Objective: Tacrolimus intrapatient variability (Tac IPV) has been considered a marker for post-graft risk. We investigated pre-transplant psychometric testing to predict Tac IPV after living kidney transplantation. Methods: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) examined during pre-transplant evaluation by 102 recipients were analyzed. Subjects were divided into two groups, low IPV (L-IPV) and high IPV (H-IPV), by cutoffs of Tac IPV: median of 24 and value of 30. T-scores of MMPI-2 scales were used to analyze difference between L-IPV and H-IPV using independent t-tests. Stepwise multiple logistic regression was used to test whether MMPI-2 scales affected Tac IPV. Confusion matrix of logistic regression was used to explain statistical power. Cutoff values of significant scales for H-IPV were analyzed by constructing receiver operating characteristic curves. Results: Hysteria (Hy) and depression (D) scale scores and Tac IPV were associated in IPV 24 (odds ratio [OR]: 1.08, p<0.01 for Hy; OR: 0.93, p<0.01 for D) and IPV 30 models (OR: 1.09, p<0.01 for Hy; OR: 0.92, p<0.01 for D). Paranoia (Pa) scale scores were associated with Tac IPV in IPV 24 model (OR=1.10, p<0.01) and were significantly higher in H-IPV 24 (p<0.01). F1 scores of confusion matrix in IPV 24 and 30 models were 0.70 and 0.71, respectively. Cutoffs of Hy, D, and Pa scales were 51, 57, and 47, respectively. Conclusion MMPI-2 profile is suggested as a predictor for high Tac IPV after living kidney transplantation.

Background: Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods: In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results: Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Objective: Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. Materials and Methods: Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. Results: Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. Conclusion CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Objective: Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. Materials and Methods: Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. Results: Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. Conclusion CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Indoor animal husbandry environments are inevitably contaminated with endotoxins. Endotoxin exposure is associated with various inflammatory illnesses in animals. This cross-sectional study evaluated the relationship between the degree of endotoxin exposure and the cellular and humoral immune profiles of fattening pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes were determined. Peripheral-blood mononuclear cells were stimulated in vitro with concanavalin A for 48 h, and cytokines released into culture supernatants were measured. The barns in which the pigs lived were assessed for endotoxin levels in the total and respirable dust by using the limulus amebocyte lysate kinetic QCL method. Low and high endotoxin exposures were defined as ≤ 30 and > 30 EU/m³, respectively. Compared to pigs with low endotoxin exposure (n = 19), highly exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNγ) and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis factor-alpha (TNFα) production. The IL-4, IFNγ, and TNFα levels significantly correlated with endotoxin level and/or pig age. Constant exposure of pigs to high levels of airborne endotoxins can lead to aberrant immune profiles.
Agriculture ; Animal Husbandry ; Animals ; Blood Cell Count ; Concanavalin A ; Cross-Sectional Studies ; Cytokines ; Dust ; Endotoxins ; Horseshoe Crabs ; Housing ; Immunity, Cellular ; Immunoglobulin A ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; In Vitro Techniques ; Interferon-gamma ; Interleukin-4 ; Interleukins ; Jugular Veins ; Korea ; Lymphocytes ; Methods ; Neutrophils ; Plasma ; Swine ; Tumor Necrosis Factor-alpha

OBJECTIVES: We assessed the availability of Aberrant Behavior Checklist (ABC) for the evaluation of the pharmacological effect in autistic disorder. METHODS: A retrospective review of the medical records of 27 children with autistic disorder, who visited the department of child and adolescent psychiatry of Kyungpook National University Hospital, from October 2011 to February 2013, was conducted. After treatment with risperidone, changes in the severity and improvement of symptoms were measured using ABC at the baseline, 2nd visit and 3rd visit, respectively. RESULTS: The mean daily dose of risperidone increased from 0.66+/-0.27mg (baseline, initial dose) to 1.02+/-0.50mg, 2nd visit, and 1.19+/-0.50mg, 3rd visit. According to ABC, irritability, lethargy, hyperactivity, and inappropriate speech subscale scores decreased significantly from the baseline to 2nd visit. Irritability and Hyperactivity subscale scores decreased significantly from the 2nd to 3rd visit. All subscales and total scores of ABC decreased significantly from the baseline to 3rd visit. CONCLUSION: The results of this study suggest that ABC can be used as an efficient tool to measure the symptoms of autistic disorder and to evaluate the medication effect on continuous treatment.
Adolescent ; Adolescent Psychiatry ; Autistic Disorder* ; Checklist* ; Child* ; Humans ; Lethargy ; Medical Records ; Retrospective Studies ; Risperidone

