Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background: Atopic dermatitis (AD) is a common skin disease with a wide range of symptoms. Due to the rapidly changing treatment landscape, regular updates to clinical guidelines are needed. Objective: This study aimed to update the guidelines for the treatment of AD to reflect recent therapeutic advances and evidence-based recommendations. Methods: The Patient characteristics, type of Intervention, Control, and Outcome framework was used to determine 48 questions related to AD management. Evidence was graded, recommendations were determined, and, after 2 voting rounds among the Korean Atopic Dermatitis Association (KADA) council members, consensus was achieved. Results: This guideline provides treatment guidance on advanced systemic treatment modalities for AD. In particular, the guideline offers up-to-date treatment recommendations for biologics and Janus-kinase inhibitors used in the treatment of patients with moderate to severe AD.It also provides guidance on other therapies for AD, along with tailored recommendations for children, adolescents, the elderly, and pregnant or breastfeeding women. Conclusion KADA’s updated AD treatment guidelines incorporate the latest evidence and expert opinion to provide a comprehensive approach to AD treatment. The guidelines will help clinicians optimize patient-specific therapies.

Background: Atopic dermatitis (AD) is a common skin disease with a wide range of symptoms. Due to the rapidly changing treatment landscape, regular updates to clinical guidelines are needed. Objective: This study aimed to update the guidelines for the treatment of AD to reflect recent therapeutic advances and evidence-based practices. Methods: The Patient characteristics, type of Intervention, Control, and Outcome framework was used to determine 48 questions related to AD management. Evidence was graded, recommendations were determined, and, after 2 voting rounds among the Korean Atopic Dermatitis Association (KADA) council members, consensus was achieved. Results: The guidelines provide detailed recommendations on foundational therapies, including the use of moisturizers, cleansing and bathing practices, allergen avoidance, and patient education. Guidance on topical therapies, such as topical corticosteroids and calcineurin inhibitors, is also provided to help manage inflammation and maintain skin barrier function in patients with AD. Additionally, recommendations on conventional systemic therapies, including corticosteroids, cyclosporine, and methotrexate, are provided for managing moderate to severe AD. Conclusion KADA’s updated AD guidelines offer clinicians evidence-based strategies focused on basic therapies, topical therapies, and conventional systemic therapies, equipping them to enhance quality of care and improve patient outcomes in AD management.

Background: In 2006, the Korean Atopic Dermatitis Association (KADA) working group released the diagnostic criteria for Korean atopic dermatitis (AD). Recently, more simplified, and practical AD diagnostic criteria have been proposed. Objective: Based on updated criteria and experience, we studied to develop and share a consensus on diagnostic criteria for AD in Koreans. Materials and Methods: For the diagnostic criteria, a questionnaire was constructed by searching the English-language literature in MEDLINE and the Cochrane Database of Systematic Reviews. A modified Delphi method composed of 3 rounds of email questionnaires was adopted for the consensus process. Fifty-four KADA council members participated in the 3 rounds of votes and expert consensus recommendations were established. Results: Diagnostic criteria for AD include pruritus, eczema with age-specific pattern, and chronic or relapsing history. Diagnostic aids for AD encompass xerosis, immunoglobulin E reactivity, hand–foot eczema, periorbital changes, periauricular changes, perioral changes, nipple eczema, perifollicular accentuation, and personal or family history of atopy. Conclusion This study streamlined and updated the diagnostic criteria for AD in Korea, making them more practicable for use in real-world clinical field.

