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Background: Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases.Methods: Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test.Results: Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66–1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed.Conclusion: Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

We developed a tool to guide decision-making for early triage of COVID-19 patients based on a predicted prognosis, using a Korean national cohort of 5,596 patients, and validated the developed tool with an external cohort of 445 patients treated in a single institution. Predictors chosen for our model were older age, male sex, subjective fever, dyspnea, altered consciousness, temperature ≥ 37.5 °C, heart rate ≥ 100 bpm, systolic blood pressure ≥ 160 mmHg, diabetes mellitus, heart disease, chronic kidney disease, cancer, dementia, anemia, leukocytosis, lymphocytopenia, and thrombocytopenia. In the external validation, when age, sex, symptoms, and underlying disease were used as predictors, the AUC used as an evaluation metric for our model’s performance was 0.850 in predicting whether a patient will require at least oxygen therapy and 0.833 in predicting whether a patient will need critical care or die from COVID-19. The AUCs improved to 0.871 and 0.864, respectively, when additional information on vital signs and blood test results were also used. In contrast, the protocols currently recommended in Korea showed AUCs less than 0.75. An application for calculating the prognostic score in COVID-19 patients based on the results of this study is presented on our website (https://nhimc.shinyapps.io/ih-psc/), where the results of the validation ongoing in our institution are periodically updated.

Background Political change regarding for exemption of co-payment for tuberculosis (TB) treatment was made in July 2016. We investigated the effect of the co-payment waiver on long-term treatment interruption and clinical outcomes among pulmonary TB patients in South Korea. Methods Patients who had newly treated TB in South Korea from 2013–2019 were selected from nationwide data using the entire Korean National Health Insurance Service population. Interrupted time series analysis was used to evaluate the effect of policy implementation on treatment adherence. Moreover, mortality rates were assessed depending on the history of long-term treatment interruption. Results A total of 73,116 and 1,673 patients were included in the final study population for each drug-susceptible and drug-resistant pulmonary TB. After implementing the cost exemption policy, the long-term treatment discontinuation rates tended to decrease in the continuation phase in the drug-susceptible TB group (slope change: −0.097, P = 0.011). However, it was increased in the intensive phase in the drug-resistant TB group (slope change: 0.733, P = 0.001). Drug-resistant TB patients were likely to experience long-term discontinuation of TB treatment (adjusted odds ratio, 6.04; 95% confidence interval [CI], 5.43–6.71), and history of long-term treatment interruption was a significant risk factor for both 1-year and overall mortality rates among the study population (adjusted hazard ratios: 2.01, 95% CI, 1.86–2.18 and 1.77, 95% CI, 1.70–1.84, respectively). Conclusions Implementing the cost exemption policy effectively reduced the long-term treatment discontinuation rate among pulmonary TB patients. Because long-term treatment interruption is relevant to increasing mortalities, political change for widening the coverage helped improve treatment outcomes in TB patients.

OBJECTIVES: Research is lacking on the impacts of exposure to particulate matter (PM) and air pollution on patients with chronic obstructive pulmonary disease (COPD) or asthma. Therefore, we investigate the effects of various air pollution factors on hospitalization for asthma and COPD. METHODS: We obtained data on pollutants—PM(10), PM(2.5), carbon monoxide (CO), ozone (O(3)), nitrogen dioxide (NO(2)), and sulfur dioxide (SO(2))—in Gyeonggi-do, South Korea. We also extracted data from Korean National Health Insurance records and investigated asthma and COPD attacks that required hospitalization from January 2007 through February 2018. We used generalized additive models with Poisson distribution and log transformation to calculate adjusted risk. A time-stratified case-crossover design was used, and conditional logistic regression was performed to analyze these data. RESULTS: Per-unit increases in concentrations of PM(10), PM(2.5), SO(2), NO(2), CO, and O(3) on different best lag days were associated with increased risks for hospital admission for COPD and asthma. SO(2) had the strongest effect on hospital admission for asthma (odds ratio [OR], 1.535; 95 % confidence interval [CI], 1.450–1.619). SO(2) also had the strongest effect on hospital admission for COPD (OR, 1.659; 95 % CI, 1.541–1.786). Subgroup analyses showed that these relationships were stronger in seniors (≥ 65 years old) and women with asthma than in men and nonseniors with COPD. CONCLUSIONS: Short-term exposure to PM(10), PM(2.5), CO, O(3), NO(2), and SO(2) may result in hospitalization for asthma and COPD. Of these pollutants, SO(2) has the strongest effects. Therefore, patients with COPD and asthma should be cautioned against performing outdoor activities when SO(2) levels are high.

