Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

Medical students’ perspectives on recommencing clinical rotations during coronavirus disease 2019 at one institution in South Korea / 한국의학교육

Purpose@#Clinical rotations of medical students across the world have inevitably been affected due to the coronavirus disease 2019 (COVID-19) pandemic. The aims of this study were to explore medical students’ perception on the school’s response and management of clinical rotation during the COVID-19 pandemic and on how it had affected the quality of their education. @*Methods@#An online questionnaire was distributed to third year medical students at one institution whose clinical rotations re-started during the pandemic. The questions asked about the students’ satisfaction with the school’s policy and feelings of safety, and the impact of COVID-19 on clinical learning. @*Results@#The students’ perception on the school’s response to the pandemic was mixed. Re-commencement of the clinical rotations and procurement of personal protective equipment was positive but a third of students still felt unsafe. The decreased number of hospital patients did not seem to have impacted their overall clinical education with praise on the role of the supervising physicians. Seventy-six-point seven percent of students conferred the positive educational opportunities on medical professionalism presented to them only as the clinical rotation during the ongoing pandemic. @*Conclusion@#Our observations on the re-commencement of clerkship during this pandemic may help equip medical institutions on future public health crisis.

Correction to: Endogenous Stem Cells in Homeostasis and Aging

In the previous version of this article, two important references [47-2, 173] were missing. The authors would like to make corrections in the original version of the article.

Endogenous Stem Cells in Homeostasis and Aging

In almost all human tissues and organs, adult stem cells or tissue stem cells are present in a unique location, the so-called stem cell niche or its equivalent, continuously replenishing functional differentiated cells. Those endogenous stem cells can be expanded for cell therapeutics using ex vivo cell culture or recalled for tissue repair in situ through cell trafficking and homing. In the aging process, inefficiency in the endogenous stem cell-mediated healing mechanism can emerge from a variety of impairments that accumulate in the processes of stem cell self-renewal, function, differentiation capacity, and trafficking through cell autonomous intrinsic pathways (such as epigenetic alterations) or systemic extrinsic pathways. This review examines the homeostasis of endogenous stem cells, particularly bone marrow stem cells, and their dysregulation in disease and aging and discusses possible intervention strategies. Several systemic pro-aging and rejuvenating factors, recognized in heterochronic parabiosis or premature aging progeroid animal models, are reviewed as possible anti-aging pharmaceutical targets from the perspective of a healthy environment for endogenous stem cells. A variety of epigenetic modifications and chromosome architectures are reviewed as an intrinsic cellular pathway for aging and senescence. A gradual increase in inflammatory burden during aging is also reviewed. Finally, the tissue repair and anti-aging effects of Substance-P, a peptide stimulating stem cell trafficking from the bone marrow and modifying the inflammatory response, are discussed as a future anti-aging target.

A genome-wide association study of the association between single nucleotide polymorphisms and brachial-ankle pulse wave velocity in healthy Koreans

PURPOSE: Pulse wave velocity (PWV) is an indicator of arterial stiffness, and is considered a marker of vascular damage. However, a genome-wide association study analyzing single nucleotide polymorphisms (SNPs) associated with brachial-ankle PWV (baPWV) has not been conducted in healthy populations. We performed this study to identify SNPs associated with baPWV in healthy populations in Korea. MATERIALS AND METHODS: Genomic SNPs data for 2,407 individuals from three sites were analyzed as part of the Korean Genomic Epidemiologic Study. Without replication samples, we performed multivariable analysis as a post hoc analysis to verify the findings in site adjusted analysis. Healthy subjects aged between 40 and 70 years without self-reported history or diagnosis of hypertension, diabetes, hyperlipidemia, heart disease, cerebrovascular disease and cancer were included. We excluded subjects with a creatinine level >1.4 mg/dL (men) and 1.2 mg/dL (women). RESULTS: In the site-adjusted association analysis, significant associations (P<5×10⁻⁸) with baPWV were detected for only 5 SNPs with low minor allele frequency. In multivariable analysis adjusted by age, sex, height, body mass index, mean arterial pressure, site, smoking, alcohol, and exercise, 11 SNPs were found to be associated (P<5×10⁻⁸) with baPWV. The 5 SNPs (P<5×10⁻⁸) linked to three genes (OPCML, PRR35 and RAB40C) were common between site-adjusted analysis and multivariable analysis. However, meta-analysis of the result from three sites for the 11 SNPs showed no significant associations. CONCLUSION: Using the recent standard for genome-wide association study, we did not find any evidence of significant association signals with baPWV.

