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Recent studies elucidate that coronavirus disease 2019 (COVID‐19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID‐19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population‐based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID‐19 National Health Insurance Service cohort. The Fine and Gray's regression with all‐cause death as a competing event was adopted to evaluate PE and DVT risks after COVID‐19. This study included a total of 1,601,835 COVID‐19 patients and 14,011,285 matched individuals without COVID‐19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67–10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75–5.29; p < 0.001) was higher in COVID‐19 group in individuals without complete COVID‐19 vaccination. In addition, individuals with complete COVID‐19 vaccination still had a higher risk of COVID‐19‐related PE (aHR, 1.48; 95% CI, 1.15–1.88; p < 0.001). However, COVID‐19 was not a significant risk factor for DVT among those with complete COVID‐19 vaccination. COVID‐19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that hearing impairment is associated with the onset of depression. However, large‐scale epidemiological studies are required to define this association more clearly. We aimed to investigate the risk of new‐onset depression in Korean older adults with and without hearing impairment. Methods: From the National Health Insurance Service‐Senior Cohort, which is a retrospective‐prospective hybrid database, we analyzed data for 254,466 older adults enrolled in the Korea National Health Insurance Service‐Senior Cohort who underwent at least one health screening between 2003 and 2019. A Cox proportional hazards regression model was used to evaluate the association between hearing impairment and the risk of incident depression, which was presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CIs). All participants were followed up until the date of incident depression, death, or December 31, 2019. Results: During 3,417,682 person‐years of follow‐up investigation, hearing impairment was associated with a higher risk of incident depression (vs. no hearing impairment) in the final adjusted model (aHR, 1.11; 95% CI, 1.01–1.21; p = 0.033). Stratified analyses revealed a significant interaction among age, hearing impairment, and the risk of depression. Participants aged <65 years had a higher risk of depression (aHR, 1.29; 95% CI, 1.12–1.50; p < 0.001) than those aged 65 or above (aHR, 1.15; 95% CI, 1.01–1.30; p = 0.032). Conclusions: Hearing impairment is independently associated with a higher risk of depression among older adults. The prevention and treatment of hearing impairment may aid in mitigating the risk of incident depression. Level of Evidence: Level 3 Laryngoscope, 133:3144–3151, 2023 [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is considered a major cause of death worldwide, and various studies have been conducted for its early diagnosis. Our work developed a scoring system by predicting and validating COPD and performed predictive model implementations. Participants who underwent a health screening between 2017 and 2020 were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) database. COPD individuals were defined as aged 40 years or older with prebronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC < 0.7). The logistic regression model was performed, and the C-index was used for variable selection. Receiver operating characteristic (ROC) curves with area under the curve (AUC) values were generated for evaluation. Age, sex, waist circumference and diastolic blood pressure were used to predict COPD and to develop a COPD score based on a multivariable model. A simplified model for COPD was validated with an AUC value of 0.780 from the ROC curves. In addition, we evaluated the association of the derived score with cardiovascular disease (CVD). COPD scores showed significant performance in COPD prediction. The developed score also showed a good effect on the diagnostic ability for CVD risk. In the future, studies comparing the diagnostic accuracy of the derived scores with standard diagnostic tests are needed. [ABSTRACT FROM AUTHOR]

