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Eun Jung Bae,1,* Soo-Hyun Nam2,* 1College of Nursing, Seoul National University, Seoul, Republic of Korea; 2Department of Nursing, Andong National University, Andong, Republic of Korea*These authors contributed equally to this workCorrespondence: Soo-Hyun Nam, Department of Nursing, Andong National University, 1375 Gyeongdong-ro, Andong, Gyeongbuk, 36729, Republic of Korea, Tel +82-54-820-6772, Fax +82-54-820-9415, Email snam@anu.ac.krPurpose: This study aimed to investigate the serial mediating effects of the time mothers spend with their adolescent children and the adolescents’ self-esteem on the relationship between mothers’ and adolescents’ problematic smartphone use.Patients and Methods: This study was a secondary analysis of data extracted from the Korean Children and Youth Panel Survey (KCYPS) in 2018, which comprised data on first-year middle school students. Mediation analysis was conducted using Model 6 of the Hayes’ PROCESS macro for SPSS.Results: The mediating effect of the time mothers spent with adolescents on the relationship between mothers’ and adolescents’ problematic smartphone use was significant, but the mediating effect of adolescents’ self-esteem was not significant. Mothers’ problematic smartphone use was found to significantly affect adolescents’ problematic smartphone use by sequentially mediating the time mothers spent with adolescent children and adolescents’ self-esteem.Conclusion: It was concluded that, to lower adolescents’ problematic smartphone use due to mothers’ problematic smartphone use, appropriate interventions should be formulated to help adolescents develop higher self-esteem through sufficient mother–child interaction time.Keywords: problematic smartphone use, mother–child relationship, adolescents self-esteem, mediation analysis

Wenting Xu, Eun Ju Bae, Mi-Kyung Lee Department of Pharmaceutical Sciences, Woosuk University, Jeonbuk, South Korea Purpose: The aim of this study was to show enhanced anticancer activity of paclitaxel (Ptx) incorporated into solid lipid nanoparticles (SLNs) and reveal reversal of multidrug resistance (MDR) by SLNs mediated by increased uptake through different entry mechanisms from that in drug-sensitive cells.Methods: Anticancer activity of Ptx incorporated in SLNs (Ptx-SLNs) was measured in the drug-sensitive human breast cancer cell line MCF7 and its MDR variant MCF7/ADR. Cellular uptake of cargo molecules in SLNs was compared using Ptx-SLNs and rhodamine 123-loaded SLNs (Rho-SLNs) in both cell lines. In addition, endocytic uptake was evaluated using genistein (Gen) and chlorpromazine (Cpz) as inhibitors of clathrin- and caveola-mediated endocytosis, respectively.Results: Ptx-SLNs showed remarkably enhanced anticancer activity in MCF7/ADR compared to Ptx delivered in dimethyl sulfoxide (DMSO) and Cremophor EL-based vehicles. SLNs significantly increased intracellular uptake of Ptx and Rho in MCF7/ADR. Western blotting demonstrated that clathrin was expressed in both cell lines, while caveolin 1 was expressed only in MCF7/ADR. In MCF7/ADR, uptake of Ptx-SLNs and Rho-SLNs was reduced by Gen, while there was no change by Cpz, suggesting the involvement of caveola-mediated endocytosis. Size reduction of Rho-SLNs through high-pressure homogenization (Rho-SLNs) appeared to cause a shift of the endocytosis mechanism from a clathrin-independent pathway to a clathrin-dependent one. In contrast to MCF7/ADR, the uptake of SLNs into MCF7 was not changed by Gen or Cpz, suggesting involvement of clathrin- and caveola-independent mechanism for the entry of SLNs.Conclusion: MDR was reversed by incorporating drug into SLNs, and the reversal was mediated by increased uptake of SLNs evading efflux pumps in MDR cells. The enhanced uptake could also be due to the use of different endocytosis pathways by SLNs in MDR cells from drug-sensitive cancer cells. Keywords: SLNs, MDR, paclitaxel, Pgp, breast cancer, endocytosis

A 34 months-old male patient with double inlet right ventricle with nonconfluent pulmonary arteries who underwent successful extracardiac fenestarated Fontan procedure using pre-designed T-shaped PTFE vascular graft after multi-step rehabilitation of the diminutive hilar pulmonary arteries. At first we performed 6 mm confluent pulmonary artery vascular graft implantation with 4 mm BT shunt at patient's 4 weeks old. At 9 months of patient, we upsized the confluent pulmonary arterial graft to 8 mm with bidirectional cavopulmonary connection, and, at 34 months, we performed extracardiac conduit Fontan procedure with pre-designed T-shape conduit including the confluent pulmonary arterial portion at last. Patient shows excellent functional status and development. [ABSTRACT FROM AUTHOR]

Traditional dental prosthetics require a significant amount of work, labor, and time. To simplify the process, a method to convert teeth scan images, scanned using an intraoral scanner, into 3D images for design was developed. Furthermore, several studies have used deep learning to automate dental prosthetic processes. Tooth images are required to train deep learning models, but they are difficult to use in research because they contain personal patient information. Therefore, we propose a method for generating virtual tooth images using image-to-image translation (pix2pix) and contextual reconstruction fill (CR-Fill). Various virtual images can be generated using pix2pix, and the images are used as training images for CR-Fill to compare the real image with the virtual image to ensure that the teeth are well-shaped and meaningful. The experimental results demonstrate that the images generated by the proposed method are similar to actual images. In addition, only using virtual images as training data did not perform well; however, using both real and virtual images as training data yielded nearly identical results to using only real images as training data., (© 2024. The Author(s).)