BACKGROUND Depression is a common comorbidity among people with chronic obstructive pulmonary disease (COPD), but the health effects of depression in this group of patients remain poorly understood. The purpose of the present study was to investigate the association between COPD and depression, and the effects of comorbid COPD and depression on health care utilization. METHODS Our study sample included 10,180 Korean adults (4,437 men and 5,743 women; all aged ≥ 45 years) who participated in the cross-sectional Korean Longitudinal Study of Aging (KLoSA). The participants were required to self-report any previous diagnosis of COPD. Depression was assessed with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D10). Health care utilization was defined as multiple physician visits (≥6) and multiple hospital admissions (≥2) in the previous year. RESULTS Participants with COPD had a higher prevalence of depression than those without COPD (16.8% vs. 38.1%, respectively; P < 0.001). After adjustment for covariates, participants with COPD had a significantly higher likelihood of multiple physician visits (odds ratio [OR], 95% confidence interval [CI], 1.80 [1.26-2.58]) and multiple hospital admissions (OR [95% CI], 1.62 [1.04-3.51]), while those with COPD plus depression had a higher likelihood of multiple hospital admissions (OR [95% CI], 2.71 [2.34-5.48]). CONCLUSIONS We found a positive association between COPD and depression. Depression in patients with COPD is associated with an increased likelihood of multiple hospital admissions.

Introduction It is unclear whether smokers are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate the association between smoking and the risk of SARS-CoV-2 infection. Methods A matched case–control study was conducted using a large nationwide database. The case group included patients with SARS-CoV-2 infection confirmed by the Korea Centers for Disease Control and Prevention, and the control group was randomly sampled from the general Korean population in the National Health Insurance Service database by matching sex, age, and region of residence. Conditional logistic regression models were used to investigate whether the risk of infection with SARS-CoV-2 was affected by smoking status. Results A total of 4167 patients with SARS-CoV-2 infection and 20 937 matched controls were enrolled. The proportion of ex-smokers and current smokers was 26.6% of the total participants. In multivariate analysis, smoking was not associated with an increased risk of SARS-CoV-2 infection (odds ratio [OR] = 0.56, confidence interval [CI] = 0.50–0.62). When ex-smokers and current smokers were analyzed separately, similar results were obtained (current smoker OR = 0.33, CI = 0.28–0.38; ex-smoker OR = 0.81, CI = 0.72–0.91). Conclusions This study showed that smoking may not be associated with an increased risk of SARS-CoV-2 infection. Smoking tends to lower the risk of SARS-CoV-2 infection; however, these findings should be interpreted with caution. Implications It is unclear whether smokers are more vulnerable to coronavirus disease 2019. In this large nationwide study in South Korea, smoking tended to lower the risk of infection with severe acute respiratory syndrome coronavirus 2. However, these findings should be interpreted with caution, and further confirmatory studies are required.

The severity of the coronavirus disease (COVID-19) is associated with various comorbidities. However, no studies have yet demonstrated the potential risk of respiratory failure and mortality in COVID-19 patients with pre-existing asthma. We selected 7272 adult COVID-19 patients from the Korean Health Insurance Review and Assessment COVID-19 database for this nationwide retrospective cohort study. Among these, 686 patients with asthma were assessed by their severities and evaluated by the clinical outcome of COVID-19 compared to patients without asthma. Of 7272 adult COVID-19 patients, 686 with asthma and 6586 without asthma were compared. Asthma was not a significant risk factor for respiratory failure or mortality among all COVID-19 patients (odds ratio [OR] = 0.99, P = 0.997 and OR = 1.06, P = 0.759) after adjusting for age, sex, and the Charlson comorbidity score. However, a history of acute exacerbation (OR = 2.63, P = 0.043) was significant risk factors for death among COVID-19 patients with asthma. Asthma is not a risk factor for poor prognosis of COVID-19. However, asthma patients who had any experience of acute exacerbation in the previous year before COVID-19 showed higher COVID-19-related mortality, especially in case of old age and male sex.

