significant advances have been made in understanding the biological underpinnings of post-traumatic stress disorder(PTSD), particularly in the field of genetics and neuroimaging. Association studies in candidate genes related with hypothalamic-pituitary-adrenal axis, monoamines including serotonin, dopamine and noradrenaline, and proteins including FK506-binding protein 5 and brain-derived neurotrophic factor have provided important insights with regard to the vulnerability factors in PTSD. Genome-wide association studies and epigenetic studies may provide further information for the role of genes in the pathophysiology of PTSD. Hippocampus, medial prefrontal cortex, anterior cingulated cortex and amygdala have been considered as key structures that underlie PTSD pathophysiology. Future research that combines genetic and neuroimaging information may provide an opportunity for a more comprehensive understanding of PTSD.
Amygdala ; Axis, Cervical Vertebra ; Brain-Derived Neurotrophic Factor ; Dopamine ; Epigenomics ; Genome-Wide Association Study ; Hippocampus ; Neuroimaging ; Norepinephrine ; Prefrontal Cortex ; Proteins ; Serotonin ; Stress Disorders, Post-Traumatic ; Tacrolimus Binding Proteins

OBJECTIVES: The extract of Hizikia fusiformis is known to exhibit anticancer, antiatopic and antioxidant activities. We aimed to investigate the extract of H. fusiformis on allergic rhinitis inflammation in a mouse model. METHODS: The 4-week-old BALB/c mice were randomly assigned into four groups: group A, control group (n=9); group B, allergic rhinitis group (n=10); group C (n=10) received 300 mg/kg of H. fusiformis during nasal challenging period; group D (n=10) received 600 mg/kg of H. fusiformis during general sensitization period and 300 mg/kg of H. fusiformis during nasal challenging period. Allergic inflammation was made with ovalbumin (OVA) and alum then challenged intranasally with OVA. H. fusiformis was intraperitoneally administered 3 hours before the OVA administration. Allergic symptom score and the levels of immunoglobulin G1 (IgG1), IgG2a, OVA-specific IgE antibodies, levels of cytokines in the nasal mucosa and in spleen cell culture supernatant, such as tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-13, and IL-10 were assessed. The percentage of regulatory T cell was analyzed by flow cytometry. Eosinophilic infiltration and goblet cell hyperplasia were also evaluated. RESULTS: H. fusiformis administered groups C and D showed significant inhibitory effects on nasal symptoms, IL-13 mRNA expression and eosinophil infiltration/goblet cell hyperplasia in the nasal tissue; OVA-specific IgE production in serum (P<0.05). In group D, H. fusiformis treatment downregulated IL-4, IL-5, IL-13, TNF-α, and IL-10 cytokine expression in splenocyte culture as well as significantly decreased IgG2a, IgG1 levels in serum compared with group B (P<0.05). However, the expressions of IL-5, interferon-γ and forkhead box P3 mRNA did not change in groups C and D. CONCLUSION: H. fusiformis could induce antiallergic inflammation by suppressing the T-helper type 2 cytokine production (IL-13) locally and systemically, OVA-specific IgE formation, goblet cell hyperplasia, and eosinophilic infiltration in a mouse model of allergic rhinitis. Thus, H. fusiformis could be considered as a potential therapeutic agent in treating allergic rhinitis.
Animals ; Antibodies ; Cell Culture Techniques ; Cytokines ; Eosinophils ; Flow Cytometry ; Goblet Cells ; Hyperplasia ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Mice ; Nasal Mucosa ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Spleen ; Th2 Cells ; Tumor Necrosis Factor-alpha

Background: Reproductive factors such as childbirth, gravidity, age of menarche, breastfeeding, and use of oral contraceptives could affect the risk of cardiovascular disease in women. This study aimed to investigate the relationship between reproductive factors and cardiovascular disease in postmenopausal women in Korea. Methods: This study included 2,310 women aged ≥45 years who experienced natural menopause and participated in the 7th Korea National Health and Nutrition Examination Survey (2016–2017). Cardiovascular disease was defined as myocardial infarction, angina, and stroke. Coronary heart disease was defined as myocardial infarction and angina. Logistic regression was performed to calculate the odds ratio of cardiovascular disease with respect to each reproductive factor. Results: Women who breastfed for longer duration (≥24 months) group had a 3-fold higher risk of cardiovascular disease and 4–5-fold higher risk of coronary heart disease than those in the non-breastfeeding group. One-time pregnancy was associated with a higher risk of coronary heart disease than gravidity of 6. Early menarche (≤11 years of age) was associated with a high risk of stroke. Women who had a history of using oral contraceptives were at low risk of stroke. Conclusion Breastfeeding, low gravidity, and early menarche were associated with an increased risk of cardiovascular disease, whereas use of oral contraceptives was associated with reduced risk of stroke. However, some of these results were different from previous reports. Therefore, further studies are needed to identify the relationship between reproductive factors and cardiovascular disease in women.