The partner switching system (PSS) of the SigF regulatory pathway in Mycobacterium smegmatis has been previously demonstrated to include the anti-sigma factor RsbW (MSMEG_1803) and two anti-sigma factor antagonists RsfA and RsfB. In this study, we further characterized two additional RsbW homologs and revealed the distinct roles of three RsbW homologs [RsbW1 (MSMEG_1803), RsbW2 (MSMEG_6129), and RsbW3 (MSMEG_1787)] in the SigF PSS. RsbW1 and RsbW2 serve as the anti-sigma factor of SigF and the protein kinase phosphorylating RsfB, respectively, while RsbW3 functions as an anti-SigF antagonist through its protein interaction with RsbW1. Using relevant mutant strains, RsfB was demonstrated to be the major anti-SigF antagonist in M. smegmatis. The phosphorylation state of Ser-63 was shown to determine the functionality of RsfB as an anti-SigF antagonist. RsbW2 was demonstrated to be the only protein kinase that phosphorylates RsfB in M. smegmatis. Phosphorylation of Ser-63 inactivates RsfB to render it unable to interact with RsbW1. Our comparative RNA sequencing analysis of the wild-type strain of M. smegmatis and its isogenic Δ aa 3 mutant strain lacking the aa 3 cytochrome c oxidase of the respiratory electron transport chain revealed that expression of the SigF regulon is strongly induced under respiration-inhibitory conditions in an RsfB-dependent way. [ABSTRACT FROM AUTHOR]

Therapeutic ineffectiveness involves drug-related therapeutic failure, inefficacy or resistance and has not been sufficiently studied. Objective of our study was to evaluate reporting trends in therapeutic ineffectiveness by year and describe factors affecting therapeutic ineffectiveness using the Korea Adverse Event Reporting System. Proportion of therapeutic ineffectiveness reports was based on total submitted reports between 2000 and 2016. Utilizing 2016 alone, we compared the characteristics of therapeutic ineffectiveness with age group and gender matching by random extraction. We conducted a logistic regression analysis to estimate reporting odds ratios (ROR) and its 95% confidence intervals (CI) for reports by type of reporters, e.g., doctors, pharmacists, or consumers. We presented most frequent reports by the anatomical main groups and therapeutic subgroups according to the Anatomical Therapeutic Chemical (ATC) classification system. For the 17-years, the proportion of therapeutic ineffectiveness adverse drug reactions reporting ranged from 0.0% to 3.7% between 2000 and 2016. Of 228,939 reports, 2,797 (1.2%) were submitted in 2016. Consumers accounted for 6.92% of reports and doctors accounted for 45.49%, in which, consumers were more likely to report therapeutic ineffectiveness than doctors (adjusted ROR 3.98; 95% CI, 2.92 to 5.41). According to the ATC classification system, “nervous system” was the most frequently reported anatomical group (18.7%) and “parathyroid hormones and analogues” was reported most frequently in the pharmacological subgroup (23.7%). Teriparatide, a drug used to treat osteoporosis, had the most reports (11.0%). Therapeutic ineffectiveness reports may be used as a scientific tool for the reevaluation of respective drugs in order to confirm of its therapeutic effects. [ABSTRACT FROM AUTHOR]

The differential pattern and characteristics of completeness in adverse event (AE) reports generated by hospitals/clinics, pharmacies, consumer and pharmaceutical companies remain unknown. Thus, we identified the characteristics of complete AE reports, compared with those of incomplete AE reports, using a completeness score. We used Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) between January 1, 2016 and December 31, 2016. The completeness score was determined out of a total of 100 points, based on the presence of information on temporal relationships, age and sex of patients, AE progress, name of reported medication, reporting group by profession, causality assessment, and informational text. AE reports were organized into four groups based on affiliation: hospitals/clinics, pharmacies, consumers, and pharmaceutical companies. Affiliations that had median completeness scores greater than 80 points were classified as ‘well-documented’ and these reports were further analyzed by logistic regression to estimate the adjusted odds ratios and 95% confidence intervals. We examined 228,848 individual reports and 735,745 drug-AE combinations. The median values of the completeness scores were the highest for hospitals/clinics (95 points), followed by those for consumers (85), pharmacies (75), and manufacturers (72). Reports with causality assessment of ‘certain’, ‘probable’, or ‘possible’ were more likely to be ‘well-documented’ than reports that had causality assessments of ‘unlikely’. Serious reports of AEs were positively associated with ‘well-documented’ reports and negatively associated with hospitals/clinics. [ABSTRACT FROM AUTHOR]

