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Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b (Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging.
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We undertook a comprehensive investigation of the electronic structure of FeSe, known as a Hund metal, and found that it is not uniquely defined. Through accounting for all two-particle irreducible diagrams constructed from electron Green's function G and screened Coulomb interaction W in a self-consistent manner, a Mott-insulator phase of 2D-FeSe is unveiled. The metal-insulator transition is driven by the strong on-site Coulomb interaction in its paramagnetic phase, accompanied by the weakening of both local and nonlocal screening effects on the Fe-3d orbitals. Our results suggest that Mott physics may play a pivotal role in shaping the electronic, optical, and superconducting properties of monolayer or nanostructured FeSe.
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Murine models of obesity or reduced adiposity are a valuable resource for understanding the role of adipocyte dysfunction in metabolic disorders. Adipose tissue stromal vascular cells or primary adipocytes derived from murine adipose tissue and grown in culture are essential tools for studying the mechanisms underlying adipocyte development and function. Herein, we describe methods for the isolation, expansion, and long-term storage of murine adipose-derived stromal/stem cells, along with protocols for inducing adipogenesis to white or beige adipocytes in this cell population and osteogenic differentiation. Isolation of the adipose stromal vascular fraction cells for flow cytometric analysis is also described.
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Adipogénesis , Adiposidad , Ratones , Humanos , Animales , Citometría de Flujo/métodos , Osteogénesis , Adipocitos , Tejido Adiposo , Diferenciación Celular , Obesidad/metabolismo , Células MadreRESUMEN
Objectives@#Excess mortality associated with long-term exposure to fine particulate matter (PM2.5) has been documented. However, research on the disease burden following short-term exposure is scarce. We investigated the cause-specific mortality burden of short-term exposure to PM2.5 by considering the potential non-linear concentration–response relationship in Korea. @*Methods@#Daily cause-specific mortality rates and PM2.5 exposure levels from 2010 to 2019 were collected for 8 Korean cities and 9 provinces. A generalized additive mixed model was employed to estimate the non-linear relationship between PM2.5 exposure and cause-specific mortality levels. We assumed no detrimental health effects of PM2.5 concentrations below 15 μg/m3. Overall deaths attributable to short-term PM2.5 exposure were estimated by summing the daily numbers of excess deaths associated with ambient PM2.5 exposure. @*Results@#Of the 2 749 704 recorded deaths, 2 453 686 (89.2%) were non-accidental, 591 267 (21.5%) were cardiovascular, and 141 066 (5.1%) were respiratory in nature. A non-linear relationship was observed between all-cause mortality and exposure to PM2.5 at lag0, whereas linear associations were evident for cause-specific mortalities. Overall, 10 814 all-cause, 7855 non-accidental, 1642 cardiovascular, and 708 respiratory deaths were attributed to short-term exposure to PM2.5. The estimated number of all-cause excess deaths due to short-term PM2.5 exposure in 2019 was 1039 (95% confidence interval, 604 to 1472). @*Conclusions@#Our findings indicate an association between short-term PM2.5 exposure and various mortality rates (all-cause, non-accidental, cardiovascular, and respiratory) in Korea over the period from 2010 to 2019. Consequently, action plans should be developed to reduce deaths attributable to short-term exposure to PM2.5.
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Objectives@#Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. @*Methods@#We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the correspondingsampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic ofKorea were estimated by applying the algorithms and weighted PPV and NPV to the 2018National Health Insurance Service claims data. @*Results@#In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. @*Conclusion@#This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.
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Objective@#This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. @*Methods@#Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). @*Results@#The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. @*Conclusion@#The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.
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Probiotics, including Lacticaseibacillus rhamnosus (L. rhamnosus), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of L. rhamnosus LM1019 (LM1019) in enhancing immune function. In RAW 264.7 cells, LM1019 demonstrated dose-dependent immune stimulation by increasing nitric oxide production, gene expression of proinflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were mediated through the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) translocation without inducing cytotoxicity. Furthermore, orally administered LM1019 was evaluated in immunosuppressed mice induced by cyclophosphamide (CTX). High-dose administration of LM1019 significantly increased the subpopulations of lymphocytes, specifically helper T cells (CD4+), as well as two subtypes of natural killer (NK) cells, namely, IFN-γ+ and granzyme B+ NK cells. Additionally, LM1019 at a high dose led to elevated levels of proinflammatory cytokines, including IFN-γ and IL-12, compared to CTX-treated mice. These findings highlight the potential of LM1019 in enhancing the immune system. The study contributes to the growing body of research on the beneficial effects of probiotics on immune function.
