Background: Migraine patients have a higher frequency of suicidality than people without migraine. The aim of this study was to identify suicidality and its risk factors in migraine patients. Methods: We enrolled 358 migraine patients from 11 hospitals. We collected data regarding their clinical characteristics and the patients completes the questionnaires. We also interviewed patients with the Mini International Neuropsychiatric Interview (MINI)plus version 5.0.0 to identify their suicidality. The International Classification of Headache Disorders, third edition, beta version was used in headache diagnosis. Results: The frequency of suicidality in migraine patients was 118 (33.0%). Migraine patients with suicidality were more likely to have a major depressive disorder or generalized anxiety disorder than those without suicidality. Among variables, risk factors for suicidality in migraine patients were female (odds ratio [OR], 4.110; 95% confidence interval [CI], 1.55310.878; p=0.004), attack duration (OR, 2.559; 95% CI, 1.2105.413; p=0.011), Patient Health Questionnaire9 (OR, 1.111; 95% CI, 1.0381.189; p=0.002), and Generalized Anxiety Disorder7 (OR, 1.194; 95% CI, 1.1011.294; p<0.001). Conclusions Suicidality in migraine patients is common. Therefore, clinicians who take care of migraine patients should be concerned about suicidality and its risk factors such as female gender, attack duration, depression or anxiety.

Objectives: . Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods: . This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results: . Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion . We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines (TNFα, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes (TNFα, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.
Animals ; Blotting, Western ; Coculture Techniques ; Cytokines ; Diet ; Diet, High-Fat ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Fatty Liver ; Heme Oxygenase-1* ; Heme* ; Hepatocytes ; Humans ; Inflammation* ; Insulin Resistance ; Liver ; Macrophages* ; Male ; Mice ; NF-E2-Related Factor 2 ; Obesity ; Phenotype* ; Quercetin* ; Up-Regulation

PURPOSE: Collectin family is an important component of innate immunity, of which surfactant protein (SP)-D and mannose-binding lectin (MBL) are the most characterized. We examined SP-D and MBL in young children with acute respiratory syncytial virus (RSV) bronchiolitis. METHODS: Sixty-three children (< or =24 months of age) admitted with the first RSV bronchiolitis during 2 epidemics and followed for 1 year after discharge were enrolled. The patients were defined as severe group when they had 2 of followings during admission: hypoxemia (<92% oxygen saturation), rapid breathing (and/or lower chest wall indrawing), and >7 days of hospital stay. All children were evaluated if they had recurrent wheezing during follow-up. SP-D and MBL were measured using enzyme-linked immunosorbent assay in serum collected on admission and compared with controls. Their levels were evaluated in relation to the symptom severity during admission and recurrence of wheezing after discharge. RESULTS: Serum SP-D increased significantly in the patients (P<0.01), but MBL showed no difference compared to the controls. SP-D levels were significantly higher in severe group compared with nonsevere group (P<0.05). SP-D levels in the patients with recurrent wheezing after discharge were significantly higher than in those without (P<0.05). MBL showed no difference in relation to the symptom severity or recurrence of wheezing. CONCLUSION: Our study showed that serum SP-D was associated with the severity of RSV bronchiolitis and suggests that it might be a biomarker of lung injury and recurrence of wheezing illnesses in the young children admitted with their first RSV bronchiolitis.
Anoxia ; Bronchiolitis ; Child ; Collectins ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Humans ; Immunity, Innate ; Infant ; Length of Stay ; Lung Injury ; Mannose-Binding Lectin ; Oxygen ; Pulmonary Surfactant-Associated Protein D ; Recurrence ; Respiration ; Respiratory Sounds ; Respiratory Syncytial Viruses ; Thoracic Wall

