Objective: : The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. Methods: : Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. Results: : Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. Conclusion : BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Purpose: Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. Materials and Methods: Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. Results: From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. Conclusion We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

Objective: : To evaluate the interactions among differentially expressed autophagy and mitophagy markers in subarachnoid hemorrhage (SAH) patients with delayed cerebral ischemia (DCI). Methods: : The expression data of autophagy and mitophagy-related makers in the cerebrospinal fluid (CSF) cells was analyzed by real-time reverse transcription-polymerase chain reaction and Western blotting. The markers included death-associated protein kinase (DAPK)-1, BCL2 interacting protein 3 like (BNIP3L), Bcl-1 antagonist X, phosphatase and tensin homolog-induced kinase (PINK), Unc-51 like autophagy activating kinase 1, nuclear dot protein 52, and p62. In silico functional analyses including gene ontology enrichment and the protein-protein interaction network were performed. Results: : A total of 56 SAH patients were included and 22 (38.6%) of them experienced DCI. The DCI patients had significantly increased mRNA levels of DAPK1, BNIP3L, and PINK1, and increased expression of BECN1 compared to the non-DCI patients. The most enriched biological process was the positive regulation of autophagy, followed by the response to mitochondrial depolarization. The molecular functions ubiquitin-like protein ligase binding and ubiquitin-protein ligase binding were enriched. In the cluster of cellular components, Lewy bodies and the phagophore assembly site were enriched. BECN1 was the most connected gene among the differentially expressed markers related to autophagy and mitophagy in the development of DCI. Conclusion : Our study may provide novel insight into mitochondrial dysfunction in DCI pathogenesis.

Background: This study investigated trends in the prevalence of major depressive disorder (MDD) by sociodemographic factors in South Korea. Methods: National samples of the general population aged 18 years or older collected from the nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001 (n = 6,206), 2006 (n = 6,466), and 2011 (n = 5,986) were used. For MDD diagnosis, we conducted face-to-face interviews using the Korean version of the Composite International Diagnostic Interview. We performed logistic regression analyses stratified by gender, after adjusting for other sociodemographic variables, to calculate the 2006-to-2001 odds ratio (OR) and 2011-to-2001 OR by subgroups of sociodemographic factors to explore the association of MDD prevalence with sociodemographic factors over time. Results: The prevalence of MDD in the general population of South Korea increased steadily from 2001, to 2006, and to 2011 (1.6%, 2.5%, and 3.1%, respectively). Among the men, the prevalence of MDD continued to increase significantly in 18–29 years of age group (2006: adjusted OR [AOR], 3.32; 2011: AOR, 7.42), at-risk drinking group (2006: AOR, 3.56; 2011: AOR, 4.77), and not living with a partner group (2006: AOR, 3.24; 2011: AOR, 3.25).Meanwhile, among the women, the prevalence of MDD continued to significantly increase in the below-average household income group (2006: AOR, 2.58; 2011: AOR, 2.59), at-risk drinking group (2006: AOR, 2.02; 2011: AOR, 2.47), and unemployed group (2006: AOR, 1.48; 2011: AOR, 2.04). Conclusion This study may provide significant information for public policymakers to allocate sufficient health resources on MDD to vulnerable groups, particularly, men aged 18–29 years and women living in households with below-average income, and for clinicians to develop appropriate screening and treatment modalities for MDD.

