Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

There is increasing evidence demonstrating that reward-related motivational food intake is closely connected with the brain’s homeostatic system of energy balance and that this interaction might be important in the integrative control of feeding behavior. Dopamine regulates motivational behavior, including feeding behaviors, and the dopamine reward system is recognized as the most prominent system that controls appetite and motivational and emotional drives for food. It appears that the dopamine system exerts a critical role in the control of feeding behavior not only by the reward-related circuit, but also by contributing to the homeostatic circuit of food intake, suggesting that dopamine plays an integrative role across the converging circuitry of control of food intake by linking energy state-associated signals to reward-related behaviors. This review will cover and discuss up-to-date findings on the dopaminergic control of food intake by both the reward-related circuit and the homeostatic hypothalamic system.

There is increasing evidence demonstrating that reward-related motivational food intake is closely connected with the brain’s homeostatic system of energy balance and that this interaction might be important in the integrative control of feeding behavior. Dopamine regulates motivational behavior, including feeding behaviors, and the dopamine reward system is recognized as the most prominent system that controls appetite and motivational and emotional drives for food. It appears that the dopamine system exerts a critical role in the control of feeding behavior not only by the reward-related circuit, but also by contributing to the homeostatic circuit of food intake, suggesting that dopamine plays an integrative role across the converging circuitry of control of food intake by linking energy state-associated signals to reward-related behaviors. This review will cover and discuss up-to-date findings on the dopaminergic control of food intake by both the reward-related circuit and the homeostatic hypothalamic system.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND: The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. METHODS: We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. RESULTS: In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. CONCLUSION: We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors.
Amygdala ; Animals ; Arcuate Nucleus ; Brain* ; Dopamine* ; Eating* ; Feeding Behavior ; Fluorescent Antibody Technique ; Homeostasis ; Hypothalamus ; Mice ; Mice, Transgenic ; Motivation ; Obesity ; Receptor, Melanocortin, Type 4* ; Receptors, Dopamine D2* ; Reward ; Ventral Tegmental Area

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.
Adipocytes ; Adipokines ; Animals ; Body Mass Index ; Carrier Proteins ; Genes, Overlapping ; Humans ; Interleukin-6 ; Intra-Abdominal Fat ; Leukocyte Count ; Mice ; Microarray Analysis ; Models, Animal ; Obesity ; Peroxisomes ; Polymerase Chain Reaction ; PPAR gamma ; Rats ; Rats, Inbred OLETF ; Reverse Transcription ; Transcriptome*

PURPOSE: As a preliminary study on the development of a new developmental screening tool, this study examined the validity of the Korean Ages and Stages Questionnaires (K-ASQ). METHODS: The clinical sample included a total of 218 Infants and children at 30, 36, 60 months of age, who were diagnosed with developmental disorders. Age- and sex-matched normal controls were selected from a national large-scale K-ASQ database. Sensitivity, specificity, and accuracy were calculated in different age and diagnosis groups, and receiver operating characteristic (ROC) curve analysis was performed as well. In addition, concurrent validity was analyzed for the clinical sample by comparing the K-ASQ with other reference scales. RESULTS: The sensitivity, specificity, and accuracy of the K-ASQ were above fair (0.82-0.96) overall, however they varied depending on age and diagnosis groups. Specifically, the sensitivity at 60 months was relatively low (0.65). Especially, the discrimination sensitivity for the language delay group was poor at 60 months (0.42). ROC analysis showed that the overall discrimination capacity was above fair in all 5 domains [area under the curve (AUC): 0.74-0.98]. However, there were some domains and age groups with relatively poor discrimination capacity. In terms of concurrent validity, the correlations between the K-ASQ domains and reference scale subscales were statistically significant overall, but weak in some domains. CONCLUSION: The overall discrimination capacity and concurrent validity of the K-ASQ were above fair, but there were some domains, age, and diagnosis groups in which the K-ASQ was not successful in identifying potentially developmentally challenged children. These findings suggested the need for the development of a new developmental screening test tool, which is suitable for Korean infants & children.
Child* ; Diagnosis ; Discrimination (Psychology) ; Humans ; Infant* ; Language Development Disorders ; Mass Screening ; Surveys and Questionnaires* ; ROC Curve ; Sensitivity and Specificity ; Weights and Measures