Objective: Intra-atrial reentrant tachycardia is an important late-onset complication in patients undergoing the Fontan procedure. However, the protective effects of prophylactic cryoablation against late-onset intra-atrial reentrant tachycardia are unclear. This study investigated the late development of intra-atrial reentrant tachycardia in patients undergoing the lateral tunnel Fontan procedure and the role of prophylactic cryoablation., Methods: This was a single-center retrospective cohort study of patients who underwent the lateral tunnel Fontan procedure between 1988 and 2003. Univariate and multivariable competing risks regression models were used to determine the associations of prophylactic cryoablation and covariates with the outcomes of interest: late-onset intra-atrial reentrant tachycardia, all-cause mortality, and cardiovascular mortality., Results: In total, 130 patients who underwent the lateral tunnel Fontan procedure, 30 of whom had undergone prophylactic cryoablation, were included in this study and followed up for a median of 23.6 years (interquartile range, 17.7-26.5). Intra-atrial reentrant tachycardia was identified in 14 patients (10.8%), none of whom underwent prophylactic cryoablation. The median Fontan-to-intra-atrial reentrant tachycardia time was 17.2 years (interquartile range, 11.1-23.1). Prophylactic cryoablation was protective against late-onset intra-atrial reentrant tachycardia (P < .0001) and cardiovascular mortality (P < .0001) in the type 3 test., Conclusions: None of the patients who underwent prophylactic cryoablation developed late-onset intra-atrial reentrant tachycardia during a median follow-up time of 22.9 years. Our study demonstrated that prophylactic cryoablation was effective in preventing late-onset intra-atrial reentrant tachycardia and cardiovascular mortality in patients undergoing the lateral tunnel Fontan., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Among inorganic thermoelectric materials, flexible thermoelectric materials have attracted considerable attention. In this study, highly flexible and plastically bendable silver selenide films with excellent thermoelectric performance at room temperature are presented. The flexibility of the freestanding silver selenide films was significantly improved through a simple annealing treatment. The highly flexible silver selenide films with a thickness of 26.0 μm displayed outstanding n-type thermoelectric performance, achieving an in-plane zT value of 0.38 at room temperature. Because silver selenide films are plastically bendable with a bending radius of less than 1 mm, they can be shaped into various forms. To achieve stretchability and skin-conformality in the thermoelectric generator, S-shaped silver selenide strips were used as an n-type thermoelectric element. Effective harvesting of electricity from heat of the human body was successfully demonstrated.

Neuropathological features of Alzheimer's disease include amyloid plaques, neurofibrillary tangles and Lewy bodies, with the former preceding the latter two. However, it is not fully understood how these compound proteinopathies are interconnected. Here, we show that transplantation of amyloid-β oligomer-activated microglia into the striatum of naïve mice was sufficient to generate all the features of Alzheimer's disease, including widespread tauopathy and synucleinopathy, gliosis, neuroinflammation, synapse loss, neuronal death, and cognitive and motor deficits. These pathological features were eliminated by microglia depletion and anti-inflammatory drug administration. Our results suggest the crucial roles of microglia-driven inflammation in development of mixed pathology. This study provides not only mechanistic insights into amyloid-β oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Developmental trajectories of clinical skills in training physicians vary among tasks and show interindividual differences. This study examined the predictors of medical internship performance and residency entrance and found subtypes of performance trajectory in training physicians., Methods: This retrospective cohort study involved 888 training physicians who completed a medical internship between 2015 and 2019. After the internship, 627 physicians applied for residency training between 2016 and 2020. Finally, 160 of them completed their first-year residency in internal medicine, surgery, pediatrics, and psychiatry departments between 2016 and 2020. Pearson's correlation coefficients of internship performance and first year-residency performance (n = 160) were calculated. Latent profile analysis identified performance trajectory subtypes according to medical school grade point average (GPA), internship performance, English proficiency, and residency selection procedures. Multivariate logistic regression models of residency acceptance (n = 627) and performance in the top 30%/lower 10% in the first year of residency were also constructed., Results: Medical internship performance showed a significant positive correlation with the medical school GPA ( r = 0.194) and the written score for the medical licensing examination ( r = 0.125). Higher scores in the interview (adjusted odds ratio [aOR], 2.57) and written examination (aOR, 1.45) of residency selection procedures and higher medical internship performance (aOR, 1.19) were associated with a higher chance of residency acceptance. The latent profile analyses identified three training physician subgroups: average performance, consistently high performance (top 30%), and adaptation to changes (lowest 10%). Higher scores in the interview for residency selection (aOR, 1.35) and lower scores for medical internship performance (aOR, 0.79) were associated with a higher chance of performing in the top 30% or lowest 10% in the first year of residency, respectively., Conclusion: Performance in the interview and medical internship predicted being among the top 30% and lowest 10% of performers in the first year of residency training, respectively. Individualized educational programs to enhance the prospect of trainees becoming high-functioning physicians are needed., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: A sub-analysis of the Korean population in the LIBERTY ASTHMA QUEST trial (NCT02414854) revealed that dupilumab effectively treated severe uncontrolled asthma. This study aimed to assess the cost-effectiveness of add-on therapy with dupilumab to background therapy in patients ≥ 12 years of age with uncontrolled severe asthma compared to that of background therapy in South Korea., Methods: The cost-effectiveness analysis was conducted using a Markov model over a lifetime from the Korean healthcare system perspective. Clinical efficacy and utility weights were obtained from post-hoc analyses of the Korean population in the QUEST trial. Data on the costs and treatment setting of exacerbation in a real-world setting were retrospectively collected using the administrative medical database from a single tertiary hospital., Results: The base-case results indicated that add-on dupilumab therapy increases costs ($112,924 for add-on dupilumab versus $29,545 for background therapy alone). However, add-on dupilumab increased quality-adjusted life years (QALYs, 8.03 versus 3.93, respectively), with fewer events of severe exacerbations per patient compared to using the background therapy alone (17.920 versus 19.911, respectively). The incremental cost-effectiveness ratio was $20,325 per QALY. Various sensitivity analyses supported the robustness of the base-case results. Probabilistic sensitivity analysis showed that the probability of add-on dupilumab being cost-effective was 87% at a threshold willingness-to-pay of $26,718 (KRW 35 million) per QALY gained., Conclusions: Dupilumab is cost-effective for adolescents and adults with uncontrolled severe asthma in South Korea. Our study provides evidence to support clinicians and policymakers in making informed decisions for severe asthma management., (© 2024. The Author(s).)

