229 patients with intussusception who were treated with saline reduction at Severance Children's Hospital between January 2014 and September 2020 were retrospectively reviewed. The 229 patients with successful saline reduction were divided into two groups: a recurrence at 24 hours group (R, n=41) and a non-recurrence group (NR, n=188). The full patient sample was divided into two groups: follow-up US (FU) or no follow-up US (NFU); the recurrence group was divided into follow-up (R-FU) and non-follow-up (R-NFU) subgroups, and stratified analyses were performed. RESULTS: There were no significant differences in age, sex, laboratory findings, symptoms, and sonographic findings between the NR and R groups. In the R group, 24 patients underwent follow-up US, and 17 patients did not. Specific sonographic findings were statistically significant in the R-FU group compared to the R-NFU group (p=0.002). The R-FU group had fewer admissions (p=0.012) and longer mean hospitalization times (p<0.001) than the R-NFU group. The NFU group had a 12.2% recurrence rate, while the R-FU group recurrence rate was 25.8% (p=0.0099), suggesting that the omission of some recurrent events and follow-up US was a significant variable in the recurrence of intussusception. The median time to recurrence was 21 hours which supports the 24-hour follow-up protocol. CONCLUSION: Twenty-four-hour follow-up US was shown to be valuable for detecting early recurrence of intussusception.

Evaluation of 28-day repeated oral dose toxicity of aluminum chloride in rats.

The present study investigated the potential adverse effects of aluminum chloride (AlCl3) following a 4-week repeated oral administration in Sprague-Dawley rats. The test article was administered once daily by gavage to male and female rats at dose levels of 0, 100, 300, and 900 mg/kg/day for 4 weeks. After administration of AlCl3 at 900 mg/kg/day, treatment-related systemic toxicity manifested as significant increases in salivation incidence, neutrophil percentage, reticulocytes, serum triglyceride, adrenal gland and liver weights, and single-hepatocyte necrosis, as well as significant decreases in body weight gain, food intake, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), lymphocyte percentage, serum total protein and albumin, and thymus weight in male rats; and significant increases in salivation incidence, serum triglyceride, and liver weight, as well as a significant decrease in lymphocyte percentage in female rats. At 300 mg/kg/day, a significant decrease in MCHC was found in male rats, but not in female rats. However, this finding was not toxicologically significant because the reduction was minimal and was not accompanied by changes in any other parameters. No treatment-related effects were observed in the 100 mg/kg/day group of both genders. Under the experimental conditions of this study, the target organs of AlCl3 were determined to be the blood, liver, and thymus in rats. The no-observed-adverse-effect level was found to be 300 mg/kg/day in rats of both genders.

Subchronic Toxicity Evaluation of Aluminum Oxide Nanoparticles in Rats Following 28-Day Repeated Oral Administration.

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague-Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.