OBJECTIVE: The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of dopamine receptor D2 (DRD2) are associated with schizophrenia in Korean population. METHODS: Four SNPs (rs4648317, rs7131056, rs4936270, and rs1076562) of DRD2 were selected and genotyped by direct sequencing in 197 schizophrenia patients and 370 control subjects. SNPAnalyzer, SNPStats, and Haploview version 4.2 programs were performed to analyze the genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were used to evaluate the odds ratios (ORs), 95% confidence intervals (CIs), and p values. For multiple testing, p values (pc) were re-evaluated by Bonferroni's correction. RESULTS: The genotype frequency of DRD2 rs4936270 SNP was associated with the development of schizophrenia (p=0.0007, OR=1.71, 95% CI=1.16-2.52 in the codominant1 model; p=0.011, OR=1.63, 95% CI=1.12-2.37 in the dominant model; p=0.035, OR=1.41, 95% CI=1.03-1.95 in the log-additive model). The allele frequency of rs4936270 was also associated with the development of schizophrenia (p=0.024, OR=1.45, 95% CI=1.05-1.98). After Bonferroni's correction, the genotype distribution of rs4936270 was still related to the development of schizophrenia (pc=0.0028 in the codominant1 model; pc=0.044 in the dominant model). A linkage disequilibrium block consisted of rs4648317, rs7131056, and rs4936270. The CAT haplotype frequency was different between schizophrenia and controls (p=0.039). CONCLUSION: These results suggest that DRD2 SNPs may be associated with the development of schizophrenia in Korean population.
Animals ; Cats ; Dopamine ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Logistic Models ; Odds Ratio ; Polymorphism, Single Nucleotide ; Receptors, Dopamine ; Schizophrenia

Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. To examine the gene expression profile in calcium-induced keratinocyte differentiation, we constructed a normalized cDNA library using mRNA isolated from these calcium-treated keratinocytes. After sequencing about 10,000 clones, we were able to obtain 4,104 independent genes. They consisted of 3,699 annotated genes and 405 expressed sequence tags (ESTs). Some were the genes involved in constituting epidermal structures and others were unknown genes that are probably associated with keratinocytes. In particular, we were able to identify genes located at the chromosome 1q21, the locus for the epidermal differentiation complex, and 19q13.1, another probable locus for epidermal differentiation-related gene clusters. One EST located at the chromosome 19q13.1 showed increased expression by calcium treatment, suggesting a novel candidate gene relevant to keratinocyte differentiation. These results demonstrate the complexity of the transcriptional profile of keratinocytes, providing important clues on which to base further investigations of the molecular events underlying keratinocyte differentiation.
Calcium/*metabolism ; Cells, Cultured ; Chromosome Mapping ; Chromosomes, Human ; Expressed Sequence Tags ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Library ; Humans ; Keratinocytes/cytology/*physiology ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis

Evidences has been accumulated the difference of cardiovascular phenotypes in autistic spectrum disorder (ASD). To determine the genetic association between fibrinogen beta chain (FGB) gene and ASD in Korean population, we genotyped single nucleotide polymorphism (SNP) (rs4220, Arg478Lys, exon 8) in the FGB gene by using direct sequencing. Among nonsynonymous SNPs in the coding region of FGB, only one SNP's heterozygosity (rs4220) is more than 0.05. Therefore, we analyzed the association between rs4220 and ASD. Three hundred six control and 196 ASD subjects were evaluated. For the analysis of genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was also used. The result showed that a SNP (rs4220) in the FGB gene was not significantly difference between ASD and controls in three alternative models. This result suggests that the FGB gene may have no relation to the development of ASD.
Clinical Coding ; Exons ; Fibrinogen ; Logistic Models ; Phenotype ; Polymorphism, Single Nucleotide

OBJECTIVES: Recently, Korean psychiatrists have noticed the complaints from probands and family members that private health insurance companies do not pay for most psychiatric disorders. Furthermore, probands cannot even apply for insurance because of their medical record of psychiatric disorders. Authors investigated and reviewed contracts of Korean private insurance companies to find reasons for banning psychiatric disorders from insurance policies. METHODS: Authors reviewed more than 800 contracts from 48 insurance companies. RESULTS: Among all the psychiatric diagnoses, few of them-dementia and some other organic mental disorders-are guaranteed to be paid from insurance companies. Less then 10 contracts say they pay for psychiatric illnesses. Most insurance companies have contracts prohibiting F codes ; however, there are not enough reasons in these contracts. CONCLUSIONS: In the private health insurance system, psychiatric illnesses have almost no rooms. It is very urgent to add space for patients with psychiatric illnesses and psychiatrists in the insurance policies.
Diagnosis ; Humans ; Insurance* ; Insurance, Health ; Korea* ; Medical Records ; Psychiatry