Objective The aim of this study was to determine the effect of insertion torque and angulation on the push-out strength of screws in Atraumatic Rigid Fixation (ARIX) system. Materials and Methods In vitro mechanical tests of the ARIX system were conducted. Screw plate constructs (n = 120) were tested using five different insertion torques at four different angles relative to the perpendicular axis of the plate. Before the push-out test, screws were locked into the plates, and the push-out force of the screw was measured by applying a load parallel to the screw axis. Results Implant failure was observed at 0.8 Nm at an insertion angle of 15 degrees, and at 1 Nm at 0 degree, 5 degrees and 10 degrees. Two types of failures were observed: cold welding and plate deformation. An insertion torque of 0.8 Nm produced a significantly higher push-out force compared with 0.2 Nm. Non-angled specimens with 0.8 Nm insertion torque exhibited significantly higher screw push-out forces compared with other tested specimens and insertion angles. Insertion angle did not affect screw push-out force at insertion torques of 0, 0.2, 0.4 and 0.6 Nm. Conclusion The ARIX locking system is much more sensitive to insertion torque than angle. An effect of insertion angle was observed only at an insertion torque of 0.8 Nm, under which all angles significantly decreased push-out force relative to zero degrees of angulation. In addition, low insertion torques can result in screws loosening over time, while greater insertion torques than 1 Nm can result in screw head stripping and plate hole deformation.

BACKGROUND Although the use of radial endobronchial ultrasound (R-EBUS) with a guide sheath has shown improved diagnostic capability in peripheral pulmonary lesions, its utility is still low due to variable performance. To overcome its limitation, we evaluated the feasibility and efficacy of R-EBUS combined with transbronchial biopsy (TBB) under fluoroscopic guidance. METHODS We retrospectively reviewed medical records of 74 patients with non-small cell lung cancer (NSCLC) who underwent R-EBUS combined with TBB or TBB alone as a diagnostic technique. Subjects were grouped according to the diagnostic modality used (R-EBUS combined with TBB vs. TBB alone). Each group was matched for age, sex, and location of the biopsy. The chi-square test and paired t-test were used to compare characteristics and identify factors that affected the diagnostic yield. RESULTS The mean age of the study cohort was 67.4 ± 12.8 years, with 21 (56.8%) men and 16 (43.2%) women in each group. The lesion size was significantly smaller in the R-EBUS group (23.6 vs. 33.9, P

Cotton fabrics exhibiting superhydrophobic and antibacterial properties were prepared through sonochemical coating technique. Substantial amount of copper nanoparticles (Cu-NPs) could be deposited on the cotton fabric through sonochemical process using ultrasonic irradiation in water. The effects of Cu-NPs concentration, sonication time and NaOH concentration on the Cu-NPs coating behavior were investigated by FE-SEM observation, EDS elemental analysis and contact angle measurement. Regarding the media for the sonochemical process, alkaline solution was more effective than distilled water due to mercerization effect to make cotton swelled and soft. It was also found that Lotus effect (superhydrophobicity) could be successfully introduced to the hydrophilic cotton fabrics ascribed to micro- and nano-bumps formed by Cu-NPs. The maximum contact angle obtained in the study was 145 degree for the sample coated at 20 mM Cu-NPs and 15 wt% NaOH, respectively. Moreover, antibacterial properties could be added to the fabric by coating of Cu-NPs without further treatment.

Background Flavonoids are natural polyphenols found widely in citrus fruit and peel that possess anti-adipogenic effects. On the other hand, the detailed mechanisms for the anti-adipogenic effects of flavonoids are unclear. Objectives The present study observed the anti-adipogenic effects of five major citrus flavonoids, including hesperidin (HES), narirutin (NAR), nobiletin (NOB), sinensetin (SIN), and tangeretin (TAN), on AMP-activated protein kinase (AMPK) activation in palmitate (PA)-treated HepG2 cells. Methods The intracellular lipid accumulation and triglyceride (TG) contents were quantified by Oil-red O staining and TG assay, respectively. The glucose uptake was assessed using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay. The levels of AMPK, acetyl-CoA carboxylase (ACC), and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and levels of sterol regulatory element-binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression were analyzed by Western blot analysis. The potential interaction between the flavonoids and the γ-subunit of AMPK was investigated by molecular docking analysis. Results The flavonoid treatment reduced both intracellular lipid accumulation and TG content in PA-treated HepG2 cells significantly. In addition, the flavonoids showed increased 2-NBDG uptake in an insulin-independent manner in PA-treated HepG2 cells. The flavonoids increased the AMPK, ACC, and GSK3β phosphorylation levels and decreased the SREBP-2 and HMGCR expression levels in PA-treated HepG2 cells. Molecular docking analysis showed that the flavonoids bind to the CBS domains in the regulatory γ-subunit of AMPK with high binding affinities and could serve as potential AMPK activators. Conclusion The overall results suggest that the anti-adipogenic effect of flavonoids on PA-treated HepG2 cells results from the activation of AMPK by flavonoids.