Effects of a Smart Phone Individualized Distraction Intervention on Anxiety in Pre-Op Pediatric Patients

PURPOSE: The purpose of this study was to identify whether individualized distraction intervention using a smart phone affected pre-op anxiety of children. METHODS: This was a nonequivalent control group pre-post test quasi-experimental design. The participants were 30 children in the experimental group and 30 in the control group. In experimental group, a smart phone individualized distraction intervention was given to children from the reception area to the operation room. RESULTS: For heart rate, there were no statistically significant differences between the experimental group and control group. In the behavioral anxiety response, there were statistically significant differences between the experimental group and control group (t=-3.11, p=.003). CONCLUSION: The finding suggest that, for pre-op children, the individualized distraction intervention using a smart phone had some significance as a nursing intervention having a positive impact. Such interventions can help pediatric nurses to relieve pre-op anxiety and improve health of children in their care.

The Effect of Videotaping Students' Interviews with Patients for Interview Skill Education / 가정의학회지

BACKGROUND: The importance of communication between patients and physicians has been proven in many previous studies. The authors analyzed the effect of interview skill education through videotapes which recorded students' interviews with real patients in the outpatient department of family medicine. METHODS: This study was conducted with all students who chose the elective course of family medicine and one randomly selected student every week from an 'infectious internal medicine' class at Dongguk University Ilsan Hospital during the period from December 2008 to March 2011. All students performed a preliminary examination of a new patient at the outpatient department of family medicine. All consultations were videotaped. Feedback to the student was given on the same day by viewing the videotape together. After feedback, all students performed another preliminary examination of one new patient at the department of family medicine the same week. Three family medicine residents scored all videotapes using 10-item interview skill checklists. Many parts of the checklists were modified using the Arizona Clinical Interview Rating Scales. RESULTS: Thirty-three students participated. Of 10 items, nine showed increased scores after feedback. There was a significant change in four items after feedback: 'type of question' (before 2.36 +/- 0.60, after 2.73 +/- 0.72), 'timeline' (before 2.82 +/- 0.68, after 3.18 +/- 0.73), 'positive verbal reinforcement' (before 2.24 +/- 0.56, after 2.61 +/- 0.90), and the total score (before 21.70 +/- 2.62, after 23.39 +/- 3.13) (P < 0.05). CONCLUSION: Giving feedback to medical school students on medical interview skills using videotapes of students' preliminary consultations with real patients in outpatient settings, was effective in improving the interview areas of 'type of question,' 'timeline,' 'positive verbal reinforcement,' and the total interview scores.

Allelic Frequencies of 20 Visible Phenotype Variants in the Korean Population

The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction models in diverse ethnic populations. In this study, we selected potentially useful variations for forensic science that are associated with hair and eye color, iris pattern, and facial morphology, based on previous studies, and analyzed their frequencies in 1,920 Koreans. Among 20 single nucleotide polymorphisms (SNPs), 10 SNPs were polymorphic, 6 SNPs were very rare (minor allele frequency < 0.005), and 4 SNPs were monomorphic in the Korean population. Even though the usability of these SNPs should be verified by an association study in Koreans, this study provides 10 potential SNP markers for forensic science for externally visible characteristics in the Korean population.

