Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions.Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.

PURPOSE: This prospective clinical study was conducted to evaluate the clinical usefulness of the freely detachable zirconia ball- and spring-retained implant prosthesis (BSRP) through a comparative analysis of screw- and cement-retained implant prosthesis (SCRP). MATERIALS AND METHODS: A multi-center, randomized, prospective clinical study evaluating the clinical usefulness of the detachable zirconia ball- and spring-retained implant prostheses was conducted. Sixty-four implant prostheses in 64 patients were examined. Periodic observational studies were conducted at 0, 3, 6, and 12 months after delivery of the implant prosthesis. Factors such as implant success rate, marginal bone resorption, periodontal pocket depth, plaque and bleeding index, and prosthetic complications were evaluated, respectively. RESULTS: During the 1-year observation period, all implants survived without functional problems and clinical mobility, showing a 100% implant success rate. Marginal bone resorption was significantly higher in the SCRP group than in the BSRP group only at the time of implant prosthesis delivery (P = .043). In all observation periods, periodontal pocket depth was slightly higher in the BSRP group than in the SCRP group, but there was no significant difference (P > .05). The modified plaque index (mPI) scores of both groups were moderate. Higher ratio of a score 2 in modified sulcus bleeding index (mBI) was observed in the BSRP group in the 6- and 12-months observation. CONCLUSION Within the limitations of this study, the newly developed zirconia ball- and spring-retained implant prosthesis could be considered as an applicable and predictable treatment method along with the existing screw- and cement-retained prosthesis.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the right-left arm difference in detection of hypertension in the general Korean population. METHODS: This study analyzed data from the Cardiovascular and Metabolic Disease Etiology Research Center cohort. Study population was 2,103 people who were aged 30 to 64 years old, without history of major cardiovascular diseases, and did not use antihypertensive medication. Brachial blood pressures (BPs) were measured for both arms using an automated oscillometric device equipped with 2 cuffs for simultaneous double-arm measurements. Systolic and diastolic blood pressures (SBP and DBP) were measured 3 times, and the average value was used in the analysis. Overall hypertension was defined as elevated blood pressure (SBP/DBP ≥140/90 mmHg) at the arm with higher value, while right-arm or left-arm hypertension was defined as elevated BP at each arm. Sensitivity was calculated as the number of each-arm hypertension divided by the number of overall hypertension. RESULTS: Overall 8.6% of the population had hypertension at either arm, while 7.8% had right-arm hypertension, 7.2% had left-arm hypertension, and 6.4% had both arms hypertension. The sensitivity for the detection of hypertension was 90.6% when BP was measured only at right arm, and 83.4% when measured only at left arm. Corresponding sensitivity were 87.9% and 87.1% in men, and 95.4% and 76.9% in women. CONCLUSIONS: Single-arm measurements, compared to double-arm measurements, may underestimate the prevalence of hypertension. However, if double-arm measurements are unavailable, right arm is preferred for measurement of BP, especially in women.
Arm ; Asian Continental Ancestry Group ; Blood Pressure ; Cardiovascular Diseases ; Cohort Studies ; Female ; Humans ; Hypertension ; Male ; Metabolic Diseases ; Prevalence

BACKGROUND AND OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of dizziness with a high recurrence rate. This study aimed to analyze the recurrence rate and the risk factors for recurrence using the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC 2002–2013) data. SUBJECTS AND METHOD: Patients aged 20 years or older who were diagnosed with BPPV in the period of 2002–2012 and had at least 1 year of monitoring period were included in this study. The diagnosis of BPPV was made when the code for BPPV (KCD-6 code H811) was used or when canalith reposition therapy (EDI code MX035) was entered even in cases with different diagnoses. The risk factors of BPPV recurrence were analyzed. RESULTS: Of the total of 21355 patients diagnosed with BPPV, 5876 patients (28%) demonstrated recurrence. Multiple recurrences were common. When using the univariate regression analysis, age, sex, vestibular disease, headache, osteoporosis, and ischemic heart disease were found significant. When the patients were classified into 4 groups according to age and sex, vestibular diseases were found as a common risk factor for recurrence in all groups, while headache, osteoporosis, hypertension, and ischemic heart disease were significant in females. CONCLUSION: The recurrence rate of BPPV in the Korean adult population was approximately 28% and recurrences were more common in patients aged over 65 and in females. Patients with vestibular diseases were at a higher risk of recurrence regardless of age or sex, while headache, osteoporosis, hypertension and ischemic heart disease increased the risk of recurrence in females.
Adult ; Benign Paroxysmal Positional Vertigo* ; Cohort Studies ; Diagnosis ; Dizziness ; Female ; Headache ; Humans ; Hypertension ; Methods ; Myocardial Ischemia ; National Health Programs ; Osteoporosis ; Recurrence* ; Risk Factors* ; Vestibular Diseases