To determine the role of dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) core in cocaine-induced behavioral sensitization, D2R antagonist, raclopride was bilaterally microinjected (2.5 or 5 nmol) into the NAc core of WT and D2R-/- mice and the initiation and expression phase of cocaine-mediated locomotor sensitization were analyzed. WT and D2R knockout (D2R-/-) mice received bilateral injections of either saline, or raclopride at the NAc core 30 min before each of five daily repeated injections of saline or cocaine (15 mg/kg i.p.). Following 2 weeks of withdrawal after repeated exposure to cocaine, the animals were pre-treated with an intra-accumbal injection of vehicle or raclopride before receiving a systemic cocaine challenge for the expression of sensitization. Animals which had been microinjected raclopride into NAc core displayed the enhancement of cocaine-induced behavioral response for the initiation but also for the expression of sensitization in WT as well as in D2R-/- mice, which was thus unaltered as compared to vehicle-injected control group. These results suggest that D2R in NAc core is not involved in cocaine-induced behavioral sensitization.
Animals ; Cocaine ; Dopamine ; Mice ; Microinjections ; Nucleus Accumbens ; Raclopride ; Receptors, Dopamine ; Receptors, Dopamine D2

PURPOSE: We investigated the change in serum total immunoglobulin E (IgE) and allergen-specific IgE according to allergic diseases and age. METHODS: Allergic markers of children under 18 years of age with allergic diseases for the last 5 years were collected from 12 hospitals nationwide. The total data was 9,710. Data about levels of serum total IgE and allergen-specific IgE to 15 common allergens were collected. RESULTS: In children with asthma, serum total IgE was higher in older age than in younger age until age 7 to 12 years, at which time the level was highest (paper radioimmunosorbent test, 526.7 IU/mL; UniCAP, 339.9 IU/mL). The level was lower in older age than that during younger age. This change was similar to that in children with allergic rhinitis and atopic dermatitis. The level was highest at ages 7 to 12 years in children with allergic rhinitis, and at age 10 to 12 years in children with atopic dermatitis. In children with both asthma and allergic rhinitis, as well as in children with all three diseases, the change in serum total IgE was similar to that of children with an isolated disease. The highest level in children with all three diseases was higher than that in children with an isolated disease. The analysis of allergen-specific IgE positivity showed that food allergens were dominant before the age of 2 years, and that aeroallergens such as house dust mites were dominant. CONCLUSION: Serum total IgE in Korean children with allergic diseases was higher in older age than in younger age until the ages of 7 to 12 years, and then the change in total IgE by age was the opposite.
Allergens ; Asthma ; Child ; Dermatitis, Atopic ; Hospitals, General ; Humans ; Immunoglobulin E ; Immunoglobulins ; Korea ; Pyroglyphidae ; Radioimmunosorbent Test ; Rhinitis ; Rhinitis, Allergic, Perennial

PURPOSE: This study was done to analyze the job of clinical research coordinators (CRCs). METHODS: Through the "developing a curriculum (DACUM)" workshop, the definition of CRCs' role was described and CRCs' duties and tasks were identified. Finally, the developed duties and tasks were validated for importance, difficulty, and frequency. RESULTS: A CRC is defined as the one who coordinates and performs tasks related to clinical research/trials among investigators, participants, and sponsors according to the Good Clinical Practice at institutions conducting clinical trials. Twelve duties and 78 tasks were identified on the DACUM chart which represented the importance, difficulty, and frequency of tasks represented as A, B, and C respectively. Based on determinant coefficient (DC) of the task, the highest ranked task was confirming the eligibility of participants for research (DC=8.03) and the lowest was inventory management for clinical study materials (3.95). CONCLUSION: In this study, the job of a CRC was analyzed through the DACUM process and it was found that CRCs were doing various duties and tasks. Based on these results, it is suggested that it is necessary to develop CRC education programs considering the career ladder of CRCs.
Biomedical Research ; Curriculum ; Humans ; *Job Description ; Research Personnel/*standards ; Task Performance and Analysis