Background: This study investigated trends in the prevalence of major depressive disorder (MDD) by sociodemographic factors in South Korea. Methods: National samples of the general population aged 18 years or older collected from the nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001 (n = 6,206), 2006 (n = 6,466), and 2011 (n = 5,986) were used. For MDD diagnosis, we conducted face-to-face interviews using the Korean version of the Composite International Diagnostic Interview. We performed logistic regression analyses stratified by gender, after adjusting for other sociodemographic variables, to calculate the 2006-to-2001 odds ratio (OR) and 2011-to-2001 OR by subgroups of sociodemographic factors to explore the association of MDD prevalence with sociodemographic factors over time. Results: The prevalence of MDD in the general population of South Korea increased steadily from 2001, to 2006, and to 2011 (1.6%, 2.5%, and 3.1%, respectively). Among the men, the prevalence of MDD continued to increase significantly in 18–29 years of age group (2006: adjusted OR [AOR], 3.32; 2011: AOR, 7.42), at-risk drinking group (2006: AOR, 3.56; 2011: AOR, 4.77), and not living with a partner group (2006: AOR, 3.24; 2011: AOR, 3.25).Meanwhile, among the women, the prevalence of MDD continued to significantly increase in the below-average household income group (2006: AOR, 2.58; 2011: AOR, 2.59), at-risk drinking group (2006: AOR, 2.02; 2011: AOR, 2.47), and unemployed group (2006: AOR, 1.48; 2011: AOR, 2.04). Conclusion This study may provide significant information for public policymakers to allocate sufficient health resources on MDD to vulnerable groups, particularly, men aged 18–29 years and women living in households with below-average income, and for clinicians to develop appropriate screening and treatment modalities for MDD.

Background: The aim of this study was to evaluate clinical experience with arthroscopic debridement for septic arthritis of the shoulder joint and to report on our patient outcomes. Methods: The retrospective analysis included 36 shoulders (male:female, 15:21), contributed by 35 patients (mean age, 63.8 years) treated by arthroscopy for septic arthritis of the shoulder between November 2003 and February 2016. The mean follow-up period was 14.3 months (range, 12–33 months). An additional posterolateral portal and a 70º arthroscope was used to access the posteroinferior glenohumeral (GH) joint and posteroinferior subacromial (SA) space, respectively. Irrigation was performed with a large volume of fluid (25.1±8.1 L). Multiple suction drains (average, 3.3 drains) were inserted into the GH joint and SA space and removed 8.9±4.3 days after surgery. Intravenous antibiotics were administered for 3.9±1.8 weeks after surgery, followed by oral antibiotic treatment for another 3.6±1.9 weeks. Results: Among the 36 shoulders, reoperation was required in two cases (5.6%). The average range of motion achieved was 150.0º for forward flexion and T9 for internal rotation. The mean simple shoulder test score was 7.9±3.6 points. Nineteen shoulders (52.8%) had acupuncture or injection history prior to the infection. Pathogens were identified in 15 shoulders, with Staphylococcus aureus being the most commonly identified pathogen (10/15). Both the GH joint and the SA space were involved in 21 shoulders, while 14 cases involved only the GH joint and one case involved only the SA space. Conclusions Complete debridement using an additional posterolateral portal and 70º arthroscope, a large volume of irrigation with >20 L of saline, and multiple suction drains may reduce the reoperation rate.

PURPOSE: Lysyl oxidase (LOX) controls the cross-linking and maturation of elastin and collagen fibers. In this study, we investigated the association between LOX gene polymorphisms and intracranial aneurysm (IA) formation in a homogeneous Korean population. MATERIALS AND METHODS: This cross-sectional study involved 80 age-sex matched patients with IA and controls. Fisher's exact test was performed to analyze allelic associations between ten single nucleotide polymorphisms (SNPs) and IA, including 41 ruptured and 39 unruptured cases. Haplotype-specific associations were analyzed using the omnibus test estimating asymptotic chi-square statistics. RESULTS: Of ten SNPs, three SNPs (rs2303656, rs3900446, and rs763497) were significantly associated with IA (p<0.01). The C allele of rs3900446 was significantly related to increased IA risk with a significant threshold [odds ratio (OR)=20.15, p=4.8×10⁻⁵]. Meanwhile, the A allele of rs2303656 showed a preventive effect against IA formation (p=8.2×10⁻⁴). Seventeen of 247 haplotype structures showed a suggestive association with IA (asymptotic p<0.001). Of ten SNP haplotype combinations, the CG combination of rs3900446 and rs763497 reached Bonferroni-adjusted significant threshold in IA patients (minor haplotype frequency=0.113, asymptotic p=1.3×10⁻⁵). However, there was no association between aneurysm rupture and the LOX gene. CONCLUSION: This preliminary study indicated that LOX gene polymorphisms, such as rs2303656, rs3900446, and rs763497, may play crucial roles in IA formation in the Korean population. Our novel findings need to be validated in a large-scale independent population.
Alleles ; Aneurysm ; Collagen ; Cross-Sectional Studies ; Elastin ; Haplotypes ; Humans ; Intracranial Aneurysm* ; Polymorphism, Single Nucleotide ; Protein-Lysine 6-Oxidase* ; Rupture ; Subarachnoid Hemorrhage