The present study examined the relationship between the anti-diabetic effect of hesperidin (HES) and the differential gene expression in HES treated high fat diet (HFD)-induced obese mice. Based on the glucose uptake assay, the treatment of HES restored the glucose uptake to control level in an insulin-independent manner in PA-treated HepG2 cells. Western blot analysis confirmed that the treatment of HES increased the insulin-stimulated phosphorylation of Akt and GSK3β in insulin-resistant PA-treated HepG2 cells. HFD-induced obese mice treated with HES significantly reduced serum insulin, blood glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) values. In addition, both glucose tolerance and insulin tolerance were significantly improved to normal level by HES in HFD-induced obese mice. RNA sequencing analysis disclosed that the expression levels of up-regulated 12 genes and down-regulated 6 genes related to insulin signaling and glucose metabolism were restored to normal level by HES in the liver of HFD-induced obese mice. A protein-protein interaction (PPI) network was constructed via search tool for the retrieval of interacting genes/proteins (STRING) analysis, and Eno1, Pik3cd, Hk2, Trib3, Myc, Nos3, Ppargc1a, and Igf2 were located in the functional hubs of the PPI network of glucose metabolism. Furthermore, Western blot analysis confirmed that HES improved insulin sensitivity and glucose homeostasis by normalizing the expression levels of hexokinase-II, enolase-1, and PI3 kinase p110δ to normal level. The overall results suggest that HES possess a potential anti-diabetic effect by normalizing the expression levels of the insulin signaling and glucose metabolism related genes which were perturbed in the liver of HFD-induced obese mice.

We explored the relationship between asthma and early menarche in a representative sample of Korean adolescents.Web-based self-reported data collected from 2006 to 2015 by the Korean Youth Risk Behavior Web-based Survey were used. Menarche status was divided into "early" (12 years of age, n = 69,520) and "not early" (≥12 years of age, n = 234,065).Adolescent girls with early menarche exhibited a higher incidence of asthma (8.1% vs 7.4%, P .001), more frequent school absences because of asthma (10.8% vs 8.7%), and more frequent ≤4-day stretches of school absence (4.6% vs 2.4%) compared with girls with "not early" menarche (all P .001). Multivariate analysis performed after adjusting for multiple confounders revealed a 1.04-fold (95% confidence interval [CI] 1.00-1.07) greater likelihood of asthma in the early menarche than not early menarche group. In addition, the odds ratios for missing school due to asthma for 1 to 3 and ≥4 days per year in the early menarche group were 1.00 (95% CI 1.00-1.02) and 1.21 (95% CI 1.01-1.46), respectively.Adolescents with early menarche exhibited increased incidences of asthma and severe asthma.

A liver mass was incidentally revealed in a 10-year-old male neutered Himalayan cat on radiographic examination conducted in a local animal hospital. The abdominal distention had worsened over the past five months, along with intermittent vomiting and nausea for two weeks. Serum chemistry was unremarkable, except for elevated alkaline phosphatase and gamma-glutamyl transferase levels. Radiography revealed a round-shaped soft mass in the cranial abdomen. Abdominal ultrasonography showed a well defined, massive, fluid-filled cyst with multiple lobes, and heterogeneous echogenicity in the pancreas. Computed tomography examination revealed hypoplasia of the left lobes of the liver, but the vascular changes and enhancement of the mass were not observed on contrast computed tomography images. The herniation of the abdominal fat through the diaphragm was incidentally observed on sonography and computed tomography scan. The patient was tentatively diagnosed with pancreatic cyst. The laparotomy revealed that the origin was not related to the pancreas, but was suspended from the liver. The mass was multilobular and filled with approximately 120 ml of fluid containing a few white blood cells. The patient recovered from anesthesia, but showed postoperative respiratory depression and died of cardiac arrest 15 hours later. Histopathologically, the mass was definitively diagnosed to be hepatic cellular carcinoma.

Objectives: Weekend oversleep or catch-up sleep is common among adolescents, but relatively few data are available with regard to its effects on asthma. Our aim was to investigate whether weekend o...

Objectives: As the numbers of adolescents with asthma are increasing, appropriate recognition of the importance of body weight is necessary. This study explored body weight misconceptions a...