Association Analysis of Reactive Oxygen Species-Hypertension Genes Discovered by Literature Mining

Oxidative stress, which results in an excessive product of reactive oxygen species (ROS), is one of the fundamental mechanisms of the development of hypertension. In the vascular system, ROS have physical and pathophysiological roles in vascular remodeling and endothelial dysfunction. In this study, ROS-hypertension-related genes were collected by the biological literature-mining tools, such as SciMiner and gene2pubmed, in order to identify the genes that would cause hypertension through ROS. Further, single nucleotide polymorphisms (SNPs) located within these gene regions were examined statistically for their association with hypertension in 6,419 Korean individuals, and pathway enrichment analysis using the associated genes was performed. The 2,945 SNPs of 237 ROS-hypertension genes were analyzed, and 68 genes were significantly associated with hypertension (p < 0.05). The most significant SNP was rs2889611 within MAPK8 (p = 2.70 x 10(-5); odds ratio, 0.82; confidence interval, 0.75 to 0.90). This study demonstrates that a text mining approach combined with association analysis may be useful to identify the candidate genes that cause hypertension through ROS or oxidative stress.

KARE Genomewide Association Study of Blood Pressure Using Imputed SNPs

The imputation of untyped SNPs enables researchers to validate association findings across SNP arrays and also enables them to test a large number of SNPs to reveal the fine structure of the association peak, facilitating interpretation of the results and the location of causal polymorphisms. In this study, we applied the imputation method to a genomewide association study and recapitulated the previously associated gene loci of blood pressure traits in Korean cohorts. A total of 1,827,004 SNPs were imputed by the IMPUTE program, and we conducted a genomewide association study for systolic and diastolic blood pressure. While no SNPs passed the Bonferroni correction p-value (p=2.74x10-8 for 1,827,004 SNPs), 12 novel loci for systolic blood pressure and 16 novel loci for diastolic blood pressure were detected by imputed SNPs, with 10-5

Identification of Genetic Variations in CBL, SORBS1, CRK, and RHOQ,Key Modulators in the CAP/TC10 Pathway of Insulin Signal Transduction and Their Association with Type 2 Diabetes Mellitus in the Korean Population

Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking,and fusion of vesicles containing the insulin- responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL , and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

The Effect of Extracellular Glutamate Release on Repetitive Transient Ischemic Injury in Global Ischemia Model

During operations, neurosurgeons usually perform multiple temporary occlusions of parental artery, possibly resulting in the neuronal damage. It is generally thought that neuronal damage by cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. In this study, we measured the dynamics of extracellular glutamate release in 11 vessel occlusion (VO) model to compare between single occlusion and repeated transient occlusions within short interval. Changes in cerebral blood flow were monitored by laser-Doppler flowmetry simultaneously with cortical glutamate level measured by amperometric biosensor. From real time monitoring of glutamate release in 11 VO model, the change of extracellular glutamate level in repeated transient occlusion group was smaller than that of single occlusion group, and the onset time of glutamate release in the second ischemic episode of repeated occlusion group was delayed compared to the first ischemic episode which was similar to that of single 10 min ischemic episode. These results suggested that repeated transient occlusion induces less glutamate release from neuronal cell than single occlusion, and the delayed onset time of glutamate release is attributed to endogeneous protective mechanism of ischemic tolerance.

Reference Values of Normal Femoral Condylar Cartilage Thickness and Its Ultrasonographic Findings

OBJECTIVE: To establish reference values for the femoral condylar cartilage thickness and to observe the cartilage clarity and sharpness between different age groups of healthy Koreans employing a ultrasonographic scanner. METHOD: 105 healthy volunteers from the ages of twenties to the fifties, without clinical signs of osteoarthritis were recruited for the study. Cartilage thickness at both intercondylar notch, medial condylar and lateral condylar area were obtained with 12 MHz linear transducer, in supine position under maximum flexion of the knee joints. Cartilage sharpness and clarity were also recorded in grade between 0 to 3. RESULTS: The thickness of cartilage significantly decreased with the increment of age (p<0.05) and the cartilage of the man was much thicker than woman (p=0.000). Grade of the sharpness and clarity was not different between age groups and the checked grade was mostly grade 1 and there was no grade 3. CONCLUSION: This study defines standard reference values of femoral condylar cartilage for musculoskeletal ultrasonography to prevent misinterpretation of thinning of cartilage thickness in difference age groups and sex. With these findings, we can specify the range of normal degenerative change of femoral condylar cartilage.