BACKGROUND: Therapeutic plasma exchange (TPE) for desensitization in ABO incompatible kidney transplantation (KT) has raised concerns regarding efficiency and safety. The purpose of this study was to determine the number of TPE prior to KT required to reach target titer for KT according to ABO blood groups. METHODS: The distribution of ABO antibody (Ab) titer of 117 patients was investigated. The relationship between initial ABO Ab and number of TPEs required to reach target titer to ≤1:8 prior to KT was evaluated retrospectively according to blood groups and ABO Ab classes. RESULTS: The initial IgG ABO Ab titers were the highest in blood O group recipients, and the average number±standard deviations (range) of TPEs performed prior to ABO incompatible KT was 3.0±1.1 (0~5) in blood group A, 3.7±1.5 (0~8) in blood group B, and 5.3±1.9 (2~13) in blood group O, respectively. The best correlation was observed in the linear relationship between initial ABO Ab titer and number of TPEs required (y=0.6829x+0.0523, R2=0.946, x=log2 initial ABO Ab titer, y=number of TPE required), regardless of the specific ABO blood group. CONCLUSION: The number of TPEs can be highly deduced from initial ABO Ab titer and our developed equation in desensitization programs would help increase the efficiency of TPE and patient safety.
Blood Group Antigens ; Blood Group Incompatibility ; Humans ; Immunoglobulin G ; Kidney Transplantation* ; Kidney* ; Patient Safety ; Plasma Exchange* ; Plasma* ; Retrospective Studies

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. Although viral reactivation is associated with DRESS syndrome, its role in TEN remains unclear. An 80-year-old woman visited our hospital because of fever and skin eruption. DRESS syndrome was diagnosed and was thought to caused by the use of the drug allopurinol. She was treated by discontinuation of the drug and administration of systemic steroids. She recovered from DRESS syndrome and was discharged from the hospital with tapering doses of steroids prescribed. One week after discharge, she visited our hospital again as the skin rash recurred and oral pain as well as oral and ocular mucosal lesions developed. In addition to the skin rash, blisters and Nikolsky's sign that were different from the skin lesions present in the previous DRESS syndrome were observed. Unlike those in DRESS syndrome, the viral serological test results were positive for anti-cytomegalovirus (CMV) IgM and CMV polymerase chain reaction. Therefore, it was thought that TEN was due to reactivation of CMV and she was treated this with ganciclovir and intravenous immunoglobulin. Here, we report a case of TEN caused by viral reactivation after DRESS syndrome developed after use of allopurinol which recovered after steroid treatment.
Aged, 80 and over ; Allopurinol ; Blister ; Cytomegalovirus Infections ; Cytomegalovirus ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Exanthema ; Female ; Fever ; Ganciclovir ; Humans ; Immunoglobulin M ; Immunoglobulins ; Polymerase Chain Reaction ; Serologic Tests ; Skin ; Steroids ; Stevens-Johnson Syndrome

Purpose: Asthma phenotypes are often defined by relative cell counts of airway granulocytes. Induced sputum test results enable clinicians to determine the inflammatory phenotype of asthma based on the eosinophil and neutrophil counts. This study aimed to investigate clinical characteristics of patients with asthma according to the inflammatory phenotype of their condition. Methods: Data from 107 patients with asthma reported at a single tertiary allergy center in Korea during October 2016 to January 2019 were obtained. Patients were categorized into 4 asthma phenotypes based on the cell counts on the induced sputum test: eosinophilic, neutrophilic, mixed, and paucigranulocytic types. Blood eosinophil count, total IgE level, eosinophil cationic protein, spirometric measurements, fractional exhaled nitric oxide, atopy based on the skin prick test, PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) in methacholine provocation test, type of asthma controller used, frequency of exacerbation, and use of systemic corticosteroids were examined. Results: The frequency of phenotype is as follows: eosinophilic (21.4%), neutrophilic (34.8%), mixed (13.4%), and paucigranulocytic types (30.4%). During the observation period, the proportion of patients who experienced an exacerbation and received systemic glucocorticosteroids were significantly lower in patients with the paucigranulocytic type of asthma than in those with the mixed type of asthma (6.3% vs. 40.0%; P = 0.007 and 5.9% vs. 40.0%; P = 0.004, respectively). Conclusion Paucigranulocytic asthma may be associated with lower incidence rates of asthma exacerbation and systemic corticosteroid use than the other phenotypes, classified according to induced sputum test results.