BACKGROUND: Problematic Internet addiction (IA) has been shown to be associated with a variety of psychological comorbidities, but its relationship with adolescent asthma has not yet been investigated in detail. METHODS: We analyzed 18,473 adolescent patients with physician-diagnosed asthma and 205,069 non-asthmatic adolescent patients from the Korean Youth Risk Behavior Web-based Survey. Socioeconomic factors, health behavior factors, psychological factors, and IA status were assessed using the Korean Internet Addiction Proneness Scale. Multiple logistic regression analysis was performed, with adjustment for multiple cofounders, to explore the association between IA and adolescent asthma. RESULTS: Comparison between the adolescent asthma group and non-adolescent asthma group indicated higher rates of probable IA (13.7% vs. 12.1%, respectively, P

Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19). This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients. A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model. Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively. The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs. 45.2%, P P P = 0.041) and mechanical ventilation (5.7% vs. 2.4%, P = 0.015). Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11–2.93) after adjustment for age, sex, and Charlson Comorbidity Index score. Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care. COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.

Background Early suspicion followed by assessing lung function with spirometry could decrease the underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care. We aimed to develop a nomogram to predict the FEV1/FVC ratio and the presence of COPD. Methods We retrospectively reviewed the data of 4241 adult patients who underwent spirometry between 2013 and 2019. By linear regression analysis, variables associated with FEV1/FVC were identified in the training cohort (n = 2969). Using the variables as predictors, a nomogram was created to predict the FEV1/FVC ratio and validated in the test cohort (n = 1272). Results Older age (β coefficient [95% CI], − 0.153 [− 0.183, − 0.122]), male sex (− 1.904 [− 2.749, − 1.056]), current or past smoking history (− 3.324 [− 4.200, − 2.453]), and the presence of dyspnea (− 2.453 [− 3.612, − 1.291]) or overweight (0.894 [0.191, 1.598]) were significantly associated with the FEV1/FVC ratio. In the final testing, the developed nomogram showed a mean absolute error of 8.2% between the predicted and actual FEV1/FVC ratios. The overall performance was best when FEV1/FVC Conclusion The developed nomogram could be used to identify potential patients at risk of COPD who may need further evaluation, especially in the primary care setting where spirometry is not available.

The present study evaluated the anti-obesity effect of sulforaphane (SFN) and glucoraphanin (GRN) in broccoli leaf extract (BLE) on 3T3-L1 adipocytes and ob/ob mice. Based on Oil Red O staining and triglyceride (TG) assay, SFN and BLE significantly reduced (P < 0.05) both lipid accumulation and TG content in the differentiated 3T3-L1 adipocytes. SFN and BLE increased 2-NBDG uptake by 3T3-L1 adipocytes in a dose-dependent manner. Western blot analysis confirmed that SFN and BLE increased the phosphorylation levels of both AMPK (Thr172) and ACC (Ser79), and reduced the expression of HMGCR in liver and white adipose tissues of ob/ob mice. Histological analysis revealed that SFN and BLE ameliorated hepatic steatosis, and reduced the size of adipocyte in ob/ob mice. Treatment with SFN and BLE significantly reduced (P < 0.05) TG content, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), and glucose in the serum of ob/ob mice. RNA sequencing analysis showed that up- or down-regulation of 32 genes related to lipid metabolism was restored to control level in both SFN and BLE-treated ob/ob mice groups. A protein-protein interaction (PPI) network was constructed via STRING analysis, and Srebf2, Pla2g2c, Elovl5, Plb1, Ctp1a, Lipin1, Fgfr1, and Plcg1 were located in the functional hubs of the PPI network of lipid metabolism. Overall results suggest that the SFN content in BLE exerts a potential anti-obesity effect by normalizing the expression of genes related to lipid metabolism, which are up- or down-regulated in ob/ob mice.

Background Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying their anti-adipogenesis effects is poorly understood. Objectives This study examined the anti-adipogenic effects of naringenin and naringin by determining differential gene expression patterns in these flavonoids-treated 3T3-L1 adipocytes. Methods Lipid accumulation and triglyceride (TG) content were determined by Oil red O staining and TG assay. Glucose uptake was measured using a 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose fluorescent d-glucose analog. The phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl Co-A carboxylase (ACC) were observed via Western blot analysis. Differential gene expressions in 3T3-L1 adipocytes were evaluated via RNA sequencing analysis. Results Naringenin and naringin inhibited both lipid accumulation and TG content, increased phosphorylation levels of both AMPK and ACC and decreased the expression level of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in 3T3-L1 adipocytes. RNA sequencing analysis revealed that 32 up-regulated (> 2-fold) and 17 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Scd1, Mogat1, Dgat, Lipin1, Cpt1a, and Lepr, were normalized to the control level in naringenin-treated adipocytes. In addition, 25 up-regulated (> 2-fold) and 25 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Fabp5, Scd1, Srebf1, Hmgcs1, Cpt1c, Lepr, and Lrp1, were normalized to the control level by naringin. Conclusions The results indicate that naringenin and naringin have anti-adipogenic potentials that are achieved by normalizing the expression levels of lipid metabolism-related genes that were perturbed in differentiated 3T3-L1 cells.