Skeletal disorders, including fractures, osteoporosis, osteoarthritis, rheumatoid arthritis, and spinal degenerative conditions, along with associated spinal cord injuries, significantly impair daily life and impose a substantial burden. Many of these conditions are notably linked to inflammation, with some classified as inflammatory diseases. Pyroptosis, a newly recognized form of inflammatory cell death, is primarily triggered by inflammasomes and executed by caspases, leading to inflammation and cell death through gasdermin proteins. Emerging research underscores the pivotal role of pyroptosis in skeletal disorders. This review explores the pyroptosis signaling pathways and their involvement in skeletal diseases, the modulation of pyroptosis by other signals in these conditions, and the current evidence supporting the therapeutic potential of targeting pyroptosis in treating skeletal disorders, aiming to offer novel insights for their management.

Our recent studies have identified p21-activated kinase 4 (PAK4) as a key regulator of lipid catabolism in the liver and adipose tissue, but its role in glucose homeostasis in skeletal muscle remains to be explored. In this study, we find that PAK4 levels are highly upregulated in the skeletal muscles of diabetic humans and mice. Skeletal muscle-specific Pak4 ablation or administering the PAK4 inhibitor in diet-induced obese mice retains insulin sensitivity, accompanied by AMPK activation and GLUT4 upregulation. We demonstrate that PAK4 promotes insulin resistance by phosphorylating AMPKα2 at Ser491, thereby inhibiting AMPK activity. We additionally show that skeletal muscle-specific expression of a phospho-mimetic mutant AMPKα2 S491D impairs glucose tolerance, while the phospho-inactive mutant AMPKα2 S491A improves it. In summary, our findings suggest that targeting skeletal muscle PAK4 may offer a therapeutic avenue for type 2 diabetes., (© 2024. The Author(s).)

Skeletal muscle atrophy, characterized by diminished muscle strength and mass, arises from various causes, including malnutrition, aging, nerve damage, and disease-related secondary atrophy. Aging markedly escalates the prevalence of sarcopenia. Concurrently, the incidence of muscle atrophy significantly rises among patients with chronic ailments such as heart failure, diabetes, and chronic obstructive pulmonary disease (COPD). Epigenetics plays a pivotal role in skeletal muscle atrophy. Aging elevates methylation levels in the promoter regions of specific genes within muscle tissues. This aberrant methylation is similarly observed in conditions like diabetes, neurological disorders, and cardiovascular diseases. This study aims to explore the relationship between epigenetics and skeletal muscle atrophy, thereby enhancing the understanding of its pathogenesis and uncovering novel therapeutic strategies.

Background: This study aimed to investigate quality of life (QoL) in middle-aged adults living alone and identify comprehensive biological, psychological, interpersonal, and contextual factors related to QoL using the dynamic biopsychosocial model. As a secondary analysis, this study used data from the 2017 Korea Community Health Survey conducted by the Korea Disease Control and Prevention Agency., Methods: Among the total 228,381 respondents, 10,639 middle-aged individuals aged 40-64 years from single-person households (5,036 men and 5,603 women) were included in the analysis. QoL was measured using the EuroQoL-5 Dimension (EQ-5D). The EQ-5D descriptive statistics were provided according to biological, psychological, interpersonal, and contextual factors. Considering the data structure of the multistage stratified cluster sampling method, a complex samples general linear model statistic was used to identify the predictors of QoL., Results: QoL was lower in those who had undesirable psychological status (e.g., more depressive symptoms, poor subjective health, and higher perceived stress), less engagement in social networking (less frequent contact with friends and less frequent participation in social activities such as religious activities, friendship gathering, and leisure), and lower physical, behavioral, and socioeconomic factors., Conclusions: This study's findings indicate that psychological and interpersonal factors should be addressed and prioritized to improve the QoL of middle-aged adults living alone. By providing many opportunities for easily accessible social activities that meet the needs and interests of this demographic, their QoL can be improved through strengthening social support., (© 2024. The Author(s).)

A recent study by Kumar et al. identified several biological pathways that regulate the levels of endogenous alpha-synuclein (α-synuclein). They specifically highlighted the N-terminal acetylation (NTA) pathway as an important factor in maintaining the stability of endogenous α-synuclein, suggesting targeting the NTA pathway as a potential therapeutic approach., Competing Interests: Declaration of interests S-J.L. is a cofounder and CEO of Neuramedy Co. Ltd. E-J.B. declares no competing interests in relation to this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Coronary artery complications (CACs) in patients who undergoing prosthetic pulmonary valve implantation for congenital heart disease can lead to fetal outcomes. However, the incidence of and risk factors for CACs in these patients remain unknown., Methods and results: A retrospective cohort study was conducted on patients who underwent cardiac computed tomography or invasive coronary angiography after prosthetic pulmonary valve implantation at Seoul National University Hospital from June 1986 to May 2021. Among 341 patients, 25 (7.3%) were identified with CACs, and 2 of them died. Among the patients with CACs, congenital coronary anomalies and an interarterial course of the coronary artery were identified in 11 (44%) and 18 (72%) patients, respectively. Interarterial and intramural courses of the coronary artery were associated with a 4.4- and 10.6-fold increased risk of CACs, respectively. Among patients with tetralogy of Fallot and pulmonary atresia, the aortic root was rotated further clockwise in patients with coronary artery compression compared to those without it (mean [±SD] 128.0±19.9° vs. 113.5±23.7°; P=0.024). The cut-off rotation angle of the aorta for predicting the occurrence of coronary artery compression was 133°., Conclusions: Perioperative coronary artery evaluation and prevention of CACs are required in patients undergoing prosthetic pulmonary valve implantation, particularly in those with coronary artery anomalies or severe clockwise rotation of the aortic root.

Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson's correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach's α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.

Scope: Cannabidiol (CBD), the most abundant non-psychoactive constituent of the plant Cannabis sativa, is known to possess immune modulatory properties. This study investigates the effects of CBD on mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice., Methods and Results: Mouse bone marrow-derived mast cells and human cord-blood derived mast cells are generated. CBD suppressed antigen-stimulated mast cell degranulation in a concentration-dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long-term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells., Conclusion: Based on these results, the administration of CBD is a new therapeutic intervention in mast cell-associated anaphylactic diseases., (© 2023 Wiley-VCH GmbH.)

Parkinson disease (PD) characterized by dopaminergic neuronal loss is caused by aggregation of misfolded SNCA/α-synuclein. We recently developed autophagy-targeting chimera (AUTOTAC), a targeted protein degradation (TPD) technology based on the macroautophagy/autophagy-lysosome pathway (ALP). In this study, we employed AUTOTAC to synthesize ATC161, a chimeric compound that adopts Anle138b as target-binding ligand (TBL) for SNCA aggregates. The autophagy-targeting ligand (ATL) of ATC161 was designed to allosterically activate the autophagy receptor SQSTSM1/p62 (sequestosome 1), a key step for targeting SNCA aggregates to the phagophore. The lysosomal degradation of SNCA aggregates by ATC161 acutely occurs at DC50 of 100-500 nM with no significant off-target degradation of monomeric SNCA. ATC161 protects cells from DNA and mitochondrial damage by SNCA aggregates. In PD model mice, oral administration of ATC161 decreases the level of SNCA aggregates and their propagation across brain regions, which mitigates glial inflammatory responses and improves muscle strength and locomotive activity. An Investigational New Drug (IND) was approved by the Korean Food and Drug Administration for a phase 1 clinical trial to treat PD, Alzheimer disease (AD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS). We suggest that AUTOTAC provides a platform for drug discovery in proteinopathies and other diseases.

Objectives: The aim of this study is to evaluate the accuracy of zirconia crowns fabricated using stereolithography (SLA) and digital light processing (DLP) and to compare their accuracy with those fabricated using the subtractive manufacturing (SM) method., Methods: A typodont model with a prepared maxillary first molar was scanned, and the anatomical contour crown was designed using dental computer-aided-design (CAD) software. The designed file in standard tessellation language (STL) format was used to fabricate 10 crowns per group. The crowns were manufactured using a dental milling machine (Datron D5; MLC group), SLA (CERAMAKER 900; SLAC group), and DLP (ZIPRO; DLPC group) printers. The fabricated crowns were scanned using a dental laboratory scanner and saved in three parts: the external, intaglio, and marginal surfaces. For accuracy assessment, these parts were superimposed to the reference file. Root mean square (RMS) values were evaluated using three-dimensional analysis software (Geomagic Control X). Statistical significance was evaluated using a nonparametric Kruskal-Wallis test (α = 0.05) and a post-hoc Mann-Whitney U test with Bonferroni correction (α = 0.016)., Results: Trueness evaluation revealed the lowest RMS value in all areas in the MLC group, followed by that in the DLPC group. The precision evaluation revealed the lowest RMS value in all areas in the MLC group. Statistically significant differences were observed among the groups in the external, intaglio, and marginal surface (P < 0.05)., Conclusions: Although the restorations fabricated using SM revealed higher accuracy, the crowns manufactured using SLA and DLP methods were considered clinically acceptable., Clinical Significance: In the production of zirconia crowns, subtractive manufacturing continues to demonstrate significantly higher accuracy compared to additive manufacturing. However, crowns fabricated using the additive manufacturing method also demonstrated high accuracy., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Midaortic syndrome (MAS) presents challenges in diagnosis due to the absence of well-defined diagnostic criteria in pediatric patients. This retrospective study aimed to aid in the diagnosis of MAS by employing computed tomography (CT) to measure the z-score of the aorta as well as to identify and understand its clinical features. CT images, echocardiography findings, and medical records of 17 patients diagnosed with MAS between 1997 and 2023 were reviewed, and z-scores were calculated. Aortic size on follow-up CT, blood pressure, and left ventricular function and hypertrophy at the last follow-up were analyzed, and possible prognostic factors were examined. Except for one patient, all individuals exhibited a z-score below - 2 at the level corresponding to stenosis. Left ventricular dysfunction occurred more frequently in patients aged < 5 years (p = 0.024). Patients with idiopathic MAS showed a better prognosis in terms of blood pressure and follow-up aortic size (p = 0.051 and 0.048, respectively). CT-measured aortic z-scores may be useful for the diagnosis and follow-up of MAS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adipose tissue lipolysis is mediated by cAMP-protein kinase A (PKA)-dependent intracellular signalling. Here, we show that PKA targets p21-activated kinase 4 (PAK4), leading to its protein degradation. Adipose tissue-specific overexpression of PAK4 in mice attenuates lipolysis and exacerbates diet-induced obesity. Conversely, adipose tissue-specific knockout of Pak4 or the administration of a PAK4 inhibitor in mice ameliorates diet-induced obesity and insulin resistance while enhancing lipolysis. Pak4 knockout also increases energy expenditure and adipose tissue browning activity. Mechanistically, PAK4 directly phosphorylates fatty acid-binding protein 4 (FABP4) at T126 and hormone-sensitive lipase (HSL) at S565, impairing their interaction and thereby inhibiting lipolysis. Levels of PAK4 and the phosphorylation of FABP4-T126 and HSL-S565 are enhanced in the visceral fat of individuals with obesity compared to their lean counterparts. In summary, we have uncovered an important role for FABP4 phosphorylation in regulating adipose tissue lipolysis, and PAK4 inhibition may offer a therapeutic strategy for the treatment of obesity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: To investigate cardiovascular characteristics and progressions of hypertrophic cardiomyopathy (HCM) and pulmonary stenosis (PS) and determine whether any genotype-phenotype correlations exist in patients with gene-confirmed RASopathy syndrome., Study Design: Eighty patients (male, 55%) confirmed as having RASopathy syndrome by genetic testing at a single tertiary center were enrolled. Subjects' medical and echocardiography records were reviewed and the changes in the z scores of left ventricular wall thickness (LVWT) and the degree of PS over time were examined during follow-up of 5.7 ± 3.1 and 7.5 ± 5.2 years, respectively., Results: The most common RASopathy gene identified was PTPN11 (56%), followed by RAF1 (10%). Eighty-five percent of patients had cardiovascular diseases, wherein 42% had HCM, and 38% PS. Mean maximal LVWT z score on the initial echocardiography (mean age 5.0 ± 6.0 years) was 3.4 ± 1.3 (median 2.8, range 2.1-6.6) in the HCM group. Overall, the maximal LVWT increased with time, especially in the HCM group (z = 3.4 ± 1.3 to 3.7 ± 1.6, P = .008) and RAF1-variant group (z = 3.7 ± 1.7 to 4.6 ± 1.8, P = .031). Five patients newly developed HCM during the study period. Genotype-phenotype correlation was significant for HCM (P = .002); 31% of patients with PTPN11 and 88% with RAF1 variants had HCM. PS did not progress in this study cohort., Conclusions: In this study, progression of ventricular hypertrophy was seen in a significant number of patients with genotype correlation. Thus, long-term follow up of cardiovascular problems in patients with RASopathy is necessary., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sargent's cherry trees ( Prunus sargentii Rehder) are widely planted as an ornamental, climate change-sensing species. This study investigated changes in the soil moisture content, fresh weight, photosynthesis and chlorophyll fluorescence properties, and the chlorophyll and proline content of four-year-old P. sargentii seedlings after 30 days of drought stress. In the trees subjected to drought stress treatment, soil moisture content decreased, and the fresh weight of the aboveground part of the plant decreased. However, there was no significant difference in the root growth of the dried plants. Among the photosynthesis parameters, P n MAX , E and g s showed a significant ( p   <  0.001) decrease after 15 days in dry-stressed seedlings, but there was no difference between treatments in WUE until 20 days, and there was a significant ( p   <  0.001) difference after 24 days. Chlorophyll fluorescence parameters, F v /F m , ΦPSII, R fd , NPQ, and P n MAX, also increased after 10 days in dry-stressed seedlings, but these changes did not reach statistical significance compared to the control treatment. These results may suggest that drought stress highly correlates with photosynthesis and chlorophyll fluorescence parameters. Chlorophyll content also significantly decreased in the seedlings under drought stress compared with the control treatment. The proline content decreased until the 10th day of drought stress treatment and increased after the 15th day, showing an increase of 10.9% on the 15th day and 57.1% on the 30th day, compared to the control treatment. These results suggest that photosynthesis, chlorophyll fluorescence parameters, and proline content can be used to evaluate drought stress in trees. The results of this study can contribute to the management of forests, such as the irrigation of trees when pore control ability and photosynthesis ability decrease., Competing Interests: The authors declare there are no competing interests., (©2023 Jin et al.)

