Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data.

BACKGROUND AND OBJECTIVES: The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. METHODS: We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. RESULTS: The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. CONCLUSIONS: Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Do dielectric bilayer metasurfaces behave as a stack of decoupled single-layer metasurfaces?

Flat optics or metasurfaces have opened new frontiers in wavefront shaping and its applications. Polarization optics is one prominent area which has greatly benefited from the shape-birefringence of metasurfaces. However, flat optics comprising a single layer of meta-atoms can only perform a subset of polarization transformations, constrained by a symmetric Jones matrix. This limitation can be tackled using metasurfaces composed of bilayer meta-atoms but exhausting all possible combinations of geometries to build a bilayer metasurface library is a very daunting task. Consequently, bilayer metasurfaces have been widely treated as a cascade (product) of two decoupled single-layer metasurfaces. Here, we test the validity of this assumption for dielectric metasurfaces by considering a metasurface made of titanium dioxide on fused silica substrate at a design wavelength of 532 nm. We explore regions in the design space where the coupling between the top and bottom layers can be neglected, i.e., producing a far-field response which approximates that of two decoupled single-layer metasurfaces. We complement this picture with the near-field analysis to explore the underlying physics in regions where both layers are strongly coupled. We also show the generality of our analysis by applying it to silicon metasurfaces at telecom wavelengths. Our unified approach allows the designer to efficiently build a multi-layer dielectric metasurface, either in transmission or reflection, by only running one full-wave simulation for a single-layer metasurface.

Prediction Model for Annual Variation in Total Pollen by Allergenic Trees in Korean Cities.

PURPOSE: Pollen forecasting systems can provide information for coping with respiratory allergies. They estimate daily pollen production, dispersal, deposition, and removal based on daily weather conditions to predict daily pollen concentrations and provide allergy warnings. As of 2023, the Korea Meteorological Administration (KMA) provides 2-day forecast of allergenic pollens. However, unlike these models, long-term analysis of annual observations of tree pollen reveal annual variations. Therefore, in this study, we aimed to develop annual prediction models for allergenic tree pollens based on long-term multi-site pollen and meteorological data. METHODS: Daily pollen concentrations were observed using Hirst-type volumetric spore traps at nine sites in Korea from 1998 to 2021, and daily weather data from the closest KMA stations were utilized. Models were developed to predict the seasonal pollen integral of seven tree species based on monthly mean temperature, wind speed, and total precipitation using three variable selection methods: 1) the t-test based key variable screening followed by linear regression with stepwise procedure (TM), 2) direct linear regression with stepwise procedure from the full variable model (FM), and 3) LASSO regression from the full variable model (LM). RESULTS: Data obtained during 1998-2017 and 2018=2021 were utilized for model development and validation, respectively. The root mean squared error, mean absolute error, mean error, and coefficient of determination (R²) revealed that the TM models were best suited for actual forecasting, even though R² in the TM model was lower than those of the FM and LM models. CONCLUSIONS: The annual variation model in this study can be integrated with the daily pollen forecast model by controlling the annual pollen potential, and the accuracy of the daily forecast can be improved accordingly.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Development of a Simulation Model for Digital Twin of an Oscillating Water Column Wave Power Generator Structure with Ocean Environmental Effect.

This research article focuses on developing a baseline digital twin model for a wave power generator structure located in Yongsu-ri, Jeju-do, South Korea. First, this study performs a cause analysis on the discrepancy of the dynamic properties from the real structure and an existing simulation model and finds the necessity of modeling the non-structural masses and the environmental factors. The large amounts of the ballast are modeled in the finite element model to enhance the accuracy of the digital twin. Considering the influence of environmental factors such as tide level and wave direction, the added mass effect of structural members, one of the hydrodynamic effects, depending on the change of the ocean environments is calculated based on the rule of Det Norske Veritas and applied. The results indicate that non-structural mass components significantly impact the dynamic characteristics of the structure. Additionally, environmental factors have a greater effect on the dynamic behavior of the box-type structure compared to lightweight offshore structures.

Annual Change in Fungal Concentrations and Allergic Sensitization Rates to Alternaria and Cladosporium in Korea During the Period 1998-2022.

PURPOSE: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years. METHODS: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration. RESULTS: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children. CONCLUSIONS: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.

C-reactive protein accelerates DRP1-mediated mitochondrial fission by modulating ERK1/2-YAP signaling in cardiomyocytes.

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRPinduced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage. [BMB Reports 2023; 56(12): 663-668].

Association between frailty and physical performance in older patients with heart failure.