Background: Inflammation following stroke is associated with poor outcomes, and the anti-inflammatory effects of neural stem cells (NSCs) have been reported. However, the direct immunomodulatory effects of NSCs in hemorrhagic stroke remain unclear. In the present study, we investigated the anti-inflammatory mechanism of direct co-culture with NSCs on RAW 264.7 cells stimulated by hemolysate. Methods: RAW 264.7 cells were stimulated with the hemolysate for 4 hours to induce hemorrhagic inflammation in vitro. Regarding direct co-culture, RAW 264.7 cells were cultured with HB1.F3 cells for 24 hours in normal medium and stimulated with hemolysate for 4 hours. Inflammatory cell signaling molecules, including cycloxygenase-2 (COX-2), interleukin-1β (IL-1β), and extracellular signal-regulated kinase (ERK), as well as tumor necrosis factor-α (TNF-α), were evaluated. Results: After stimulation with the hemolysate, levels of the inflammatory markers COX-2, IL-1β, and TNF-α were increased in RAW264.7 cells. Inflammatory marker production was reduced in the group subjected to direct co-culture with HB1.F3 in comparison to that in the RAW264.7 group stimulated by the hemolysate. In addition, direct co-culture with HB1.F3 significantly suppressed the phosphorylation of ERK 1/2 in hemolysate-stimulated RAW 264.7 cells. Moreover, treatment of the ERK inhibitor (U0126) suppressed the expression levels of inflammatory markers in hemolysate-stimulated RAW246.7 cells. Conclusion These results demonstrate that direct co-culture with HB1.F3 suppresses inflammation by attenuating the ERK pathway. These findings suggest that direct NSC treatment modulates the inflammatory response in hemorrhagic stroke.

Background: Inflammation following stroke is associated with poor outcomes, and the anti-inflammatory effects of neural stem cells (NSCs) have been reported. However, the direct immunomodulatory effects of NSCs in hemorrhagic stroke remain unclear. In the present study, we investigated the anti-inflammatory mechanism of direct co-culture with NSCs on RAW 264.7 cells stimulated by hemolysate. Methods: RAW 264.7 cells were stimulated with the hemolysate for 4 hours to induce hemorrhagic inflammation in vitro. Regarding direct co-culture, RAW 264.7 cells were cultured with HB1.F3 cells for 24 hours in normal medium and stimulated with hemolysate for 4 hours. Inflammatory cell signaling molecules, including cycloxygenase-2 (COX-2), interleukin-1β (IL-1β), and extracellular signal-regulated kinase (ERK), as well as tumor necrosis factor-α (TNF-α), were evaluated. Results: After stimulation with the hemolysate, levels of the inflammatory markers COX-2, IL-1β, and TNF-α were increased in RAW264.7 cells. Inflammatory marker production was reduced in the group subjected to direct co-culture with HB1.F3 in comparison to that in the RAW264.7 group stimulated by the hemolysate. In addition, direct co-culture with HB1.F3 significantly suppressed the phosphorylation of ERK 1/2 in hemolysate-stimulated RAW 264.7 cells. Moreover, treatment of the ERK inhibitor (U0126) suppressed the expression levels of inflammatory markers in hemolysate-stimulated RAW246.7 cells. Conclusion These results demonstrate that direct co-culture with HB1.F3 suppresses inflammation by attenuating the ERK pathway. These findings suggest that direct NSC treatment modulates the inflammatory response in hemorrhagic stroke.

Objective: Research on fetal mortality due to congenital anomalies is insufficient, particularly that utilizing data specific to South Korea. Thus, we aimed to investigate the characteristics and risk factors for fetal death due to congenital anomalies in Korea. Methods: Fetal deaths registered from 2009-2020 with Statistics Korea were assessed. Fetal charac teristics included gestational age, body weight, sex, and multiple fetuses, while maternal characteri stics included age, educational level, nationality, and place of residence. Risk factors for fetal death were analyzed using simple comparison and logistic regression. Changes in fetal mortality by year were examined using Poisson regression analysis. Results: A total of 37,928 fetal deaths occurred, among which 3,758 were classified as congenital anomaly, 710 as non-congenital anomaly, and 33,460 as unknown cause. Fetal mortality for gesta tional weeks 20 to 27 and ≥28 were 75.3% and 24.7%, respectively. The proportion of congenital anomalies among fetal deaths during these gestational age periods is 11.3% and 5.8%. Multiple fetuses, maternal age of <20 years or ≥40 years were identified as risk factors for fetal death due to congenital anomalies. Among the top 30 causes, covering 97.5% of all deaths, unspecified causes were 88.2%, congenital malformations 8.2%, and other causes 2.0%, respectively. Fetal mortality and deaths from congenital anomalies exhibited downward trends. Conclusion Fetal deaths due to congenital anomalies showed a decreasing trend, but the risks, such as multiple fetuses and advanced maternal age are increasing in Korea. Therefore, careful monitoring of fetal deaths due to congenital anomalies are essential.