Background Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further. Objective This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells. Methods Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK. Results The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Conclusions The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.

BACKGROUND In the era of artificial intelligence, event prediction models are abundant. However, considering the limitation of the electronic medical record–based model, including the temporally skewed prediction and the record itself, these models could be delayed or could yield errors. OBJECTIVE In this study, we aim to develop multiple event prediction models in intensive care units to overcome their temporal skewness and evaluate their robustness against delayed and erroneous input. METHODS A total of 21,738 patients were included in the development cohort. Three events—death, sepsis, and acute kidney injury—were predicted. To overcome the temporal skewness, we developed three models for each event, which predicted the events in advance of three prespecified timepoints. Additionally, to evaluate the robustness against input error and delays, we added simulated errors and delayed input and calculated changes in the area under the receiver operating characteristic curve (AUROC) values. RESULTS Most of the AUROC and area under the precision-recall curve values of each model were higher than those of the conventional scores, as well as other machine learning models previously used. In the error input experiment, except for our proposed model, an increase in the noise added to the model lowered the resulting AUROC value. However, the delayed input did not show the performance decreased in this experiment. CONCLUSIONS For a prediction model that was applicable in the real world, we considered not only performance but also temporal skewness, delayed input, and input error.

Background: Early suspicion followed by assessing lung function with spirometry could decrease the underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care. We aimed to develop a nomogram to predict the FEV1/FVC ratio and the presence of COPD.Methods: We retrospectively reviewed data of 4,241 adult patients who underwent spirometry between 2013 and 2019. By linear regression analysis, variables associated with FEV1/FVC were identified in the training cohort (n=2,969). Using the variables as predictors, a nomogram was created to predict the FEV1/FVC ratio and validated in the test cohort (n=1,272).Results: Older age (Odds ratio [OR], 0.858; 95% confidence interval [CI], 0.833-0.885), male sex (OR, 0.149; 95% CI, 0.064–0.348), current or past smoking history (OR, 0.036; 95% CI, 0.015–0.086), the presence of dyspnea (OR, 0.086; 95% CI, 0.027–0.275), and the absence of overweight (OR, 2.445; 95% CI, 1.210–4.942) were significantly associated with the FEV1/FVC ratio. In the final testing, the developed nomogram showed a mean absolute error of 0.822 (95% CI, 0.789–0.854) between the predicted and actual FEV1/FVC ratios. The overall performance was best when FEV1/FVC < 70% was used as a diagnostic criterion for COPD; the sensitivity, specificity, and balanced accuracy were 82.3%, 68.6%, and 75.5%, respectively.Conclusion: The developed nomogram could be used to identify potential patients at risk of COPD who may need further evaluation, especially in the primary care setting where spirometry is not available.

BACKGROUND Sulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood. OBJECTIVES This study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice. METHODS Nitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice. RESULTS The SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a "functional cluster" in the middle of the network. CONCLUSIONS The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.

Background Inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, but its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not known. This study aimed to investigate the association between ICS use and the risk of SARS-CoV-2 infection among the patients with chronic respiratory diseases. Methods The Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea provided nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15. The risks of SARS-CoV-2 infection were retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test. Results Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among the types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. The multivariate analysis showed no significant increase in infection with ICS use (OR, 0.84; 95% CI, 0.66–1.03). Moreover, there were no associations between the risk of infection, and doses or types of ICS prescribed. Conclusion Prior ICS use did not increase the risk of SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect the risk. This study supports the current guidelines to manage patients taking ICS during the SARS-CoV-2 pandemic.

As patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) often present coagulopathy depending on disease severity, appropriate prevention and treatment for hemodynamics control are most essential for Coronavirus disease 2019 (COVID‐19) management (Helms, et al 2020). Although several papers alarmed the decrease of blood donation in the COVID‐19 pandemic as expected (Mohammadi, et al 2020, Pagano, et al 2020), few research investigated the actual prevalence of blood transfusion requested in hospitalized COVID‐19 patients (Berzuini, et al 2020, Doyle, et al 2020), and no publication reported nationwide result until today. Here, we examined the transfusion demand in COVID‐19 patients using the Korean nationwide COVID‐19 patient database generated by the government.

