Significant Shortening of Leukocyte Telomere Length in Korean Patients with Bipolar Disorder 1

Objective@#Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder.However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls. @*Methods@#We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2). @*Results@#We found significant telomere shortening in patients with BD1 (p ＜ 0.001), but not in patients with BD2.In male patients with BD1, the 30−39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19−29-year age group had significantly shortened telomeres compared to the controls (p ＜ 0.01). @*Conclusion@#Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.

Significant Shortening of Leukocyte Telomere Length in Korean Patients with Bipolar Disorder 1

Objective@#Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder.However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls. @*Methods@#We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2). @*Results@#We found significant telomere shortening in patients with BD1 (p ＜ 0.001), but not in patients with BD2.In male patients with BD1, the 30−39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19−29-year age group had significantly shortened telomeres compared to the controls (p ＜ 0.01). @*Conclusion@#Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.

Investigation of gene-gene interactions of clock genes for chronotype in a healthy Korean population

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

Investigation of gene-gene interactions of clock genes for chronotype in a healthy Korean population

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

Applying Artificial Intelligence for Diagnostic Classification of Korean Autism Spectrum Disorder

Objective@#The primary objective of this study was to predict subgroups of autism spectrum disorder (ASD) based on the Diagnostic Statistical Manual for Mental Disorders-IV Text Revision (DSM-IV-TR) by machine learning (ML). The secondary objective was to set up a ranking of Autism Diagnostic Interview-Revised (ADI-R) diagnostic algorithm items based on ML, and to confirm whether ML can sufficiently predict the diagnosis with these minimum items. @*Methods@#In the first experiment, a multiclass decision forest algorithm was applied, and the diagnostic algorithm score value of 1,269 Korean ADI-R test data was used for prediction. In the second experiment, we used 539 Korean ADI-R case data (over 48 months with verbal language) to apply mutual information to rank items used in the ADI diagnostic algorithm. @*Results@#In the first experiment, the results of predicting in the case of pervasive developmental disorder not otherwise specified as “ASD” were almost three times higher than predicting it as “No diagnosis.” In the second experiment, the top 10 ranking items of ADI-R were mainly related to the quality abnormality of communication. @*Conclusion@#In conclusion, we verified the applicability of ML in diagnosis and found that the application of artificial intelligence for rapid diagnosis or screening of ASD patients may be useful.

Higher Lactate Level and Lactate-to-Pyruvate Ratio in Autism Spectrum Disorder

Mitochondrial dysfunction is considered one of the pathophysiological mechanisms of autism spectrum disorder (ASD). However, previous studies of biomarkers associated with mitochondrial dysfunction in ASD have revealed inconsistent results. The objective of this study was to evaluate biochemical markers associated with mitochondrial dysfunction in subjects with ASD and their unaffected family members. Lactate and pyruvate levels, as well as the lactate-to-pyruvate ratio, were examined in the peripheral blood of probands with ASD (Affected Group, AG) and their unaffected family members (biological parents and unaffected siblings, Unaffected Group, UG). Lactate ≥22 mg/dl, pyruvate ≥1.4 mg/dl, and lactate-topyruvate ratio >25 were defined as abnormal. The clinical variables were compared between subjects with higher (>25) and lower (≤25) lactate-topyruvate ratios within the AG. The AG (n=59) had a significantly higher lactate and lactate-to-pyruvate ratio than the UG (n=136). The frequency of subjects with abnormally high lactate levels and lactate-to-pyruvate ratio was significantly higher in the AG (lactate 31.0% vs. 9.5%, ratio 25.9% vs. 7.3%, p<0.01). The relationship between lactate level and the repetitive behavior domain of the Autism Diagnostic Interview-Revised was statistically significant. These results suggest that biochemical markers related to mitochondrial dysfunction, especially higher lactate levels and lactateto-pyruvate ratio, might be associated with the pathophysiology of ASD. Further larger studies using unrelated individuals are needed to control for the possible effects of age and sex on chemical biomarker levels.