Mortalities from cardiovascular disease in Korea have decreased markedly over the past three decades. The major cardiovascular and metabolic risk factors, however, remain prevalent, and their burden on health is large. The Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) planned a cohort study in order to identify novel risk factors and to develop evidence-based prevention strategies of cardiovascular and metabolic diseases. The CMERC deliberately designed two prospective cohorts, a community-based general population cohort (the CMERC cohort) and its sister cohort (a hospital-based high-risk patient cohort), covering a broad spectrum of cardiovascular and metabolic diseases. This paper describes the CMERC cohort study of community-dwelling adults aged 30 to 64 years. A total of 8097 adults completed baseline measurement between 2013 and 2018. Baseline measurements assessed socio-demographic factors, medical history, health-related behaviors, psychological health, social network and support, anthropometry, body composition, and resting blood pressure and comprised electrocardiography, carotid artery ultrasonography, fasting blood analysis, and urinalysis. Both active follow-up through an annual telephone survey and a 5-year on-site health examination survey and passive follow-up through secondary data linkage with national databases, such as national death records, have been applied. Researchers interested in collaborative research may contact the corresponding author.
Adult ; Anthropometry ; Blood Pressure ; Body Composition ; Cardiovascular Diseases ; Carotid Arteries ; Cohort Studies ; Death Certificates ; Electrocardiography ; Fasting ; Follow-Up Studies ; Humans ; Information Storage and Retrieval ; Korea ; Metabolic Diseases ; Mortality ; Prospective Studies ; Republic of Korea ; Risk Factors ; Siblings ; Telephone ; Ultrasonography ; Urinalysis

PURPOSE: Asthma is a common disease that is expensive and burdensome for patients. Inhaled corticosteroids (ICS) are the most important drugs for asthma treatment and are often prescribed long-term. However, the use of ICS has been reported to increase pneumonia, though this remains controversial. We evaluated whether the use of ICS increases the risk of pneumonia in asthmatic patients using the Health Insurance Review and Assessment Service (HIRA) database in Korea. METHODS: The Asthma Management Adequacy Assessment was performed by the HIRA in Korea. Patients with claimed insurance benefits for asthma disease codes and who were prescribed asthma medications more than 2 times were enrolled. Patient demographics, asthma medications, healthcare use, and complications were analyzed. RESULTS: The total number of asthma patients was 831,613. Patients using ICS were older and had more comorbidities than those not using ICS; they also visited outpatient clinics and emergency departments, and were more often hospitalized. Pneumonia and other complications occurred more often in patients using ICS, and they used more respiratory medications, except for theophylline. Multiple logistic regression analysis showed that ICS prescription was associated with pneumonia (odds ratio, 1.38; 95% confidence interval, 1.36-1.41). Age, sex, medical care, use of secondary and tertiary hospitals, and hospitalization due to asthma in the previous year were also associated with pneumonia. CONCLUSIONS: ICS use was associated with increasing pneumonia in asthmatic patients in Korea. Therefore, it is critical to acknowledge that the use of ICS may increase the risk of pneumonia and should be meticulously monitored in asthmatics.
Adrenal Cortex Hormones ; Ambulatory Care Facilities ; Asthma ; Comorbidity ; Delivery of Health Care ; Demography ; Emergency Service, Hospital ; Hospitalization ; Humans ; Insurance Benefits ; Insurance, Health ; Korea ; Logistic Models ; Pneumonia ; Prescriptions ; Steroids ; Tertiary Care Centers ; Theophylline

BACKGROUND AND OBJECTIVES: This study aimed to investigate the right-left arm difference in detection of hypertension in the general Korean population. METHODS: This study analyzed data from the Cardiovascular and Metabolic Disease Etiology Research Center cohort. Study population was 2,103 people who were aged 30 to 64 years old, without history of major cardiovascular diseases, and did not use antihypertensive medication. Brachial blood pressures (BPs) were measured for both arms using an automated oscillometric device equipped with 2 cuffs for simultaneous double-arm measurements. Systolic and diastolic blood pressures (SBP and DBP) were measured 3 times, and the average value was used in the analysis. Overall hypertension was defined as elevated blood pressure (SBP/DBP ≥140/90 mmHg) at the arm with higher value, while right-arm or left-arm hypertension was defined as elevated BP at each arm. Sensitivity was calculated as the number of each-arm hypertension divided by the number of overall hypertension. RESULTS: Overall 8.6% of the population had hypertension at either arm, while 7.8% had right-arm hypertension, 7.2% had left-arm hypertension, and 6.4% had both arms hypertension. The sensitivity for the detection of hypertension was 90.6% when BP was measured only at right arm, and 83.4% when measured only at left arm. Corresponding sensitivity were 87.9% and 87.1% in men, and 95.4% and 76.9% in women. CONCLUSIONS Single-arm measurements, compared to double-arm measurements, may underestimate the prevalence of hypertension. However, if double-arm measurements are unavailable, right arm is preferred for measurement of BP, especially in women.