Despite the rapid increase in electronic cigarette (e-cigarette) smoking, little is known about the factors associated with their use, particularly in adolescents with asthma. Our study investigated the prevalence of, and factors associated with asthma.We analyzed data from the Korean Youth Risk Behavior Web-based Survey of 44,479 adolescents with physician-diagnosed asthma and 445,692 subjects without asthma. Sociodemographic factors, psychosocial factors, and e-cigarette smoking patterns were investigated by self-report questionnaires. Multiple logistic regression was used to investigate the factors associated with ever or current e-cigarette risks in adolescents with asthma, with adjustment for confounding factors.Significantly more subjects had a smoking habit in the asthma group than in the non-asthma group. Among the adolescents with asthma, 4,420 (9.9%) smoked e-cigarettes (ever-users), and 1,962 (4.4%) smoked e-cigarettes within the last 30 days (current users). Multiple logistic regression showed that both ever and current e-cigarette use were significantly associated with male gender, higher family income, residence in an urban area, alcohol drinking, substance use experience, sexual experience, and friends' smoking. Current e-cigarette use was also significantly associated with high caffeine intake, no regular exercise, and experience of violence in adolescents with asthma.E-cigarette smoking behavior was significantly more frequent in adolescents with asthma than in those without asthma, and multiple psychosocial factors were associated with e-cigarette smoking. Our results could inform e-smoking control programs and help identify adolescents with asthma at high risk of e-cigarette smoking, to ultimately prevent and reduce this behavior.

Purpose Critical care medicine continues to evolve. However, critical care cases require increasing amount of medical resources. Intensive care unit (ICU) mortality significantly impacts the overall efficiency of healthcare resources within a system of limited medical resources. This study investigated the factors related to ICU mortality using long-term nationwide cohort data in South Korea. Materials and methods This retrospective cohort study used data of 14905721 patients who submitted reimbursement claims to the Korean Health Insurance Service between January 1, 2011 and December 31, 2015. A total of 1498102 patients who were admitted to all ICU types, except neonatal and long-term acute care hospitals, were enrolled. Results Of the total 1498102 participants, 861397 (57.5%) were male and 636705 (42.5%) were female. The mean age at admission was 63.4±18.2 years; most of the subjects were aged over 60 years. During the 5-year period, in-hospital mortality rate was 12.9%. In Cox analysis, both in-hospital and 28-day mortality rates were significantly higher in male patients and those of lower socioeconomic status. As age increased and the number of nursing staff decreased, the mortality risk increased significantly by two or three times. The mortality risk was lower in patients admitted to an ICU of a tertiary university hospital and an ICU where intensivists worked. Conclusion The number of nursing staff and the presence of an intensivist in ICU were associated with the ICU mortality rate. Also, increasing the number of nursing staff and the presence of intensivist might reduce the mortality rate among ICU patients.

Objectives: In the study, we explored whether sleep chronotypes are associated with asthma in adolescents. Methods: We analyzed 24,655 physician-diagnosed adolescent asthmatic patients and 253,775 non-asthmatic adolescent patients from the Korea Youth Risk Behavior Web-based Survey (KYRBWS). Socioeconomic factors, health behaviors factors, psychological factors, and sleep parameters were assessed using the Munich Chronotype Questionnaire (MCTQ). Logistic regression after adjusting for multiple confounders was used to explore the association between sleep chronotype and asthma. Results: The asthmatic adolescent group slept less (&le, 5 h: 24.3% vs. 23.2%) than the non-asthmatic adolescent group. Mean sleep duration (430.6 &plusmn, 95.6 vs. 433.5 &plusmn, 93.6 min), midpoint of sleep on school-free days (MSF, 255.9 &plusmn, 75.9 vs. 258.3 &plusmn, 73.6 min), midpoint of sleep on school days (MSW, 199.1 &plusmn, 49.1 vs. 200.1 &plusmn, 48.4 min), sleep duration on school days (SDW, 398.2 &plusmn, 98.1 vs. 400.2 &plusmn, 96.8 min), and sleep duration on school-free days (SDF, 511.8 &plusmn, 151.9 vs. 516.7 &plusmn, 147.2 min) were significantly lower, sleep satisfaction was significantly poorer (low sleep satisfaction: 41.3% vs. 37.5%), and late chronotype was significantly higher in the asthmatic adolescent (21.1% vs. 20.0%). After adjusting for multiple confounders, late chronotype was significantly associated with an increased frequency of adolescent asthma (OR 1.05, 95% CI 1.01&ndash, 1.09) compared to intermediate chronotypes. Conclusions: Although our study shows a very modest association (OR of 1.05 in the fully adjusted model), we show that the late sleep chronotype is associated with asthma in adolescents in South Korea.