Protein Tyrosine Phosphatase N1 Gene Variants Associated with Type 2 Diabetes Mellitus and Its Related Phenotypes in the Korean Population

Protein phosphorylation at tyrosine residues is a key regulatory event that modulates insulin signal transduction. We studied the PTPN1 gene with regard to susceptibility to Korean type 2 diabetes mellitus (T2DM) and its related quantitative traits. A total of seven SNPs [g.36171G>A (rs941798), g.58166G>A (rs3787343), g.58208A>G (rs2909270), g.64840C>T (rs754118), g.69560C>G (rs6020612), g.69866G>A (rs718050), and g.69934T>G (rs3787343)] were selected based on frequency (>0.05), linkage disequilibrium (LD) status, and haplotype tagging status. We studied the seven SNPs in 483 unrelated patients with type 2 diabetes (age: 64+/-2.8 years, onset age: 56+/-8.1 years; 206 men, 277 women) and 1138 nondiabetic control subjects (age: 64+/-2.9; 516 men, 622 women). The SNP rs941798 had protective effects against T2DM with an odds ratio of 0.726 (C.I. 0.541~0.975) and p-value=0.034, but none of the remaining six SNPs was associated with T2DM. Also, rs941798 was associated with blood pressure, HDL cholesterol, insulin sensitivity. rs941798 also has been associated with T2DM in previous reports of Caucasian-American and Hispanic-American populations. This is the first report that shows an association between PTPN1 and T2DM in the Korean as well as Asian population.

Association between Prostaglandin-endoperoxide Synthase 2 (PTGS2) Polymorphisms and Blood Pressure in Korean Population

Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels, and chronical elevation of blood pressure is known as hypertension. Although hypertension is affected by genetic and environmental factors, the genetic background of hypertension is not fully understood. One of the candidate genetic factors, Prostaglandin-endoperoxide synthase 2 (PTGS2), is a membrane-bound enzyme, catalyzing the conversion of arachidonic acid to prostaglandin, and recently SNPs of PTGS2 gene was associated with hypertension in Japanese population. Therefore the association of PTGS2 polymorphisms was investigated with blood pressure in healthy Korean subjects, 470 unrelated individuals randomly selected from Ansung and Ansan cohorts. The 25 SNPs of PTGS2 gene were identified by the sequencing analysis of 24 Korean samples. Among identified polymorphisms, three SNPs (rs689466, -1329A>G; rs5275, +6365T>C; rs4648308, +8806G> A) were selected for further association analysis, and rs689466 located in promoter region was associated with blood pressure as well as triglyceride level in the blood. By in silico analysis, rs689466 locates in v-Myb transcription factor binding site, and the v-Myb site disappears when the SNP is changed from A to G nucleotide. Individuals with A/G and G/G genotype in rs689466 have higher blood pressure than those with A/A genotype, and the regression p-value is 0.008 for systolic and 0.004 for diastolic blood pressure. In summary, the PTGS2 polymorphism (rs689466) is associated with blood pressure in Asian populations based on this and Japanese studies, shedding light on it as a genetic risk marker of hypertension.

Optimization of Wet Fixation Methods for AFM Imaging of Human Fibroblast Cells

We investigated the effect by the chemical fixative on human fibroblast cells (HFCs) in order to make nano-scale images using by the atomic force microscopy (AFM). The cell fixation needed to be optimized as prerequisite step for the preparation before analysis. AFM imaging after optimal wet fixation can provide practical, simple and fast technique for scanning living cells. In this study, AFM images - topography and amplitude - and the optic images of HFCs which were fixed with phosphate buffered saline (PBS), 2:1 ethanol:acetic acid, 4% glutaraldehyde and 37% formaldehyde were compared respectively. The final effect by washing with PBS or distilled water (D.W.) was examined after 4% glutaraldehyde fixation. To determine the optimal fixation method for HFCs, we performed quantitative and qualitative analysis by the height profile, the presence of artifacts and the morphology of well-conserved fibroblastic topography image by AFM. From AFM image which showed fibroblastic cellular morphology and differential height value of cytoplasm (670+/-47 nm, n=10) and nucleus (847+/-32 nm, n=10) in HFCs, we proposed that wet fixation by 4% glutaraldehyde, followed by final washing with PBS, could be the most suitable preparation for AFM imaging of HFCs, which enable us to approach easily on living cells with the least shrinkage.