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Microplastics (MPs) are now a global issue due to increased plastic production and use. Recently, various studies have been performed in response to the human health risk assessment. However, these studies have focused on spherical MPs, which have smooth edges and a spherical shape and account for less than 1% of MPs in nature. Unfortunately, studies on fragment-type MPs are very limited and remain in the initial stages. In this study, we studied the effect that 16.4 µm fragment type polypropylene (PP) MPs, which have an irregular shape and sharp edges and form naturally in the environment, had on breast cancer. The detrimental effects of PPMPs on breast cancer metastasis were examined. Here, 1.6 mg/ml of PPMP, which does not induce cytotoxicity in MDA-MB-231, was used, and at this concentration, PPMP did not induce morphological changes or cellular migrating in the MDA-MB-231 and MCF-7 cells. However, PPMP incubation for 24 hours in the MDA-MB-231 cells significantly altered the level of cell cycle-related transcripts in an RNA-seq analysis. When confirmed by qRT-PCR, the gene expression of TMBIM6, AP2M1, and PTP4A2 was increased, while the transcript level of FTH1 was decreased. Further, secretion of the pro-inflammatory cytokine IL-6 from cancer cells was elevated with the incubation of PPMP for 12 hours. These results suggest that PPMP enhances metastasis-related gene expression and cytokines in breast cancer cells, exacerbating breast cancer metastasis.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Polipropilenos , Microplásticos , Plásticos , Citocinas , Proteínas de la Membrana , Proteínas Reguladoras de la Apoptosis , Proteínas Tirosina FosfatasasRESUMEN
An integrated textile electronic system is reported here, enabling a truly free form factor system via textile manufacturing integration of fiber-based electronic components. Intelligent and smart systems require freedom of form factor, unrestricted design, and unlimited scale. Initial attempts to develop conductive fibers and textile electronics failed to achieve reliable integration and performance required for industrial-scale manufacturing of technical textiles by standard weaving technologies. Here, we present a textile electronic system with functional one-dimensional devices, including fiber photodetectors (as an input device), fiber supercapacitors (as an energy storage device), fiber field-effect transistors (as an electronic driving device), and fiber quantum dot light-emitting diodes (as an output device). As a proof of concept applicable to smart homes, a textile electronic system composed of multiple functional fiber components is demonstrated, enabling luminance modulation and letter indication depending on sunlight intensity.
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Endophytes can facilitate the improvement of plant growth and health in agriculturally important crops, yet their genomes and secondary metabolites remain largely unexplored. We previously isolated Saccharibacillus brassicae strain ATSA2T from surface-sterilized seeds of kimchi cabbage and represented a novel species of the genus Saccharibacillus. In this study, we evaluated the plant growth-promoting (PGP) effect of strain ATSA2T in kimchi cabbage, bok choy, and pepper plants grown in soils. We found a significant effect on the shoot and root biomass, and chlorophyll contents following strain ATSA2T treatment. Strain ATSA2T displayed PGP traits such as indole acetic acid (IAA, 62.9 µg/mL) and siderophore production, and phosphate solubilization activity. Furthermore, genome analysis of this strain suggested the presence of gene clusters involved in iron acquisition (fhuABD, afuABC, fbpABC, and fepCDG) and phosphate solubilization (pstABCHS, phoABHLU, and phnCDEP) and other phytohormone biosynthesis genes, including indole-3-acetic acid (trpABCDEFG), in the genome. Interestingly, the secondary metabolites cerecidin, carotenoid, siderophore (staphylobactin), and bacillaene underlying plant growth promotion were found in the whole genome via antiSMASH analysis. Overall, physiological testing and genome analysis data provide comprehensive insights into plant growth-promoting mechanisms, suggesting the relevance of strain ATSA2T in agricultural biotechnology.
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BACKGROUND: The transcription factor orthodenticle homeobox 2 (OTX2) has critical functions in brain and eye development, and its mutations in humans are related to retinal diseases, such as ocular coloboma and microphthalmia. However, the regulatory mechanisms of OTX2 are poorly identified. OBJECTIVE: The identification of JNK1 as an OTX2 regulatory protein through the protein interaction and phosphorylation. METHODS: To identify the binding partner of OTX2, we performed co-immunoprecipitation and detected with a pooled antibody that targeted effective kinases. The protein interaction between JNK1 and OTX2 was identified with the co-immunoprecipitation and immunocytochemistry. In vivo and in vitro kinase assay of JNK1 was performed to detect the phosphorylation of OTX2 by JNK1. RESULTS: JNK1 directly interacted with OTX2 through the transactivation domain at the c-terminal region. The protein-protein interaction and co-localization between JNK1 and OTX2 were further validated in the developing P0 mouse retina. In addition, we confirmed that the inactivation of JNK1 K55N mutant significantly reduced the JNK1-mediated phosphorylation of OTX2 by performing an immune complex protein kinase assay. CONCLUSION: c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor through the protein-protein interaction.