Parkinson's disease (PD) is characterized by a selective loss of dopaminergic neurons. While most research on PD conducted to date has focused on neurons and, to a certain extent, glia, few studies have investigated changes in oligodendroglia. Here, we investigated the heterogeneity of oligodendrocytes from PD patients compared with those of control cases by analyzing single-nuclei transcriptomes. These analyses revealed the presence of distinct oligodendrocyte populations in PD patients indicative of corresponding variations in molecular features, notably including activation of inflammatory responses, response to protein folding stress, and myelination abnormalities. We confirmed myelination abnormalities in an α-synuclein preformed fibril-injection mouse model of PD. These results suggest that oligodendrocytes acquire disease-associated phenotypes in PD and may contribute to the accompanying neurodegeneration., (© 2023. Min Zhuo, Bong-Kiun Kaang and BioMed central Ltd.)

We report the electroluminescence (EL) characteristics of blue ultra-thin emissive layer (U-EML) phosphorescent (PH) organic light-emitting diodes (OLED) and thermally activated delayed fluorescence (TADF) OLED. A variety of transport layer (TL) materials were used in the fabricated OLEDs. The well-known FIrpic and DMAC-DPS were used with a thickness of 0.3 nm, which is relatively thicker than the optimal thickness (0.15 nm) of the blue phosphorescent ultra-thin emissive layer to ensure sufficient energy transfer. While FIrpic showed overall high efficiency in various TLs, DMAC-DPS exhibited three times lower efficiency in limited TLs. To clarify/identify low efficiency and to improve the EL, the thickness of DMAC-DPS was varied. A significantly higher and comparable efficiency was observed with a thickness of 4.5 nm, which is 15 times thicker. This thickness was oriented from the TADF itself, which reduces quenching in a triplet-triplet annihilation compared to the PH process. The thinner optimal thickness compared with ~30 nm of fluorescent OLEDs suggests that there still is quenching taking place. We expect that the efficiency of TADF U-EML OLEDs can be enhanced through further research on controlling the exciton quenching using multiple U-EMLs with spacers and a novel material with a high energy transfer rate (ΔE S-T ).