BACKGROUND: Frailty is an issue in patients with heart failure (HF). A Korean version of the frailty scale (K-FRAIL) has been developed. HYPOTHESIS: We aimed to analyze the relationship between the K-FRAIL scale and physical performance in patients with HF. METHODS: This study included 142 patients with HF aged ≥65 years from a single center. Muscular fitness was assessed using the handgrip test and knee extensor strength measurement. Aerobic capacity was assessed using the cardiopulmonary exercise test and 6-min walk test (6MWT). Frailty was assessed using the K-FRAIL questionnaire. RESULTS: Peak VO2 and 6MWT scores significantly decreased as frailty worsened, but handgrip and knee extensor strength did not. In the multivariate analysis, peak VO2 (ß = -.31; p = .002) and 6MWT score (ß = -.38; p < .001) showed significant inverse associations with the K-FRAIL score. Based on the receiver operating characteristic curve analysis, the cut-off values of peak VO2 (hazard ratio, 5.08; p = .023) and 6MWT (hazard ratio, 3.99; p = .020) were independent predictors of frailty. CONCLUSION: In older patients with HF, physical performance correlates with the degree of frailty. The K-FRAIL scale is correlated with the peak VO2 and 6MWT.

The Association Between On-treatment Ambulatory Central Blood Pressure and Left Ventricular Reverse Remodeling in Heart Failure With Reduced Ejection Fraction.

Background and Objectives: Compared to office blood pressure (OBP), central blood pressure (CBP) and ambulatory blood pressure (BP) are known to be better markers for predicting cardiovascular events. We evaluated the association between left ventricular reverse remodeling (LVRR) and ambulatory CBP in heart failure with reduced ejection fraction (HFrEF). Methods: This study retrospectively analyzed 93 patients who performed ambulatory CBP and brachial BP (BBP) monitoring from 2018 to 2020 within 1 year after diagnosis of HFrEF at a single tertiary center. We analyzed the association between on-treatment ambulatory BPs and LVRR on follow-up echocardiography. Results: The mean age of participants was 59 years; 65.6% were men; mean LVEF was 29%. Ambulatory BP and follow-up echocardiography were done at 143 days (interquartile range [IQR], 64-267) and 454 days (IQR, 281-600) after diagnosis of HF, respectively. Baseline OBP was not different between 2 groups, but ambulatory systolic CBP was significantly higher in the LVRR group than the non-LVRR group (p=0.005). Systolic OBP (odds ratio [OR], 1.029; confidence interval [CI], 1.004-1.055; p=0.026), 24-hour ambulatory systolic CBP (OR, 1.048; CI, 1.015-1.082; p=0.004), and 24-hour ambulatory systolic BBP (OR, 1.049; CI,1.017-1.082; p=0.003) were associated with LVRR. Compared to ambulatory systolic CBP of 110-119 mmHg, 90-99 mmHg showed lower OR for LVRR. Conclusions: Low on-treatment ambulatory systolic CBP was closely related to a lower likelihood of LVRR in HFrEF than the normal range. Ambulatory CBP measured during treatment of patients with HFrEF appears to be useful in predicting outcomes.

Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Hypertension and Cardiovascular Risk Factors.

INTRODUCTION: Patients with hypertension and additional cardiovascular risk factors pose a challenge by requiring more intensive blood pressure (BP) control. Single-pill combination (SPC) therapy can benefit these patients by improving medication adherence. METHODS: This prospective, multicenter observational study assessed the real-world safety and effectiveness of an SPC containing olmesartan, amlodipine, and hydrochlorothiazide (O/A/H) in South Korean patients with hypertension and cardiovascular risk factors. BP control rates, defined as the percentage of patients achieving systolic BP (SBP) < 130 mmHg and diastolic BP (DBP) < 80 mmHg for intensive BP control, and < 140 mmHg and < 90 mmHg, respectively, for standard BP control, were investigated across various cardiovascular risk groups, along with changes in SBP and DBP from baseline to week 24. RESULTS: The most prevalent cardiovascular risk factor was age (≥ 45 years in men, ≥ 55 years in women, 86.1%), followed by cardiovascular diseases (64.4%), dyslipidemia (53.7%), body mass index ≥ 25 kg/m2 (53.5%), and diabetes mellitus (DM) (46.3%). Switching to O/A/H showed significant BP reduction, with a mean change of - 17.8 mmHg/- 9.3 mmHg in SBP/DBP within 4 weeks. The intensive BP control rate was 41.4% (95% confidence interval [CI] 39.5, 43.4), and the standard BP control rate was 73.3% (95% CI 71.5, 75.1), with better control rates in the risk age group (43.1% and 74.1%, respectively) and cardiovascular disease group (42.0% and 73.8%, respectively). The DM group had relatively lower control rates (37.5% for intensive control and 69.4% for standard control). Common adverse drug reactions included dizziness (2.91%), hypotension (1.51%), and headaches (0.70%). CONCLUSION: The SPC therapy of O/A/H caused a rapid and sustained reduction in SBP/DBP in patients' hypertension and additional cardiovascular risk factors. The therapy was safe and well tolerated. STUDY REGISTRATION NUMBER: KCT0003401 ( https://cris.nih.go.kr/cris/search/detailSearch.do/20795 ).