The Role of CD4(+)CD25(bright) Regulatory T Cells in the Maintenance of Pregnancy, Premature Rupture of Membranes, and Labor

PURPOSE: The aim of this study was to evaluate the changes of the regulatory T cell subset in peripheral blood caused by gestational age and premature rupture of membranes (PROM) with or without labor to verify the role of regulatory T cells in pregnancy. PATIENTS AND METHODS: We investigated regulatory T cell distribution in the peripheral blood of pregnancies during the first trimester (group I, n=2), the second trimester (group II, n=12), and the third trimester without PROM and labor (group III, n=15). In addition, we evaluated pregnancies in the third trimester complicated by PROM (group IV, n=4) and labor with no complication by PROM (Group V, n=5). Comparisons were made with non-pregnant controls (group VI, n=4) using flow cytometry. RESULTS: During uncomplicated pregnancy, the CD4(+)CD25(bright) regulatory T cell population decreased with advancing gestational age (group I=3.35+/-0.47, group II=2.91+/-1.44, group III=2.81+/-1.36, group VI=2.52+/-0.71, p=NS). When we compared group IV with group III and V to evaluate the changes of the regulatory T cells with PROM, the CD4(+)CD25(bright) regulatory T cell population was significantly decreased in group IV compared to group III (p=0.001) and group V (p=0.026). CONCLUSION: The present results revealed that the regulatory T cell population increased in early pregnancy but decreased in pregnancies complicated by PROM, indicating that regulatory T cells might be related to the maintenance of pregnancy.

The Levels of Circulating Vascular Endothelial Growth Factor and Soluble Flt-1 in Pregnancies Complicated by Preeclampsia

To evaluate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of preeclampsia, we measured total VEGF, free VEGF and soluble Flt-1 (sFlt-1) concentrations and determined their relationships. Maternal serum samples were collected from 20 patients with preeclampsia and 20 normotensive women with uncomplicated pregnancies matched with the patients with preeclampsia for gestational age and parity. The serum concentrations of total VEGF (2.39+/-0.75 vs. 0.28+/-0.14) and sFlt-1 (934.5+/-235.5 vs. 298.0+/-161.2) were significantly increased in the patients with preeclampsia compared to the women with uncomplicated pregnancies. However the serum concentration of free VEGF (21.5+/-6.3 vs. 134.0+/-16.3) was lower in patients with preeclampsia. There was a positive correlation between the serum concentrations of total VEGF and sFlt-1 with systolic and diastolic blood pressure, respectively. There was a negative correlation between the serum concentration of free VEGF and systolic and diastolic blood pressure. There was a strong negative correlation between free VEGF and sFlt-1 concentrations. In conclusion, we found VEGF and sFlt-1 were related to the pathogenesis of preeclampsia. Although reduced concentrations of free VEGF might interfere with endothelial cell function and survival, further studies are required to clarify its specific role in the pathogenesis of preeclampsia.

A Case of Chromosome 16 Disorder with Unilateral Multicystic Displastic Kidney

The survival rate of neonates with aberrations of chromosome 16 is very low because they are incompatable with life. We encountered a case of a chromosome 16 aberration in a female neonate who showed multiple congenital malformations suggestive of chromosomal anomaly including round face, hypertelorism, low-set ears, cleft palate, multiple heart anomalies, bilateral hearing loss, right multicystic dysplastic kidey, proximally located thumbs, planovalgus, and muscle hypotonia. We report the case with a brief review of the literature.