In this study, various diffusers are applied to highly efficient ultra-thin emission layer (EML) structure-based blue phosphorescent organic light-emitting diodes (PHOLEDs) to improve the electroluminescence (EL) characteristics and viewing angle. To achieve highly efficient blue PHOLEDs, the EL characteristics of ultra-thin EML PHOLEDs with the various diffusers having different structures of pattern-shape (hemisphere/sphere), size (4~75 μm), distribution (surface/embedded), and packing (close-packed/random) were systematically analyzed. The diffusers showed different enhancements in the overall EL characteristics of efficiencies, viewing angle, and others. The EL characteristics showed apparent dependency on their structure. The external quantum efficiency (EQE) was enhanced mainly by following the orders of pattern, size, and shape. Following the pattern size, the EQE enhancement gradually increased; the largest-sized diffuser with a 75 μm closed-packed hemisphere (diffuser-1) showed a 1.47-fold EQE improvement, which was the highest. Meanwhile, the diffuser with a ~7 μm random embedded sphere with a low density (diffuser 5) showed the lowest 1.02-fold-improved EQE. The reference device with ultra-thin EML structure-based blue PHOLEDs showed a maximum EQE of 16.6%, and the device with diffuser 1 achieved a maximum EQE of 24.3% with a 5.1% wider viewing angle compared to the reference device without a diffuser. For the in-depth analysis, the viewing angle profile of the ultra-thin EML PHOLED device and fluorescent green OLEDs were compared. As a result, the efficiency enhancement characteristics of the diffusers show a difference in the viewing angle profile. Finally, the application of the diffuser successfully demonstrated that the EL efficiency and viewing angle could be selectively improved. Additionally, we found that it was possible to realize a wide viewing angle and achieve considerable EQE enhancement by further investigations using high-density and large-sized embedded structures of light-extraction film.

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis., (© 2023. Springer Nature Limited.)

This study investigates the application of scattering structures to the metal layer in a DMD (Dielectric/Metal/Dielectric) configuration through plasma treatment. The purpose is to enhance the light extraction efficiency of organic light-emitting diodes (OLEDs). Different plasma conditions were explored to create scattering structures on the metal layer. The fabricated devices were characterized for their electrical and optical properties. The results demonstrate that the introduction of scattering structures through plasma treatment effectively improves the light extraction efficiency of OLEDs. Specifically, using O 2 -plasma treatment on the metal layer resulted in significant enhancements in the total transmittance, haze, and figure of merit. These findings suggest that incorporating scattering structures within the DMD configuration can effectively promote light extraction in OLEDs, leading to enhanced overall performance and light efficiency.

In this study, we demonstrated organic light-emitting diodes (OLEDs) outcoupling with a flexible polydimethylsiloxane (PDMS) film with a micro-convex structure using the breath figure (BF) method. We can easily control the micro-convex pattern by adjusting the concentration of polystyrene and the humidity during the BF process. As process conditions to fabricate the micro-convex structure, polymer concentrations of 10, 20, 40, and 80 mg/mL and 60, 70, and 80% relative humidity were used. To evaluate the optical properties, we analyzed the transmission, diffusion, and electroluminescence with or without the micro-convex structure on the OLEDs. The shape and density of the micro-convex structure are related to its optical properties and outcoupling and we have experimentally demonstrated this. By applying a micro-convex structure, it achieved up to a 42% improvement in the external quantum efficiency compared to bare OLEDs (without any light extraction film). We expect the fabricated flexible light extraction film to be effective for outcoupling and applicable to flexible devices.

Background: The rate of the prenatal diagnosis of congenital heart disease is increasing along with advances in fetal echocardiography techniques. Here, we aimed to investigate the trend of the use of fetal echocardiography over time and to compare the medical costs of congenital heart disease treatment according to whether fetal echocardiography was performed., Methods: We reviewed our hospital's database, and patients who underwent the first surgery for congenital heart disease within 30 days of birth during 2005-2007, 2011-2013, and 2017-2019 were included. The severity of congenital heart disease diagnosed in each case was evaluated according to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Scores (STS-EACTS Mortality Scores) and Mortality Categories (STAT Mortality Categories)., Results: In total, 375 patients were analyzed, and fetal echocardiography use increased significantly after the 2010s compared with in 2005-2007 (19.1% vs. 39%, p  = 0.032 in Mortality Category 1-3; 15.5% vs. 69.5%, p  = 0.000 in Mortality Category 4-5). Additionally, the mean STS-EACTS Mortality Score was higher in prenatally diagnosed patients than in postnatally diagnosed patients (2.287 vs. 1.787, p  = 0.001). In the recent period, there was no significant difference in hospitalization durations and medical costs according to whether or not fetal echocardiography was performed., Conclusions: This single center study showed the use of fetal echocardiography is increasing. Further, prenatal diagnosis with fetal echocardiography causing no differences in medical costs in recent years. Therefore, we suggest that fetal echocardiography can be applied more widely without increasing the economic burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Choi, Song, Lee, Kim, Bae, Park, Jun, Kwon, Lim and Kim.)

Background: There are currently no disease-modifying therapeutics for Parkinson's disease (PD). Although extensive efforts were undertaken to develop therapeutic approaches to delay the symptoms of PD, untreated α-synuclein (α-syn) aggregates cause cellular toxicity and stimulate further disease progression. PROTAC (Proteolysis-Targeting Chimera) has drawn attention as a therapeutic modality to target α-syn. However, no PROTACs have yet shown to selectively degrade α-syn aggregates mainly owing to the limited capacity of the proteasome to degrade aggregates, necessitating the development of novel approaches to fundamentally eliminate α-syn aggregates., Methods: We employed AUTOTAC (Autophagy-Targeting Chimera), a macroautophagy-based targeted protein degradation (TPD) platform developed in our earlier studies. A series of AUTOTAC chemicals was synthesized as chimeras that bind both α-syn aggregates and p62/SQSTM1/Sequestosome-1, an autophagic receptor. The efficacy of Autotacs was evaluated to target α-syn aggregates to phagophores and subsequently lysosomes for hydrolysis via p62-dependent macroautophagy. The target engagement was monitored by oligomerization and localization of p62 and autophagic markers. The therapeutic efficacy to rescue PD symptoms was characterized in cultured cells and mice. The PK/PD (pharmacokinetics/pharmacodynamics) profiles were investigated to develop an oral drug for PD., Results: ATC161 induced selective degradation of α-syn aggregates at DC 50 of ~ 100 nM. No apparent degradation was observed with monomeric α-syn. ATC161 mediated the targeting of α-syn aggregates to p62 by binding the ZZ domain and accelerating p62 self-polymerization. These p62-cargo complexes were delivered to autophagic membranes for lysosomal degradation. In PD cellular models, ATC161 exhibited therapeutic efficacy to reduce cell-to-cell transmission of α-syn and to rescue cells from the damages in DNA and mitochondria. In PD mice established by injecting α-syn preformed fibrils (PFFs) into brain striata via stereotaxic surgery, oral administration of ATC161 at 10 mg/kg induced the degradation of α-syn aggregates and reduced their propagation. ATC161 also mitigated the associated glial inflammatory response and improved muscle strength and locomotive activity., Conclusion: AUTOTAC provides a platform to develop drugs for PD. ATC161, an oral drug with excellent PK/PD profiles, induces selective degradation of α-syn aggregates in vitro and in vivo. We suggest that ATC161 is a disease-modifying drug that degrades the pathogenic cause of PD., (© 2023. The Author(s).)