PURPOSE: Soluble ST2 (sST2) has been reported to regulate Th2 response. In this study, serum levels of sST2 and other cytokines were measured in recurrent early wheezers and asthmatic children. We aimed to investigate if there are any differences or similarities in Th1 or Th2 response between those two patient groups. METHODS: Fifty-nine patients admitted with exacerbation of wheezing or asthma were enrolled. Two patient groups were defined: children with atopic asthma (> or =6 years, n=21) and recurrent early wheezers (< or =2 years, n=38). Recurrent early wheezers were divided based on their atopic status: 19 were atopic and 19 were nonatopic. sST2, interleukin (IL) 33, IL-5, and interferon (IFN)-gamma were measured in serum samples collected on admission. Cytokine levels in both patient groups were compared with their age-matched controls and evaluated the relationship with blood eosinophils, serum IgE levels, and also with the severity of symptom. RESULTS: sST2 and IL-5 were significantly increased both in asthmatic children (P=0.02, P=0.004) and recurrent early wheezers (P=0.01, P=0.001) compared to their age-matched controls. IL-5 was significantly higher in atopic wheezers compared with non-atopic wheezers (P=0.04). Severity score showed a positive correlation with sST2 and IFN-gamma in asthmatic children, but only with IFN-gamma in early wheezers. There was an inverse correlation between sST2 and blood eosinophil counts both in asthmatic children and atopic recurrent wheezers. CONCLUSION: Our study suggests that sST2 might regulate allergic inflammation by suppressing eosinophilia and play an important role in pathophysiology of acute exacerbation of wheezing or asthma both in asthmatic children and early wheezers.
Asthma ; Child* ; Cytokines ; Eosinophilia ; Eosinophils ; Humans ; Immunoglobulin E ; Inflammation ; Interferons ; Interleukin-5 ; Interleukins ; Respiratory Sounds

PURPOSE: Interleukin (IL)-33, a member of the IL-1 cytokine family, is considered to be important for innate-type mucosal immunity of the lung and also has been suggested to induce Th2-type immune responses. We aimed to investigate if IL-33 is involved in airway inflammation due to respiratory syncytial virus (RSV) infection in young children. METHODS: Thirty-eight infants (< or =24 months of age) admitted with their first episode of RSV bronchiolitis were enrolled in the study. Atopy was defined by having at least 1 allergen-specific immunoglobulin E (IgE), positive result to skin prick test, or high serum IgE levels. The patients were assessed to have severe symptoms when they had > or =2 of the following clinical findings: hypoxemia (<92% oxygen saturation), rapid breathing (and/or lower chest wall indrawing), and >7 days of hospital stay. The levels of IL-33 and the IL-33 receptor (sST2) were measured using enzyme-linked immunosorbent assay in nasal secretion samples collected from the patients on admission and compared with 20 age-matched controls. We also investigated the levels of IL-33 and sST2 in relation to the atopic status and symptom severity of the patients. RESULTS: Nasal IL-33 levels in the patients with acute RSV bronchiolitis were significantly increased (P<0.05), but sST2 showed no difference compared to the controls. Neither IL-33 nor sST2 showed significant difference in relation to the atopic status or severity of symptoms. CONCLUSION: Our study showed significantly increased IL-33 in the nasal secretions of the young infants admitted with acute RSV bronchiolitis and suggests that IL-33 is involved in the pathogenesis of RSV-induced airway inflammation.
Anoxia ; Bronchiolitis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunity, Mucosal ; Immunoglobulin E ; Immunoglobulins ; Infant ; Inflammation ; Interleukin-1 ; Interleukins ; Length of Stay ; Lung ; Oxygen ; Respiration ; Respiratory Syncytial Viruses ; Skin ; Thoracic Wall