OBJECTIVE: A widely applicable, non-invasive screening method for non-alcoholic fatty liver disease (NAFLD) is needed. We aimed to develop and validate an index combining computed tomography (CT) and routine clinical data for screening for NAFLD in a large cohort of adults with pathologically proven NAFLD.MATERIALS AND METHODS: This retrospective study included 2218 living liver donors who had undergone liver biopsy and CT within a span of 3 days. Donors were randomized 2:1 into development and test cohorts. CT(L-S) was measured by subtracting splenic attenuation from hepatic attenuation on non-enhanced CT. Multivariable logistic regression analysis of the development cohort was utilized to develop a clinical-CT index predicting pathologically proven NAFLD. The diagnostic performance was evaluated by analyzing the areas under the receiver operating characteristic curve (AUC). The cutoffs for the clinical-CT index were determined for 90% sensitivity and 90% specificity in the development cohort, and their diagnostic performance was evaluated in the test cohort.RESULTS: The clinical-CT index included CT(L-S), body mass index, and aspartate transaminase and triglyceride concentrations. In the test cohort, the clinical-CT index (AUC, 0.81) outperformed CT(L-S) (0.74; p < 0.001) and clinical indices (0.73–0.75; p < 0.001) in diagnosing NAFLD. A cutoff of ≥ 46 had a sensitivity of 89% and a specificity of 41%, whereas a cutoff of ≥ 56.5 had a sensitivity of 57% and a specificity of 89%.CONCLUSION: The clinical-CT index is more accurate than CT(L-S) and clinical indices alone for the diagnosis of NAFLD and may be clinically useful in screening for NAFLD.

The sibling relationship and its potential impact on neurodevelopment and mental health are important areas of neuroscientific research. Validation of the tools assessing the quality of the sibling relationship would be the first essential step for conducting neurobiological and psychosocial studies related to the sibling relationship. However, to the best of our knowledge, no sibling relationship assessment tools have been empirically validated in Korean. We aimed to evaluate the psychometric properties of the Korean version of the Lifespan Sibling Relationship Scale (LSRS), which is one of the most commonly used self-report questionnaires to assess the quality of the sibling relationship. A total of 109 adults completed a series of self-report questionnaires including the LSRS, the mental health subscale of the Medical Outcomes Study-Short Form 36 version 2 (SF36v2), the Satisfaction with Life Scale (SLS), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). The internal consistency, subscale intercorrelations, one-week test-retest reliability, convergent validity, divergent validity, and the construct validity were assessed. All six subscale scores and the total score of the LSRS demonstrated good internal consistency (Cronbach's alpha=0.85-0.94) and good test-retest reliability (intraclass correlation coefficient=0.77-0.92). Correlations of the LSRS with the SF36v2 mental health score (r=0.32, p=0.01) and with the SLS (r=0.27, p=0.04) supported the good convergent validity. The divergent validity was shown by the non-significant correlation of the LSRS with the MC-SDS (r=0.15, p=0.26). Two factors were extracted through factor analysis, which explained 78.63% of the total variance. The three Adult subscales loaded on the first factor and the three Child subscales loaded on the second factor. Results suggest that the Korean version of the LSRS is a reliable and valid tool for examining the sibling relationship.
Adult ; Child ; Humans ; Mental Health ; Psychometrics ; Reproducibility of Results* ; Siblings* ; Social Desirability ; Surveys and Questionnaires

PURPOSE: Prader-Willi syndrome (PWS) is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS. METHODS: A total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000-2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD) group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis. RESULTS: There was no statistical significance in seasonal variation in births of the total 211 patients with PWS (chi2=7.2522, P=0.2982). However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05). In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2). The UPD group showed the peak birth month in spring; however, this result was not statistically significant (chi2=3.39, P=0.1836). CONCLUSION: Correlation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.
Chromosomes, Human, Pair 15* ; Humans ; Methylation ; Parturition* ; Polymerase Chain Reaction ; Prader-Willi Syndrome* ; Seasons* ; Uniparental Disomy

PURPOSE: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. MATERIALS AND METHODS: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed > or = 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase-polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients. RESULTS: CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393). CONCLUSION: DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.
Gastric Mucosa ; Humans ; Lymph Nodes* ; Neoplasm Metastasis* ; Oligonucleotide Array Sequence Analysis ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Stomach Neoplasms*