The pharmacology course for preclinical students using team-based learning / 한국의학교육

Purpose@#A pharmacology course in undergraduate medical education aims to enable students to cultivate the ability of applying drugs in the clinical context using basic scientific knowledge. Although team-based learning could be a useful approach, the literature on pharmacology education using team-based learning is limited. This study aims to evaluate the effectiveness of a pharmacology course using team-based learning. @*Methods@#We developed an “integrated clinical pharmacology” course for first-year medical students. All 49 students enrolled in the course. Individual and group scores were recorded for each session, and a post-course survey was conducted after the course. We compared the performance of the current class to that of a previous class based on scores in a nationwide test conducted at the end of every year. @*Results@#The reactions of the students were generally positive, with the exception of their perception of the preparatory burdens for the individual test. Throughout the team-based learning sessions, the achievement at the group level was significantly higher than at the individual level. In the nationwide test, however, when we divided students into high and low achiever groups, only the low achievers demonstrated significant improvement compared to the cohort from the previous year. @*Conclusion@#The study demonstrates that team-based learning could be an effective way of teaching pharmacology to medical students in the preclinical stage. Although most of the students were actively engaged regardless of their preparedness, low-achieving students in particular seemed to gain more benefits than high achievers regarding the acquisition of knowledge.

The Effects of a Communication Program on Incivility, Critical Thinking, and Clinical Practice Stress Experienced by Nursing Students / 한국간호교육학회지

PURPOSE: To identify the effects of a communication program on nursing students' incivility, critical thinking, and clinical practice stress. METHODS: A randomized control group pretest-posttest study was conducted. Fifty randomly selected nursing students were divided into experimental and control groups. A 160-minute communication program was applied to the experimental group and a second survey was conducted two weeks later, shortly after their clinical practice. RESULTS: There was a statistically significant difference in the incivility experienced in the clinical practice after application of the communication program, and refusal in the sub-categories of incivility was statistically significant in this group. CONCLUSION: It is necessary to foster communication skills for nursing students. Communication programs reduce incivility. Therefore, nursing educators need to recognize the importance of communication during clinical practice and consider incorporating it into their regular curricula.

Polymorphism in the Promoter Region of SEMA5A Is Associated with Sociality Traits in Korean Subjects with Autism Spectrum Disorders

In this study, we evaluated the association between autism spectrum disorders (ASDs) and 10 single-nucleotide polymorphisms (SNPs) in the 5' region of the semaphorin 5A gene (SEMA5A) for 250 Korean trios including children with ASDs. Family-based association testing and haplotype analysis revealed a statistically significant association between rs194085 and multiple sociality traits with Korean ASDs in the dominant model (p < 0.001, corrected p=0.035). This indicates that genetic variations in the 5' region of SEMA5A play a role in the genetic predisposition to sociality traits in Korean ASDs.

Polymorphisms of BDNF Gene and Autism Spectrum Disorders: Family Based Association Study with Korean Trios

OBJECTIVE: Autism spectrum disorders (ASDs) are a group of early childhood-onset neurodevelopmental disorders characterized by deficits in social interaction and language skills, and repetitive behaviors. Brain-derived neurotrophic factor (BDNF) plays a critical role in the differentiation of normal neuronal cells during embryonic and postnatal neuronal development through its neurotrophic effects. METHODS: In this study, we performed a family-based association test (FBAT) between single nucleotide polymorphisms (SNPs; rs6265, rs11030101, rs7103411, and rs7103873) or haplotypes in the BDNF gene and affection status or several quantitative traits characterized by ADI-R with151 Korean trios, including a child diagnosed as ASDs. RESULTS: While no significant association was found between SNPs or haplotypes and the ASDs disease status, a quantitative transmission disequilibrium test (QTDT) by using quantitative traits identified associations of the SNPs (rs6265 and rs11030101) with a domain score for "Restricted, Repetitive and Stereotyped patterns of behavior" (C domain), especially at the subdomain scores for "encompassing preoccupation or circumscribed pattern of interest" (C1) (rs6265A allele, dominant model, p-value=0.019; rs11030101 A allele, additive model, p-value=0.015) and "preoccupations with part of objects or non-functional elements of material" (C4) (rs11030101 A allele, additive model, p-value=0.015) within the ADI-R diagnostic algorithm. In addition, significant associations were also identified between the haplotypes and these quantitative traits (C1, p-value=0.016; C4, p-value=0.012). CONCLUSION: We conclude that BDNF gene polymorphisms have a possible role in the pathogenesis of ASDs.

