Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

Background: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. Methods: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. Results: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised.The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients).Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. Conclusion ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.

Background: and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). Methods: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. Results: The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. Conclusions IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Background: This study aimed to evaluate the association between complementary and alternative medicine (CAM) use and fear of cancer recurrence (FCR) among breast cancer survivors, using a validated multidimensional FCR-assessing instrument. Despite the debate over its medical effects, the use of CAM in breast cancer survivors is increasing. Methods: We recruited 326 breast cancer survivors who had completed the primary cancer treatment. Information on CAM use was obtained using a self-administered questionnaire, and FCR was assessed using the Korean version of the FCR Inventory (FCRI). Multivariate linear regression analysis was performed to evaluate the association between CAM use and FCR. Results: CAM users had higher total FCR scores than CAM non-users after covariate adjustment (CAM users: 74.6 vs. CAM non-users: 68.7; P=0.047). Among the FCRI subscales, CAM users showed higher coping strategy scores (CAM users: 22.3 vs. CAM non-users: 20.6; P=0.034) in the multivariable adjusted analysis. The use of multiple types of CAM was associated with increased FCR in a dose-dependent manner (P=0.002). Conclusion Breast cancer survivors who used CAM had a higher FCR than CAM non-users. The dose-response relationship between the use of multiple types of CAM and FCR suggests that breast cancer survivors who use multiple types of CAM should be provided with appropriate psychological interventions to decrease FCR.

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes.MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes.MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

Ozone is known to cause bronchial inflammation and airway hyper-responsiveness via oxidative injury and inflammation. While other ambient air pollutants such as particulate matter (PM) and nitrogen dioxide showed decreasing trends in mean annual concentrations, ozone concentrations have not declined recently in most countries across the world. Short-term exposure to high concentrations of ozone has been associated with increased mortality and cardiovascular and respiratory morbidity in many regions of the world. However, the long-term effects of ozone have been less investigated than the short-term exposure due to the difficulty in modeling ozone exposure and linking between individual exposures and health outcome data. A recently developed model of ozone exposure enabled the investigation of long-term ozone effects on health outcomes. Recent findings suggested that long-term exposure to ozone was associated with an increased risk of cardiovascular and respiratory mortality. Longitudinal studies using large cohorts also revealed that long-term exposure to ozone was associated with a greater decline in lung function and the progression of emphysema. The development of long-term standards for ozone as well as PM should be considered to protect the respiratory health of the general population and people with chronic respiratory diseases.

Purpose: We aimed to evaluate the clinical features of adolescents who visit emergency departments (EDs) with chest discomfort, and analyze the implications of underlying medical conditions for the development of cardiogenic chest discomfort. Methods: We reviewed the medical records of adolescents (13-18 years) with chest discomfort who visited a tertiary hospital ED in Seoul, Korea from 2014 through 2018. Sex, age, duration and character of the discomfort, symptoms and signs, ED length of stay, abnormal findings of vital signs, chest radiograph, electrocardiogram, and elevated concentrations of cardiac enzymes were reviewed. Final diagnosis was based on cardiac evaluations within 1 year after the index visit. Underlying medical conditions were defined as visits to the cardiology, pulmonology or hematology-oncology clinics at least twice in the preceding year. Initial suspicious clinical findings were defined as palpitation, syncope or high blood pressure. Logistic regression was used to identify predictors for cardiac etiology. Results: Of the 231 patients, 43 (18.6%) and 69 (29.9%) had underlying medical conditions and initial suspicious clinical findings, respectively. The predictors for cardiac etiology were underlying medical conditions (odds ratio, 4.28; 95% confidence interval, 1.09-16.73), initial suspicious clinical findings (4.77; 1.36-16.77), abnormal electrocardiogram (11.54; 3.22-41.32), and elevated concentration of troponin I (66.52; 5.37-823.55). The patients with cardiogenic chest discomfort had a longer median ED length of stay (281.0 minutes [interquartile range, 215.5-369.0] vs. 199.5 [132.8-298.0]; P = 0.004) and a higher hospitalization rate (48.3% vs. 13.4%; P < 0.001) than those with non-cardiogenic chest discomfort. Conclusion It may be necessary to recognize underlying medical conditions and initial suspicious clinical findings in EDs prior to cardiac evaluation in adolescents with chest discomfort.

Ozone is known to cause bronchial inflammation and airway hyper-responsiveness via oxidative injury and inflammation. While other ambient air pollutants such as particulate matter (PM) and nitrogen dioxide showed decreasing trends in mean annual concentrations, ozone concentrations have not declined recently in most countries across the world. Short-term exposure to high concentrations of ozone has been associated with increased mortality and cardiovascular and respiratory morbidity in many regions of the world. However, the long-term effects of ozone have been less investigated than the short-term exposure due to the difficulty in modeling ozone exposure and linking between individual exposures and health outcome data. A recently developed model of ozone exposure enabled the investigation of long-term ozone effects on health outcomes. Recent findings suggested that long-term exposure to ozone was associated with an increased risk of cardiovascular and respiratory mortality. Longitudinal studies using large cohorts also revealed that long-term exposure to ozone was associated with a greater decline in lung function and the progression of emphysema. The development of long-term standards for ozone as well as PM should be considered to protect the respiratory health of the general population and people with chronic respiratory diseases.