Ultrastrong Coupling Enhancement with Squeezed Mode Volume in Terahertz Nanoslots.

Metallic nanogaps have emerged as a versatile platform for realizing ultrastrong coupling in terahertz frequencies. Increasing the coupling strength generally involved reducing the gap width to minimize the mode volume, which presents challenges in fabrication and efficient material coupling. Here, we propose employing terahertz nanoslots, which can efficiently squeeze the mode volume in an extra dimension alongside the gap width. Our experiments using 500 nm wide nanoslots integrated with an organic-inorganic hybrid perovskite demonstrate ultrastrong phonon-photon coupling with a record-high Rabi splitting of 48% of the original resonance (Ω = 0.48ω0), despite having a gap width 5 times larger than previously reported structures with Ω = 0.45ω0. Mechanisms underlying this effective light--matter coupling are investigated with simulations using coupled mode theory. Moreover, bulk polariton analyses reveal that our results account for 68% of the theoretical maximum Rabi splitting, with the potential to reach 82% through further optimization of the nanoslots.

Clinical Implications of Device-Detected Atrial Fibrillation in Cardiac Resynchronization Therapy.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. METHODS: We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. RESULTS: A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The device-detected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. CONCLUSIONS: For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.

COVID-19 in the Asia Pacific: Impact on climate change, allergic diseases and One Health.

Climate change and environmental factors such as air pollution and loss of biodiversity are known to have a major impact not only on allergic diseases but also on many noncommunicable diseases. Coronavirus disease 2019 (COVID-19) resulted in many environmental changes during the different phases of the pandemic. The use of face masks, enhanced hand hygiene with hand rubs and sanitizers, use of personal protective equipment (gowns and gloves), and safe-distancing measures, reduced the overall incidence of respiratory infections and other communicable diseases. Lockdowns and border closures resulted in a significant reduction in vehicular traffic and hence environmental air pollution. Paradoxically, the use of personal protective equipment and disposables contributed to an increase in environmental waste disposal and new problems such as occupational dermatoses, especially among healthcare workers. Environmental changes and climate change over time may impact the exposome, genome, and microbiome, with the potential for short- and long-term effects on the incidence and prevalence of the allergic disease. The constant use and access to mobile digital devices and technology disrupt work-life harmony and mental well-being. The complex interactions between the environment, genetics, immune, and neuroendocrine systems may have short- and long-term impact on the risk and development of allergic and immunologic diseases in the future.

Seasonal differences in the effects of local concentrations of atmospheric substances and meteorological elements on asthma exacerbation of children in metropolitan area, Korea: A 13-year retrospective single-center study.

Purpose: Air pollutants contribute to asthma exacerbation, and the types of air pollutants involved in acute asthma exacerbation may differ depending on climate and environmental conditions. This study aimed to identify factors affecting asthma exacerbation in each of the four seasons so that to prevent acute asthma exacerbation and to establish effective treatment strategies for each season. Methods: Pediatric patients aged 0-18 years old hospitalized or admitted to the emergency room for asthma exacerbation at Hanyang University Guri Hospital between January 1, 2007, and December 31, 2019 were recruited. The number of asthma exacerbations comprised the total number of patients admitted to the emergency room or hospitalized for asthma and treated with systemic steroids. The association between the number of asthma exacerbations/week and average concentrations of atmospheric substances and meteorological elements in that week were analyzed. Multiple linear regression analyses were performed to examine the association between various atmospheric variables and the number of asthma exacerbations. Results: The number of asthma exacerbations was found to be associated with the concentration of particulate matter with an aerodynamic diameter of ≤10 µm in that week in autumn. No atmospheric variables exhibited an association in other seasons. Conclusions: Air pollutants and meteorological factors affecting asthma exacerbation vary by season. Moreover, their effects may change via their interaction with each other. The results of this study suggest that it will be helpful to establish differentiated measures for each season to prevent asthma exacerbation.