PURPOSE: Chitin is a potent adjuvant in the development of immune response to inhaled allergens in the airways. According to other studies, chitin is known as multi-faced adjuvants which can induce Th2 responses. Recently, we found that TNF-α is a key mediator in the development of Th2 cell response to inhaled allergens. Here, we evaluated the immunologic mechanisms in the development of airway hypersensitivity to inhaled allergens, enhanced by house dust mite (HDM)-derived chitin. METHODS: The role of TNF-α and TLRs was evaluated in an airway hypersensitivity mouse model induced by a sensitization with an allergen (ovalbumin, OVA) and HDM-derived chitin using mice with the null mutation of target genes. RESULTS: The present study showed that airway sensitization with HDM-derived chitin plus OVA enhanced OVA-induced airway inflammation v. OVA alone. This phenotype was associated with the increased expression of Th1, Th2, and Th17 cytokines and also with the enhanced production of OVA-specific IgE, IgG1, and IgG2a. As for T cell responses, OVA-specific Th2 cell response, enhanced by chitin, was abolished by the treatment of chitinase, whereas Th1 and Th17 cell responses enhanced by this treatment. Moreover, the null mutation of the TNF-α gene revealed similar effects as the chitinase treatment. In contrast, all the OVA-specific T cell responses, enhanced by chitin, were blocked by the absence of TLR2, but not of TLR1, TLR4, or TLR6. CONCLUSIONS: In conclusion, these data suggest that HDM-derived chitin may enhance airway hypersensitivity to inhaled allergens, via the TLR2-dependent pathway, and that chitin-induced TNF-α can be a key mediator in the development of Th2 cell response to inhaled allergens.
Allergens* ; Animals ; Chitin* ; Chitinase ; Cytokines ; Dust* ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulin G ; Inflammation ; Mice ; Ovum ; Phenotype ; Pyroglyphidae ; Th17 Cells ; Th2 Cells*

OBJECTIVES: The aim of this study is to evaluate difference of somatic symptoms of anxiety disorder and major depressive disorder and domainal association with suicidal idealization, plan, and attempts. METHODS: A total of 359 adults diagnosed with major depressive disorder and anxiety disorder of last one year participated. Participants interviewed with certain sections of Korean version of Composite International Diagnostic interview of CIDI. Sections of interests includes questionnaires regarding somatic symptoms and suicidal idea, plan and attempts of last one year. RESULTS: Chest pain shows more prevalence in major depressive disorder. Symptoms of Headache and loose stool are more prevalent in anxiety disorder. Difficulty in equilibrium and fainting spells are more common somatic complaints of co-diagnosis states of anxiety disorder and major depressive disorder. Comparing 3 domains of pain symptoms, gastrointestinal symptoms and pseudo-neurological symptoms, pain symptom domains, gastrointestinal symptoms domain shows significant statistic difference between diagnosis. Average somatic symptom numbers of each symptom domains increase through suicidal idealization, plan and attempt, accordingly. CONCLUSIONS: Our finding shows some of somatic symptoms are more prevalent at certain diagnosis. Since increasing numbers of somatic complaints of each symptom domains goes with the suicidal idealization to suicidal attempts, proper psychiatric evaluation and consultations are crucial for patients with numerous somatic complaints in non-psychiatric clinical settings.
Adult ; Anxiety Disorders* ; Anxiety* ; Chest Pain ; Depression ; Depressive Disorder, Major* ; Diagnosis ; Headache ; Humans ; Prevalence ; Referral and Consultation ; Suicide ; Syncope