Air pollution and meteorological factors can exacerbate susceptibility to respiratory viral infections. To establish appropriate prevention and intervention strategies, it is important to determine whether these factors affect the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this study examined the effects of sunshine, temperature, wind, and air pollutants including sulfur dioxide (SO 2), carbon monoxide (CO), ozone (O 3), nitrogen dioxide (NO 2), particulate matter ≤2.5 μm (PM 2.5), and particulate matter ≤10 μm (PM 10) on the age-standardized incidence ratio of coronavirus disease (COVID-19) in South Korea between January 2020 and April 2020. Propensity score weighting was used to randomly select observations into groups according to whether the case was cluster-related, to reduce selection bias. Multivariable logistic regression analyses were used to identify factors associated with COVID-19 incidence. Age 60 years or over (odds ratio [OR], 1.29; 95% CI, 1.24–1.35), exposure to ambient air pollutants, especially SO 2 (OR, 5.19; 95% CI, 1.13–23.9) and CO (OR, 1.17; 95% CI, 1.07–1.27), and non-cluster infection (OR, 1.28; 95% CI, 1.24–1.32) were associated with SARS-CoV-2 infection. To manage and control COVID-19 effectively, further studies are warranted to confirm these findings and to develop appropriate guidelines to minimize SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]

In this study, analysis of sensing signal profiles was conducted focusing on the close relationship between electrical conductivity and signal intensity in surface treated poly(dimethylsiloxane)/carbon nanotube (PDMS/CNT) composite patches for the purpose of their practical application as flexible chemical sensors. The flexible PDMS/CNT composite patches were prepared from a PDMS/CNT mixture with a two-roll apparatus. It was found that the PDMS/CNT pads showed a high electrical conductivity (10−1 S/m) even at low CNT loading (0.6 wt %) and a contact angle range of 105–118°. The surface of the obtained PDMS/CNT composite patches was treated using a simple bio-conjugation method to incorporate beta-cyclodextrin (beta-CD) molecules onto the surface as a sensing medium, in order to detect a model compound (Methyl Paraben, MePRB). FT-IR spectra indicated that beta-cyclodextrin molecules were effectively introduced on the surface of the PDMS/CNT patches. It was shown that the sensor signal intensity was substantially dependent on the base current value, which increased with increasing CNT loading. Accordingly, the base current value was intimately associated with the electrical conductivity of the composite patches. On the other hand, the increase in current over the base current (ΔI/I0) obtained after the addition of the model compound was inversely proportional to the CNT content. In this way, analysis on the sensing signal profiles of the flexible chemical sensor system was conducted to determine a process window. This study is a very useful springboard for future research activities, as more profound studies are necessary to fully understand sensing signal profiles. [ABSTRACT FROM AUTHOR]