Introduction The prognosis of bronchiectasis is not well known. The purpose of this study was to evaluate the association between body mass index (BMI) and mortality in bronchiectasis using a large nationwide population-based cohort. Material and methods Using the National Health Insurance Service-Health Screening Cohort in Korea, individuals with bronchiectasis were identified from 2004 to 2006 and monitored for up to 10 years. Mortality in bronchiectasis was analyzed based on a BMI score 25.0 kg/m2 (obese). Results A total of 2769 individuals with bronchiectasis were included. The underweight, normal weight, overweight, and obese accounted for 5.1%, 40.4%, 25.4%, and 29.3% of all patients with bronchiectasis, respectively. Compared to normal weight, underweight in bronchiectasis was associated with increased all-cause mortality (hazard ratio [HR] = 2.60; 95% confidence interval [CI] = 1.92–3.54), while obese was associated with decreased all-cause mortality (HR = 0.71; 95% CI = 0.55–0.93). This relationship between BMI and mortality was more prominent in respiratory disease-related mortality. Conclusions BMI is a predictor of mortality in bronchiectasis. Underweight is associated with increased mortality among individuals with bronchiectasis while obese is associated with decreased mortality.

Background: Bronchiectasis is associated with an increased incidence of atherosclerotic cardiovascular disease (ASCaVD) and atherosclerotic cerebrovascular disease (ASCeVD). Its effect on associated mortality is unclear. Objectives: This study investigated the effects of bronchiectasis exacerbation prior to ASCaVD or ASCeVD events on mortality in patients with bronchiectasis using a large population–based database. Methods: A retrospective cohort of patients with bronchiectasis who experienced ASCaVD ( n = 1066) or ASCeVD ( n = 825) was studied for the first time using a nationwide population–based database (National Health Insurance Service-National Sample Cohort, Korea, 2002–2015). We classified each cohort according to the presence of moderate bronchiectasis exacerbation within 1 year before the ASCaVD or ASCeVD event. We evaluated 90-day, 1-year, and all-cause mortalities risk. Results: Within 1 year before the index ASCaVD or ASCeVD event, 149 (13.9%) and 112 (13.6%) patients with bronchiectasis experienced moderate exacerbation(s), respectively. Mild exacerbations did not different in frequency between the survivors and nonsurvivors. In both cohorts, more nonsurvivors experienced moderate exacerbations than survivors. The odds ratios of 90-day and 1-year mortalities and hazard ratios of all-cause mortalities on experiencing moderate exacerbations were 2.27 [95% confidence interval (CI) = 1.26–4.10], 3.30 (95% CI = 2.03–5.38), and 1.78 (95% CI = 1.35–2.34) in the bronchiectasis-ASCaVD cohort and 1.73 (95% CI = 0.94–3.19), 1.79 (95% CI = 1.07–3.00), and 1.47 (95% CI = 1.10–1.95), in the bronchiectasis-ASCeVD cohort. Conclusion: Hospitalization or emergency room visit for bronchiectasis exacerbation within 1 year before ASCaVD or ASCeVD is associated with an increased ASCaVD- or ASCeVD-associated mortality.

An innovative plastic deformation method is proposed to tune metal-based MEMS devices after fabrication. The plastic deformation is a well-known failure mechanism in MEMS devices, which includes a phenomenon that the devices do not return original position after repeated actuation. Here, in contrast to this common experience, we exploit the plastic deformation for the first time to tune the performance of MEMS devices, by producing deliberate, controlled plastic deformation with the help of Joule heating. The proposed plastic deformation method is precisely and predictably controlled by the model we developed here, and it was successfully demonstrated and evaluated using a fabricated MEMS device. Unlike conventional plastic deformation methods, the proposed method was accomplished solely by electrical control, which means that the method can be employed in integrated devices. Tuning resolution was demonstrated at a 10-nm level, which is remarkably smaller than that of conventional plastic deformation methods, where the tuning resolution is typically several micrometers. We confirmed that the proposed method does not deteriorate the basic performance of the fabricated MEMS devices. Finally, we proposed and demonstrated a method for calibrating MEMS devices after fabrication and suggested an interesting application, which is recovering the performance of aged MEMS devices. [2017-0129]