In South Korea, the ready-to-use hexavalent vaccine (against diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis B) is not listed despite its facility of no need to reconstitute. It, therefore, has the potential to augment the efficiency of prevention against the six infectious diseases, and it may reduce vaccine-related errors of reconstitution when compared with the currently used vaccination scheme of the pentavalent vaccine with the additional shots against hepatitis B. Given the assumed clinical equivalence between the two vaccination schemes, a cost-minimization analysis has been performed from a societal perspective including all the medical and non-medical direct and indirect costs when vaccinating one birth cohort. The results indicate that the ready-to-use hexavalent vaccine induces a cost reduction of KRW 47,155 (USD36.22) per infant or 12,026 million Korean Won ($9,236,417) in total for the whole birth cohort with 260,500 children. Using the ready-to-use hexavalent vaccine causes a lower infection rate, has fewer vaccination sessions, and may save much time as compared with the current vaccination scheme in place. The ready-to-use hexavalent vaccine may, therefore, benefit the National Immunization Program by reducing the total societal costs of vaccination while improving convenience of infants, parents, and medical care professionals.

Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells' point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

Given the serious consequences of unhealthy weight control behaviors (UWCB) among adolescents, identifying factors contributing to it in this population is crucial. Although gender differences have been reported as UWCB-related factors, studies on weight status remain limited. Hence, using a nationally representative sample, we investigated the differences in UWCB-related factors by gender and weight status. Most sociodemographic, health-related behavior, psychosocial, and school factors were remarkably correlated with UWCB in the normal-weight female group; however, they demonstrated most inconsistent correlations in the overweight female group. Overall, this study suggests that UWCB-preventing interventions in adolescents should be customized by gender and weight status., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Around 80% of the patients who developed advanced PCa suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the detailed mechanisms underlying castration-resistant PCa (CRPC) remain unclear. Sirtuin 5 (SIRT5), an NAD + -dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we revealed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patient's reduced survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase in the succinylation at lysine 118 (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study reveals the reduction of SIRT5 protein expression and LDHA-K118su as a novel mechanism involved in PCa progression, which could serve as a new target to prevent CPRC progression for PCa treatment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To elucidate the experiences of school nurses when responding to public health crises in Korea., Design: Phenomenological research., Methods: One-on-one online in-depth interviews were conducted (N = 10)., Findings: Major public health crises considerably affected schools, school nurses, and the revision of the School Health Act., Conclusions: The experiences of school nurses in responding to periodic public health crises over the few decades have contributed to the advancement of an infectious disease response system in schools., Clinical Evidence: The activities of school nurses during public health crises could serve as a foundation to improve the system.

Background and Objectives: Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure. However, in pediatric and congenital heart disease (CHD) patients, current adult indications cannot be directly applied because of heterogeneity in anatomy and diagnosis. Therefore, CRT responses and clinical outcomes in these patients were investigated to derive possible candidates for CRT., Methods: This study retrospectively analyzed 16 pediatric and CHD patients who underwent CRT implantation at a single center in early (0.7±0.2 year) and late (4.7±0.3 years) follow-up period after CRT., Results: The median age at CRT implantation was 2.5 (0.3-37.2) years, and median follow-up duration was 6.3 (0.1-13.6) years. Thirteen had non-transvenous CRT. Two had congenital complete atrioventricular (AV) block with previous right ventricular pacing, 5 had dilated cardiomyopathy (DCM) with left bundle branch block, and 9 had CHD. The mean ejection fraction of the systemic ventricle increased from 28.1±10.0% to 44.3±21.0% (p=0.003) in early and 51.8±16.3% (p=0.012) in late outcome. The mean functional class improved from 3.1±0.9 to 1.8±1.1 after CRT (p=0.003). Twelve patients (75%) showed improvement in ventricular function or functional class after CRT. Proportion of responders differed between patients without CHD (2/2 patients with complete AV block and 5/5 with DCM, 100%) and those with CHD (5/9, 56%), although statistical significance was not reached (p=0.088)., Conclusions: CRT improved ventricular function and functional status according to the underlying condition in pediatric and CHD patients. However, further large and longer-term studies are needed to establish the guideline for the patient selection of CRT in these patients., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022. The Korean Society of Cardiology.)

p21-Activated kinase 4 (PAK4), one of the serine/threonine kinases activated by Rho-family GTPases, has been widely studied as an oncogenic protein that is overexpressed in many types of cancers. In our recent study, PAK4 upregulation was observed in mice exhibiting hepatic ischaemia-reperfusion (I/R) and in liver transplantation patients. Liver I/R injury was also attenuated in Pak4 KO mice. Herein, we report a novel series of pyrazolo[3,4- d ]pyrimidine derivatives of type I ½ PAK4 inhibitors. The most potent compound SPA7012 was evaluated to determine the pharmacological potential of PAK4 inhibitor in I/R injury in mice. Mice with I/R injury showed typical patterns of liver damage, as demonstrated by increases in serum levels of aminotransferases and proinflammatory cytokines, hepatocellular necrosis and apoptosis, and inflammatory cell infiltration, relative to sham mice. Conversely, intraperitoneal administration of SPA7012 dramatically attenuated biochemical and histopathologic changes. Mechanistically, stabilisation of nuclear factor-erythroid 2-related factor 2 (Nrf2), a master regulator of anti-oxidative response, was observed following SPA7012 treatment. SPA7012 treatment in primary hepatocytes also attenuated hypoxia-reoxygenation-induced apoptotic cell death and inflammation. Together, these results provide experimental evidence supporting the use of PAK4 inhibitors for alleviation of I/R-induced liver damage.