Background: Exercise is an important method to control the progression of diabetes. Since diabetes compromises immune function and increases the risk of infectious diseases, we hypothesized that exercise may affect the risk of infection by its immunoprotective effects. However, population-based cohort studies regarding the association between exercise and the risk of infection are limited, especially regarding changes in exercise frequency. The aim of this study was to determine the association between the change in exercise frequency and the risk of infection among patients with newly diagnosed diabetes., Methods: Data of 10,023 patients with newly diagnosed diabetes were extracted from the Korean National Health Insurance Service-Health Screening Cohort. Self-reported questionnaires for moderate-to-vigorous physical activity (MVPA) were used to classify changes in exercise frequency between two consecutive two-year periods of health screenings (2009-2010 and 2011-2012). The association between changes in exercise frequency and the risk of infection was evaluated using multivariable Cox proportional-hazards regression., Results: Compared with engaging in ≥ 5 times of MVPA/week during both periods, a radical decrease in MVPA (from ≥ 5 times of MVPA/week to physical inactivity) was associated with a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.03-2.48) and upper respiratory tract infection (aHR, 1.15; 95% CI, 1.01-1.31). In addition, a reduction of MVPA from ≥ 5 to < 5 times of MVPA/week was associated with a higher risk of pneumonia (aHR, 1.52; 95% CI, 1.02-2.27), whereas the risk of upper respiratory tract infection was not higher., Conclusion: Among patients with newly diagnosed diabetes, a reduction in exercise frequency was related to an increase in the risk of pneumonia. For patients with diabetes, a modest level of physical activity may need to be maintained to reduce the risk of pneumonia., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Prediction of type 2 diabetes mellitus (DM) has been studied widely. However, a hospital visit was necessary to apply previous prediction models for the evaluation of DM. This study was conducted to develop and validate a hospital visit-free self-diagnosis tool for DM., Methods: Participants who underwent health screening between 2017-2018 (n=7,519; training cohort) and 2019-2020 (n=7,564; validation cohort) were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES). DM was defined as doctor-diagnosed DM in a questionnaire. Logistic regression was used to determine independent predictors for DM, and a multivariable logistic regression-based nomogram was developed for the prediction of DM, which was validated in a cohort consisting of an independent population. The presence of nonalcoholic fatty liver disease (NAFLD) was operationally defined using the KNHANES-NAFLD score., Results: Age, sex, waist circumference, systolic blood pressure, total cholesterol, triglyceride, aspartate aminotransferase, blood urea nitrogen, urinary protein, urinary glucose, and NAFLD were identified as independent predictors for DM. After excluding laboratory variables that require laboratory tests, a simplified multivariable model was conducted based on hospital visit-free variables, including age, sex, waist circumference, systolic blood pressure, and NAFLD. The full and simplified prediction models for DM were presented as nomograms. In the independent validation cohort, the full and simplified DM prediction models were validated with an area under the curve values of 0.903 and 0.824 from the receiver operating characteristic curves, respectively., Conclusions: Involvement of NAFLD has allowed satisfactory prediction of DM without laboratory tests that require a hospital visit. The developed model may be promising in terms of early diagnosis of DM among individuals without hospital visits and may reduce the socioeconomic burden of DM in the real-world, which awaits future prospective trials to confirm., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2195/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a case/non-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016., Methods: Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI)., Results: Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66-4.38). Higher ROR estimates were shown in female (2.33, 1.48-3.67) and in those with polypharmacy (2.20, 1.35-3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components., Conclusion: These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

This study sought to describe and to evaluate the characteristics of the Health Screening Records Database (HSRD) of the Korea Association of Health Promotion as a data source for epidemiologic studies. The HSRD was compared to a National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) database for 2015. Common variables between the databases were selected, and sex-based analyses were conducted. The HSRD showed statistical concordance when NHIS-HEALS estimates fell within the HSRD estimate's 95% confidence interval. The HSRD and NHIS-HEALS included 946461 and 111690 participants in health screening programs, respectively. Compared to the NHIS-HEALS, the HSRD had more female (55.2% vs. 42.6%) but fewer older adult participants (34.4% vs. 51.2%). Virtually all variables had clinical concordance, with some having statistical concordance as well, among both general and life-transition program participants. The HSRD comprised more clinical information over a wider age range in contrast to the NHIS-HEALS, while showing clinical concordance. Providing more comprehensive clinical data, the HSRD may serve as an alternative resource for epidemiologic studies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Aim: To investigate the effect of methylsulfonylmethane (MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice., Methods: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-ras (G12V), were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot analysis was used to detect caspases, poly (ADP-ribose) polymerase (PARP), and B-cell lymphoma 2 (Bcl-2) expressions. For in vivo study, we administered MSM to H-ras (12V) transgenic mice for 3 mo., Results: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-ras (G12V) cells in a dose-dependent manner. That was correlated with significantly increased apoptosis and reduced cell numbers in MSM treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM; however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was greatly inhibited in the H-ras (12V) transgenic mice treated with MSM, compared to control, by showing reduced tumor size and number. Cleaved PARP was significantly increased in non-tumor treated with MSM compared to control., Conclusion: Liver injury was also significantly attenuated in the mice treated with MSM. Taken together, all the results suggest that MSM has anti-cancer effects through inducing apoptosis in liver cancer.