Association of the Catechol-o-Methyltransferase Gene Polymorphisms with Korean Autism Spectrum Disorders

This study evaluated the family-based genetic association between autism spectrum disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios (dominant model Z = 2.598, P = 0.009, P(FDR) = 0.045). We found a statistically significant allele transmission or association in terms of the rs6269 SNP in the ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269 demonstrated significant evidence of an association with ASDs (additive model rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P(FDR) = 0.040). Thus, an association may exist between the variants of the COMT gene and the occurrence of ASDs in Koreans.

Genome-Wide Association Scan of Korean Autism Spectrum Disorders with Language Delay: A Preliminary Study

OBJECTIVE: Communication problems are a prevalent symptom of autism spectrum disorders (ASDs), which have a genetic background. Although several genome-wide studies on ASD have suggested a number of candidate genes, few studies have reported the association or linkage of specific endophenotypes to ASDs. METHODS: Forty-two Korean ASD patients who showed a language delay were enrolled in this study with their parents. We performed a genome-wide scan by using the Affymetrix SNP Array 5.0 platform to identify candidate genes responsible for language delay in ASDs. RESULTS: We detected candidate single-nucleotide polymorphisms (SNPs) in chromosome 11, rs11212733 (p-value=9.76x10(-6)) and rs7125479 (p-value=1.48x10(-4)), as a marker of language delay in ASD using the transmission disequilibrium test and multifactor dimensionality reduction test. CONCLUSION: Although our results suggest that several SNPs are associated with language delay in ASD, rs11212733 we were not able to observe any significant results after correction of multiple comparisons. This may imply that more samples may be required to identify genes associated with language delay in ASD.

The Efficacy of Urinary Albumin-to-Osmolality Ratio in Predicting 24-hour Urine Albumin Excretion in Type 2 DM Patients / 대한신장학회지

PURPOSE: Microalbuminuria is a predictive marker for early diabetic nephropathy and an independent risk factor for cardiovascular disease. Screening for the presence of microalbuminuria is one of the best ways to detect early kidney damage in patients with diabetes or other disease, and also is of great significance in prevention of cardiovascular disease. Recently spot urine albumin-to-creatinine ratio (ACR) has been proposed as a screening test for microalbuminuria. However, the creatinine level is affected by diet, drugs, age, muscle mass and race, etc. The cutoff value for ACR has generated some controversy. In this report, we evaluated the efficacy of spot urine albumin-to-osmolality ratio (AOR) in order to predict 24-hour urine albumin excretion (AER). METHODS: Seventy-three patients diagnosed as type 2 DM in DUIH were recruited. Urine was collected for 24 hours for the measurement of microalbumin and first morning urine was obatined for the measurement of ACR and AOR. We evaluated the correlation of AER and ACR or AOR. RESULTS: Correlation between spot urine AOR and 24 hour urine AER (Spearmans' rho=0.804, p<0.01) was similar to that between ACR and AER (Spearman's rho=0.872, p<0.01). Also correlation analysis revealed that AOR is closely correlated with ACR (Spearman's rho=0.939, p<0.01). We evaluate accuracy of spot urine ACR and AOR using receiver operating characteristics (ROC) curve, AUC were 0.97, 0.94, respectively. CONCLUSION: AOR correlates closely with AER. Both AOR and ACR are effective predictors of microalbuminuria. Therefore AOR is an alternative to ACR in the detection and follow-up of microalbuminuria in patients with DM.

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

BACKGROUND: Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects. METHODS: We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (DeltaHbA1c) and fasting plasma glucose (DeltaFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in DeltaHbA1c or >20% in DeltaFPG levels at 24 weeks. RESULTS: We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70+/-2.40 vs. 26.00+/-2.26, P< or =0.01) and were younger (58.83+/-11.57 years vs. 62.87+/-12.09 years, P=0.03) than the non-responder group. CONCLUSION: In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

Response: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65)

No abstract available.