OBJECTIVE: Productivity loss was compared by 3-stage of disease activity and associations between higher disease activity and high productivity loss were identified. METHODS: Data were extracted from Rheumatoid Arthritis (RA) Patient-reported Outcomes Research, which enrolled 2,000 RA patients (>20-year) on disease-modifying-antirheumatic-drugs (DMARDs) (≥6-month) from December 2012 to June 2013. This included 1,457 RA patients with the disease activity score (DAS-28-ESR) in their medical charts. Productivity loss in time and indirect cost was estimated using The World Health Organization Health and Work Performance Questionnaire (HPQ). Baseline characteristics and productivity loss outcomes were compared according to DAS-28-ESR groups. RESULTS: 84.4% were females, 54.2% had low DAS-28-ESR ( < 3.2), and 38.2% and 7.6% had moderate (3.2∼5.1) and high DAS-28-ESR (>5.1). Patients with moderate to high DAS-28-ESR had higher lost productivity time (LPT) and monthly costs of LPT than those with low DAS-28-ESR (time in hours: 110.0±58.4 vs. 132.4±57.2 vs. 71.5±52.0, p < 0.0001; monthly costs of LPT in 1,000 Korean won: 1,097±607 vs. 1,302±554 vs. 741±531, p < 0.0001). Multiple regression analyses revealed significant associations with high LPT in high (adjusted odds ratio [OR]=3.87, 95% confidence interval [CI]: 2.18∼6.87) and moderate DAS-28-ESR (adjusted OR=1.88, 95% CI: 1.41∼2.52) compared to low DAS-28-ESR. In addition, positive associations with high monthly costs of LPT were observed in high (adjusted OR=3.45, 95% CI: 1.98∼5.99) and moderate DAS-28-ESR (adjusted OR=1.93, 95% CI: 1.43∼2.54) compared to low DAS-28-ESR. CONCLUSION: Timely therapeutic strategies should be taken into consideration given that the RA patients with moderate to high DAS-28-ESR showed strong associations with high productivity loss for effective management of RA.
Arthritis, Rheumatoid* ; Efficiency* ; Female ; Humans ; Odds Ratio ; Outcome Assessment (Health Care) ; Work Performance ; World Health Organization

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.
Animals ; Asthma ; Bronchoalveolar Lavage ; Common Cold ; Granulocytes ; Heat-Shock Proteins* ; HeLa Cells ; Hot Temperature* ; Humans ; In Vitro Techniques ; Lung ; Mice ; Molecular Chaperones ; Monocytes ; Respiratory System ; Rhinovirus* ; RNA Viruses

OBJECTIVES: The combined effects of obesity and appendicular skeletal muscle (ASM) on atherosclerosis, especially in middle-aged populations, remain poorly understood. This cross-sectional study investigated the effects of ASM on carotid intima-media thickness (IMT) according to body mass index (BMI) in middle-aged Korean adults. METHODS: Herein, 595 men and 1,274 women aged 30–64 years completed questionnaires and underwent health examinations as part of the Cardiovascular and Metabolic Disease Etiology Research Center cohort. ASM was measured via bioelectrical impedance analysis and adjusted for weight (ASM/Wt). IMT was assessed using B-mode ultrasonography; highest quartile of IMT was defined as gender-specific top quartile of the IMT values. Higher BMIs was defined as a BMI over 25.0 kg/m2. RESULTS: Compared to the highest ASM/Wt quartile, the lowest ASM/Wt quartile was significantly associated with highest quartile of IMT in men with lower BMIs (adjusted odds ratio [aOR], 2.78; 95% confidence interval [CI], 1.09 to 7.13), but not in those with higher BMIs (aOR, 0.59; 95% CI, 0.24 to 1.91). In women, there was no significant association of low skeletal muscle mass with highest quartile of IMT, regardless of BMI. CONCLUSION: Low appendicular skeletal muscle mass is associated with carotid arterial wall thickening in men with lower BMIs, but not in men with higher BMIs. Our findings suggest that the risk of atherosclerosis may be low in middle-aged Korean men with appropriate body weight and skeletal muscle mass maintenance.
Adult* ; Atherosclerosis ; Body Composition ; Body Mass Index* ; Body Weight ; Carotid Intima-Media Thickness* ; Cohort Studies ; Cross-Sectional Studies ; Electric Impedance ; Female ; Humans ; Male ; Metabolic Diseases ; Muscle, Skeletal* ; Muscles ; Obesity ; Odds Ratio ; Sarcopenia ; Ultrasonography