PURPOSE: In the present study, we investigated the clinical characteristics of tuberculosis in school-age children and adolescents, which is important as a reservoir for future disease burden. METHODS: Ninety patients, aged from 6 to 18 years, who were diagnosed and treated with tuberculosis during the period from January 2005 to July 2011, were enrolled. We retrospectively analyzed the medical records and investigated clinical characteristics of the patients. RESULTS: Eight patients were 6 to 12 (9%) and 82 were over 13 years of age (91%). There was a significantly higher percentage of males than females in the latter age group (P<0.01). Route of infection was not confirmed in 74 patients, and 16 patients were diagnosed through the school or military medical examinations with no clinical symptoms. Seventy patients (78%) were presented with pulmonary tuberculosis. Chronic persistent coughing was the most common presenting symptom, and both upper lobes were most frequently involved. Nineteen patients over 13 years of age had adult-type cavitary tuberculosis. The positive results for acid-fast smears or cultures were not high, and the rate of positive tuberculin skin test was 88%. The most frequent adverse effects of anti-tuberculosis treatment were hepatotoxicity, hyperuricemia, and gastrointestinal disorders. The duration of the treatment was much prolonged in 8 patients who had drug-resistant tuberculosis. CONCLUSION: Our study showed that pulmonary tuberculosis should be suspected in the adolescents who have prolonged respiratory symptoms. It also indicates that pulmonary tuberculosis in adolescents has similar characteristics to tuberculosis in adults, which suggests the potential important role of adolescent tuberculosis in community disease transmission.
Adolescent ; Adult ; Aged ; Child ; Cough ; Female ; Humans ; Hyperuricemia ; Male ; Medical Records ; Military Personnel ; Retrospective Studies ; Skin Tests ; Tuberculin ; Tuberculosis ; Tuberculosis, Pulmonary

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.
Adult ; Alcohol Dehydrogenase/*genetics ; Alcoholism/enzymology/genetics ; Aldehyde Dehydrogenase/*genetics ; Central Nervous System Depressants/pharmacokinetics ; Cytochrome P-450 CYP2E1/*genetics ; Ethanol/pharmacokinetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Human ; Korea ; Liver Cirrhosis, Alcoholic/enzymology/*genetics ; Male ; Middle Age ; *Polymorphism (Genetics)

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of lamivudine in patients with HBeAg-negative and HBV DNA-positive chronic liver disease. METHODS: Twenty-four chronic liver disease patients were enrolled whose serology had common characteristics of HBeAg (-), and anti-HBe (+) but HBV DNA (+). All had elevated alanine aminotransferase (ALT) levels. 150mg of lamivudine was given orally once daily for more than 6 months. The goal of this treatment was the elimination of HBV DNA in serum and normalization of ALT level. Once HBV DNA disappearance and ALT normalization were observed, lamivudine was continued for two additional months. HBeAg, anti-HBe, HBV DNA and ALT were followed up every 1-2 month during, and after, treatment. RESULTS: Median duration of treatment was seven months. HBV DNA became undetectable after a median one month of treatment and ALT activity was normalized in all 24 patients within six months. Among the sixteen patients who were followed for more than 12 months after cessation of treatment, six relapsed. The cumulative relapse rate at 12 months was 37.5%. CONCLUSION: Lamivudine suppresses HBV replication effectively and normalizes serum ALT in patients with HBeAg-negative and HBV DNA-positive chronic liver disease. The relapse rate after cessation of treatment seems to be relatively low.
Alanine Transaminase ; DNA ; Hepatitis B e Antigens ; Hepatitis B virus ; Humans ; Lamivudine* ; Liver Diseases* ; Liver* ; Recurrence ; Withholding Treatment

The occurrence of disseminated tuberculosis in combination with acute leukemia is rare. A 28 year old male undergoing induction chemotherapy for AML presented with fever of unknown origin. Upon the studies to make the diagnosis this case turned out to be disseminated tuberculosis including meningitis. The chest CT showed multiple enlarged mediastinal lymphadenopathy. The Brain CT showed noncommunicating obstructive hydrocephalus. Disseminated tuberculosis was pathologically proven by theliver, bone marrow and mediastinal lymph node biopsies. As clinical course improved, radiological lesions were completely resolved after antituberculosis therapy. It is important to consider disseminated tuberculosis for the etiology of FUO inpatient with AML who had suffered from long standing fever.
Adult ; Biopsy ; Bone Marrow ; Brain ; Diagnosis ; Fever ; Fever of Unknown Origin ; Humans ; Hydrocephalus ; Induction Chemotherapy ; Inpatients ; Leukemia ; Leukemia, Myeloid, Acute* ; Lymph Nodes ; Lymphatic Diseases ; Male ; Meningitis ; Tomography, X-Ray Computed ; Tuberculosis* ; Tuberculosis, Meningeal*