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: Tobacco use has been the leading cause of disease and death in South Korea. Early detection of tobacco use and evidence-based interventions play pivotal roles in facilitating tobacco cessation. Methods: In accordance with the earlier iterations of the Lifetime Health Maintenance Program (2009) and recent recommendations from the United States Preventive Services Task Force (USPSTF; 2021), two themes were chosen for investigation: the identification of and intervention for tobacco use. The USPSTF recommendations were formulated by conducting an overview of reviews. In this study, literature searches and quality assessments of reviews were conducted. Results: The findings highlighted the efficacy of physician-led identification and advising in promoting tobacco cessation, with robust evidence supporting the implementation of behavioral and pharmacological interventions. These interventions significantly increased the likelihood of successful cessation compared with usual care. Digital interventions, such as internet- or mobile-based interventions, showed additive effects for quitting. Conclusion Identification and targeted interventions are essential for tobacco cessation. By leveraging evidencebased strategies and enhancing access to resources, healthcare providers can empower individuals to achieve successful tobacco cessation and improve overall health outcomes.

There is no established treatment for severe fever with thrombocytopenia syndrome (SFTS). However, the potential role of tocilizumab (TCZ) in cytokine storm modulation warrants further investigation. In this study, we aimed to investigate the therapeutic potential of TCZ in adult patients with SFTS and provide valuable insights into the development of effective treatment strategies for this challenging infectious disease by assessing the impact of TCZ on cytokine dynamics and patient outcomes. This prospective longitudinal observational study included adult patients with SFTS at a teaching hospital in Korea between April 2013 and December 2023. Patients with SFTS and interleukin (IL)-6 levels ≥30 ng/mL received TCZ. The 14- and 28-day mortality rates were compared between the TCZ and therapeutic plasma exchange (TPE) groups during the study period. Among the total of 97 patients, the clinical characteristics showed no significant differences between the TCZ (n=10) and TPE groups (n=30). Compared with TPE, TCZ treatment showed a trend towards lower mortality rate (14-day mortality rate: 10.0% vs. 16.7%, p=0.608; 28-day mortality rate:10.0% vs. 20.0%, p=0.480). Both treatments showed the potential to reduce the viral load and IL-6 levels, indicating their efficacy in managing the disease course. TCZ is a potential therapeutic option for SFTS as it modulates IL-6 levels and improves clinical outcomes.

There is no established treatment for severe fever with thrombocytopenia syndrome (SFTS). However, the potential role of tocilizumab (TCZ) in cytokine storm modulation warrants further investigation. In this study, we aimed to investigate the therapeutic potential of TCZ in adult patients with SFTS and provide valuable insights into the development of effective treatment strategies for this challenging infectious disease by assessing the impact of TCZ on cytokine dynamics and patient outcomes. This prospective longitudinal observational study included adult patients with SFTS at a teaching hospital in Korea between April 2013 and December 2023. Patients with SFTS and interleukin (IL)-6 levels ≥30 ng/mL received TCZ. The 14- and 28-day mortality rates were compared between the TCZ and therapeutic plasma exchange (TPE) groups during the study period. Among the total of 97 patients, the clinical characteristics showed no significant differences between the TCZ (n=10) and TPE groups (n=30). Compared with TPE, TCZ treatment showed a trend towards lower mortality rate (14-day mortality rate: 10.0% vs. 16.7%, p=0.608; 28-day mortality rate:10.0% vs. 20.0%, p=0.480). Both treatments showed the potential to reduce the viral load and IL-6 levels, indicating their efficacy in managing the disease course. TCZ is a potential therapeutic option for SFTS as it modulates IL-6 levels and improves clinical outcomes.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

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: Tobacco use has been the leading cause of disease and death in South Korea. Early detection of tobacco use and evidence-based interventions play pivotal roles in facilitating tobacco cessation. Methods: In accordance with the earlier iterations of the Lifetime Health Maintenance Program (2009) and recent recommendations from the United States Preventive Services Task Force (USPSTF; 2021), two themes were chosen for investigation: the identification of and intervention for tobacco use. The USPSTF recommendations were formulated by conducting an overview of reviews. In this study, literature searches and quality assessments of reviews were conducted. Results: The findings highlighted the efficacy of physician-led identification and advising in promoting tobacco cessation, with robust evidence supporting the implementation of behavioral and pharmacological interventions. These interventions significantly increased the likelihood of successful cessation compared with usual care. Digital interventions, such as internet- or mobile-based interventions, showed additive effects for quitting. Conclusion Identification and targeted interventions are essential for tobacco cessation. By leveraging evidencebased strategies and enhancing access to resources, healthcare providers can empower individuals to achieve successful tobacco cessation and improve overall health outcomes.