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Proteína Quinasa 8 Activada por Mitógenos , Factores de Transcripción Otx , Retina , Animales , Humanos , Ratones , Regulación de la Expresión Génica , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Factores de Transcripción Otx/genética , Factores de Transcripción Otx/metabolismo , Fosforilación , Unión Proteica , Factores de Transcripción/genética , Retina/metabolismoRESUMEN
Objective@#Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse (CDW). @*Methods@#We conducted a cohort search in the CDW application and got 260 patients’ medical records diagnosed with schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders who were taking one of risperidone, blonanserin, amisulpride, and olanzapine. After that, we reviewed the medical data and used the ANCOVA analysis and the post hoc test to compare serum prolactin levels among four antipsychotic drug groups. @*Results@#Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.6 ± 54.6 ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between sex in the subjects who took amisulpride. @*Conclusion@#This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.
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Complete genome sequence analysis of Bifidobacterium longum subsp. longum BCBL-583 isolated from a Korean female fecal sample showed no virulence factor or antibiotic resistance gene, suggesting human safety. In addition, this strain has oxygen and heat tolerance genes for food processing, and cholesterol reduction and mucin adhesion-related genes were also found. For in vivo evaluations, a high fat diet (HFD) mouse model was used, showing that BCBL-583 administration to the model (HFD-583) reduced the total cholesterol and LDL-cholesterol in the blood and decreased pro-inflammatory cytokines but increased anti-inflammatory cytokines, substantiating its cholesterol reduction and anti-inflammation activities. Subsequent microbiome analysis of the fecal samples from the HFD mouse model revealed that BCBL-583 administration changed the composition of gut microbiota. After 9 weeks feeding of bifidobacteria, Firmicutes, Actinobacteria, and Bacteroidetes increased, but Proteobacteria maintained in the HFD mouse models. Further comparative species-level compositional analysis revealed the inhibitions of cholesterol reduction-related Eubacterium coprostanoligenes and obesity-related Lactococcus by the supplementation of B. longum BCBL-583, suggesting its possible cholesterol reduction and anti-obesity activities. The correlation analysis of HFD-583 between the gut microbiota compositional change and cholesterol/immune response showed that Verrucomicrobia, Firmicutes, Actinobacteria, and Bacteroidetes may play an important role in cholesterol reduction and anti-inflammation. However, correlation analysis of Proteobacteria showed the reverse correlation in HFD-583. Interestingly, the correlation analysis of B. longum ATCC 15707 administration to HFD model showed similar patterns of cholesterol but different in immune response patterns. Therefore, this correlation analysis suggests that the microbial composition and inflammatory cytokine/total-cholesterol may be closely related in the administration of BCBL-583 in the HFD mice group. Consequently, BCBL-583 could be a good probiotic strain for gut health promotion through gut microbiota modulation.
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To investigate the CGE on hair growth and to explore the mechanism that is involved in the acceleration of anagen induction, we investigated the effects of CGE studied on cell proliferation and molecular mechanism in human hair dermal papilla cells (hDPCs) and keratinocytes (HaCaT cells). Additionally, hair growth evaluation was carried out following topical treatment of the dorsal skin of telogen C57BL/6 mice with CGE for 14 days. As result, CGE increased cell viability and ALP activity in hDPCs. Moreover, CGE increased the expression of catenin beta 1 (CTNNB1), ALP, sex-determining region Y-box 2 (SOX2), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor A (VEGFA) genes in hDPCs. CGE increased the expression of proteins such as ALP, ß-catenin, and phosphorylation of glycogen synthase kinase 3ß (pGSK3ß), and protein kinase B (pAKT) in hDPCs. Furthermore, CGE induced the proliferation of HaCaT cells and up-regulated AKT-ERK-GSKß-ß-catenin signaling in HaCaT cells. Additionally, the anagen induction effects of CGE were confirmed on the telogen-anagen transition mice model. these findings demonstrated that CGE promoted the entering the growth phase of hair follicle via activation of ß-catenin signaling pathways in vivo. Thus, this study suggests that CGE might be a potential therapeutic reagent for hair growth.
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Factor A de Crecimiento Endotelial Vascular , beta Catenina , Animales , Proliferación Celular , Células Cultivadas , Cabello , Folículo Piloso/metabolismo , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Smart textiles consist of discrete devices fabricated from-or incorporated onto-fibres. Despite the tremendous progress in smart textiles for lighting/display applications, a large scale approach for a smart display system with integrated multifunctional devices in traditional textile platforms has yet to be demonstrated. Here we report the realisation of a fully operational 46-inch smart textile lighting/display system consisting of RGB fibrous LEDs coupled with multifunctional fibre devices that are capable of wireless power transmission, touch sensing, photodetection, environmental/biosignal monitoring, and energy storage. The smart textile display system exhibits full freedom of form factors, including flexibility, bendability, and rollability as a vivid RGB lighting/grey-level-controlled full colour display apparatus with embedded fibre devices that are configured to provide external stimuli detection. Our systematic design and integration strategies are transformational and provide the foundation for realising highly functional smart lighting/display textiles over large area for revolutionary applications on smart homes and internet of things (IoT).