The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain., (© 2022. The Author(s).)

Purpose: This study aims to investigate the knowledge structure and research trends in child and adolescent health literacy research over the past 30 years by using network text analysis., Method: The study was conducted in four steps: 1) collecting abstracts, 2) keyword extraction and preprocessing, 3) creation of co-occurrence matrix, and 4) text network analysis., Results: As a result of the centrality analysis, the upper-ranked core keywords were "health care," "health behavior," "prevention," "treatment," and "health promotion." In contrast to earlier times, "barrier," "caregiver," "school setting," and "QOL" have recently emerged as core keywords., Conclusions: Over the past 30 years, child and adolescent health literacy has been importantly addressed in both clinical and public health approaches. The results of the current study provide references for future research in child and adolescent health literacy., Implication for Practice and Research: This study suggests the need for additional research on school-based practices that can improve health literacy and for identifying validated and reliable multidimensional health literacy assessment instruments., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: As high-quality health care encompasses patient-centered care, this study used the perceived quality-satisfaction-behavioral intention and structure-process-outcome models to (1) investigate the relationships among patient experience, patient satisfaction, and the willingness to recommend a hospital and (2) estimate the indirect effects of patient satisfaction on the relationship between patient experience and the willingness to recommend a hospital., Methods: A cross-sectional survey design was adopted to investigate data obtained from the Seoul National University Hospital Patient Experience survey administered in 2020. Responses were analyzed from 1555 patients, who had been admitted to the inpatient ward of a tertiary hospital for a period lasting more than 1 day., Results: The path model demonstrated a good fit to the relationships between patient experience, patient satisfaction, and the willingness to recommend the hospital. Patient experience directly influenced patient satisfaction ( β  = 0.659, p  < 0.001) and the willingness to recommend the hospital ( β  = 0.168, p  < 0.001), whereas patient satisfaction had an indirect effect ( β  = 0.418, p  < 0.001) on the relationship between patient experience and the willingness to recommend the hospital., Conclusion: Patient experience is a critical factor that health care systems need to consider for enhancing patient-centeredness, patient satisfaction, and the willingness to recommend a hospital., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

This study explored the relationship between problematic smartphone use and depressive symptoms, peer relationships, and functional somatic symptoms with a representative sample of Korean male and female adolescents using serial multiple mediation models. The results identified the mediating effect of depressive symptoms and peer relationships for males in the association between problematic smartphone use and FSS. The serial mediating effect of the two mediators was also verified in the model for males. However, in the model for females, only depressive symptoms mediated the relationship between problematic smartphone use and FSS. The findings suggest that parents and professionals should assess adolescents with problematic smartphone use for the risk of FSS when depressive symptoms develop. Schools should also provide programs to build positive peer relationships to reduce FSS., Competing Interests: Declaration of competing interest The author(s) declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: Although long QT syndrome (LQTS) is a potentially life-threatening inherited cardiac channelopathy, studies documenting the long-term clinical data of Korean patients with LQTS are scarce., Methods: This retrospective cohort study included 105 patients with LQTS (48 women; 45.7%) from a single tertiary center. The clinical outcomes were analyzed for the rate of freedom from breakthrough cardiac events (BCEs), additional treatment needed, and death., Results: LQTS was diagnosed at a median age of 11 (range, 0.003-80) years. Genetic testing was performed on 90 patients (yield, 71.1%). The proportions of genetically confirmed patients with LQTS types 1, 2, 3, and others were 34.4%, 12.2%, 12.2%, and 12.2%, respectively. In the symptomatic group (n=70), aborted cardiac arrest was observed in 30% of the patients. Treatments included medications in 60 patients (85.7%), implantable cardioverter-defibrillators in 27 (38.6%; median age, 17 years; range, 2-79 years), and left cardiac sympathetic denervation surgery in 7 (10%; median age, 13 years; range, 2-34). The 10-year BCE-free survival rate was 73.2%. By genotype, significant differences were observed in BCEs despite medication (p<0.001). The 10-year BCE-free survival rate was the highest in patients with LQTS type 1 (81.8%) and the lowest in those with multiple LQTS-associated mutations (LQTM). All patients with LQTS survived, except for one patient who had LQTM., Conclusions: Good long-term outcomes can be achieved by using recently developed genetically tailored management strategies for patients with LQTS., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022. The Korean Society of Cardiology.)

Switching myofibers from the fast-glycolytic type to the slow-oxidative type is associated with an alleviation of the symptoms associated with various cardiometabolic diseases. This study investigates the effect of Vitis vinifera Jingzaojing leaf and shoot extract (JLSE), which is rich in phenolic compounds, on the regulation of skeletal muscle fiber-type switching, as well as the associated underlying mechanism. Male C57BL/6N mice were supplemented orally with vehicle or JLSE (300 mg/kg) and subjected to treadmill exercise training. After four weeks, mice in the JLSE-supplemented group showed significantly improved exercise endurance and mitochondrial oxidative capacity. JLSE supplementation increased the expression of sirtuin 6 and decreased Sox6 expression, thereby elevating the number of mitochondria and encouraging fast-to-slow myofiber switching. The results of our experiments suggest that JLSE supplementation reprograms myofiber composition to favor the slow oxidative type, ultimately enhancing exercise endurance.