No Association between Copy Number Variation of the TCRB Gene and the Risk of Autism Spectrum Disorder in the Korean Population

Although autism spectrum disorder (ASD) has been thought to have a substantial genetic background, major contributing genes have yet to be identified or successfully replicated. Immunological dysfunction has been suggested to be associated with ASD, and T cell-mediated immunity was considered important for the development of ASD. In this study, we analyzed 163 ASD subjects and 97 normal controls by genomic quantitative PCR to evaluate the association between the copy number variation of the 7q34 locus, harboring the TCRB gene, and ASDs. As a result, there was no significant difference of the frequency distribution of TCRB copy numbers between ASD cases and normal controls. TCRB gene copy numbers ranged from 0 to 5 copies, and the frequency distribution of each copy number was similar between the two groups. The proportion of the individuals with 2 copies of TCRB was 11.7% (19/163) in ASD cases and 12.1% (11/91) in the control group (p=0.68). After the effects of sex were adjusted by logistic regression, ORs for individuals with 2 copies showed no significant difference compared with the diploid copy number as reference (n=2). Although we could not see the positive association, our results will be valuable information for mining ASD-associated genes and for exploring the role of T cell immunity further in the pathogenesis of ASD.

Fitz-Hugh-Curtis syndrome is not uncommon / 대한내과학회지

Fitz-Hugh-Curtis (FHC) syndrome is hepatitis characterized by severe right upper abdominal pain associated with pelvic inflammatory disease (PID), mimicking the symptoms of acute abdomen, such as in acute cholecystitis. FHC syndrome is becoming more common with the increasing incidence of PID in Korea. We treated eight patients with FHC syndrome, who visited our hospital with right upper quadrant abdominal pain. We emphasize the importance of spiral computed tomography (CT) in the diagnosis of right upper quadrant abdominal pain in sexually active young women.

A Case of Successful Clipping of a Colonic Perforation during Diagnostic Colonoscopy / 대한소화기내시경학회지

The use of colonoscopy is important to prevent colon cancer. Despite the safety of the colonoscopy procedure, the most common complication of a colonoscopy is perforation, which occurs with a rate of approximately 0.3% during diagnostic colonoscopy and occurs with a rate of approximately 1.1% with the use of therapeutic colonoscopy. Surgery is the treatment of choice for most cases of colonic perforation. With the development of endoscopic devices and techniques, conservative treatment of colonic perforation has been reported by the use of endoscopic clipping. We report here a patient with iatrogenic perforation of the sigmoid colon that was caused by diagnostic colonoscopy. The perforation presented as pneumoretroperitoneum, which was successfully treated with endoscopic clipping.

No Association Study of SLC6A4 Polymorphisms with Korean Autism Spectrum Disorder

OBJECTIVES : The serotonin transporter gene(SLC6A4) is one of the most widely studied candidate genes in autism spectrum disorder(ASD), but there have been conflicting results from studies into the association between SLC6A4 and ASD. The aim of this study was to evaluate the association between single nucleotide polymorphisms(SNPs) in the SLC6A4 gene and ASD in the Korean population. METHODS : We selected 12 SNPs in SLC6A4 and observed the genotype of 151 Korean ASD trios. We tested the family-based association for each individual polymorphism and haplotype by using the standard TDT method in Haploview(http : /www.broad.mit.edu/mpg/haploview/). RESULTS : Through transmission-disequilibrium testing and haplotype analysis, we could not find any statistically significant transmitted allele or haplotype. In addition, a case-control association test with Korean HapMap data did not reveal any statistical significance. CONCLUSION : Although serotonin-related genes must be considered candidate genes for ASD, we suggest that common SNPs of SLC6A4 are not important markers for associations with Korean ASD.

Body Mass Index is Associated with USF1 Haplotype in Korean Premenopausal Women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m(2) and BMI <25 kg/m(2) groups in premenopausal females ( chi-square=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.