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Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.
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Silica-supported lanthanum (III) chloride (SiO2-LaCl3·7H2O) was prepared and characterized by infrared spectroscopy, X-ray diffraction analysis, scanning electron microscope, energy-dispersive X-ray spectroscopy, thermogravimetric analysis and differential thermal analysis techniques. The catalytic activity of this silica-supported lanthanum (III) chloride was investigated in a one-pot three-component Kabachnik-Fields reaction. A library of new α-aminophosphonates was prepared employing various benzothiazole and thiadiazole amines, different substituted aldehydes and diethylphosphite under solvent-free conditions using conventional/microwave methods with good to excellent yields (85-97%). The advantages of this catalyst are that it is environmentally benign, economically inexpensive, and easy to prepare, gives high yields and high purity is less time-consuming, offers easy purification is reusable and enables products to be obtained by simple recrystallization without column chromatography.
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Antiinfecciosos , Organofosfonatos , Tiadiazoles , Aldehídos , Aminas/química , Benzotiazoles , Cloruros , Lantano , Microondas , Organofosfonatos/química , Dióxido de Silicio/químicaRESUMEN
OBJECTIVES@#We investigated the awareness, experience, approval, intention to use, and the desired type of telemedicine among Korean general public. @*METHODS@#From November to December 2020, we conducted an online self-reported survey on awareness, experience, approval, and intent to use telemedicine services among Korean residents aged 20 years or older. A total of 2,097 participants completed the survey. @*RESULTS@#Of the 2,097 participants, 1,558 (74.3%) were aware of, 1,198 (57.1%) approved of, and 1,474 (70.3%) had the intention to use telemedicine. Participants from regions other than the Seoul metropolitan area and Daegu–Gyeongbuk Province (adjusted odds ratio [aOR], 1.29; 95% confidence interval [CI], 1.02 to 1.63), households with a monthly household income of US$6,000 or more (aOR, 1.44; 95% CI, 1.01 to 2.08), participants who had a college/university or associate’s degree (aOR, 1.35. 95% CI, 1.04 to 1.75) or a master’s degree or above (aOR, 1.73; 95% CI, 1.20 to 2.50), and housewives (aOR, 1.30; 95% CI, 1.03 to 1.64) had higher odds of approval. Elderly participants, those with a chronic disease (aOR, 1.26; 95% CI, 1.04 to 1.54), those who had experienced delays of healthcare services (aOR, 1.94; 95% CI, 1.27 to 2.96), and those who had experience with telemedicine (aOR, 4.28; 95% CI, 1.69 to 10.82) were more likely to intend to use telemedicine services. Regarding types of telemedicine, teleconsultation between doctors showed the highest approval rate (73.1%). @*CONCLUSIONS@#In the context of the coronavirus disease 2019 pandemic, more than 70% of participants had already used or intended to use telemedicine at some point. Groups with a substantial need for telemedicine were more in favor of telemedicine.
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OBJECTIVES@#The aim of this study was to estimate the age-specific effects of 8-hour maximum ozone levels on pneumonia in children and adolescents. @*METHODS@#We performed quasi-Poisson regression analyses for individuals of 0-4 years, 5-9 years, 10-14 years, and 15-19 years of age using nationwide time-series data from the Korea (2011-2015). We constructed distributed lag linear models employing a generalized difference-in-differences method and controlling for other air pollutants. @*RESULTS@#A 10.0-parts per billion increase in 8-hour maximum ozone levels was associated with a higher risk of hospital admissions due to pneumonia at 0-4 (relative risk [RR], 1.02; 95% confidence interval [CI], 1.01 to 1.03) and 5-9 years of age (RR, 1.06; 95% CI, 1.04 to 1.08), but not at 10-14 (RR, 1.01; 95% CI, 0.98 to 1.04) or 15-19 years of age (RR, 1.01; 95% CI, 0.97 to 1.06). The association between ozone and hospital admissions due to pneumonia was stronger in cool seasons (from November to April) than in warm seasons (from May to October), but was similar between boys and girls. @*CONCLUSIONS@#Short-term exposure to ozone was associated with a higher risk of pneumonia at 0-4 years and 5-9 years of age, but not at 10-14 years or 15-19 years of age. Our findings can help identify vulnerable periods, determine the target populations for public health interventions, and establish air pollution standards.