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.

Depression remains a major public health challenge, particularly when it becomes treatment-resistant. The development and recovery of depression involve complex interactions among biopsychosocial factors. While the treatment of depression is comprehensive, treatment-resistant depression (TRD) often leans heavily on biological interventions. This review advocates for an integrated approach combining pharmacotherapy and psychotherapy, introducing psychodynamic psychopharmacology as a promising alternative. This strategy aims to enhance treatment outcomes by addressing treatment resistance-related psychodynamic factors and fostering a therapeutic alliance. Notably, the framework categorizing treatment resistance into two types and outlining specific management principles holds practical applicability. Investigating this integrated approach may not only deepen our understanding of TRD but also broaden therapeutic options for clinicians.

Objectives: Breast cancer surgery can significantly impact psychological well-being due to changes in body image and concerns about femininity. This study aimed to explore psychological differences between patients who underwent breast reconstruction after surgery and those who did not, identifying subgroups in need of psychological support. Methods: The study included 194 patients who had breast cancer resection at Kyungpook National University Hospital and its Breast Cancer Center from July 2010 to December 2012. Psychological assessments were conducted within a week post-surgery using the Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-Esteem Scale (RSES), and Body Image Scale (BIS). We applied analysis of covariance to adjust for age and performed K-means cluster analysis. Results: The non-reconstruction group (n=126) exhibited significantly higher HADS scores (14.92±6.65 vs. 11.82±5.92, p=0.002), anxiety (7.37±3.64 vs. 5.94±3.24, p=0.008), and depression (7.46±3.56 vs. 5.91±3.44, p=0.007), along with lower self-esteem (27.07±4.83 vs. 28.98±4.25, p=0.016) compared to the reconstruction group (n=68). Cluster analysis identified two subgroups within the non-reconstruction group: one (Cluster 3, n=35, 27.8%) with high BIS scores, anxiety, and low self-esteem, and another (Cluster 4, n=65, 51.6%) with better psychological health. Importantly, BIS emerged as a significant factor for differentiating subgroups solely within the non-reconstruction group. Conclusions Patients who did not undergo breast reconstruction surgery generally demonstrated negative psychological outcomes. However, the cluster analysis revealed two distinctly different subgroups within this population. Approximately one-quarter (27.8%, n=35) displayed high levels of anxiety and depression, low self-esteem, and severe body image concerns, while about half (51.6%, n=65) maintained good psychological health. This underscores the need to identify patients requiring special clinical attention, even within the same treatment group. Body image assessment may be a valuable evaluation tool specifically for patients who did not undergo breast reconstruction surgery.

Purpose: Incidental prostate cancer (IPCa) is frequently discovered during radical cystectomy (RC) for bladder cancer. While small-scale Korean studies have reported IPCa in 36%–50% of cases and clinically significant prostate cancer (sPCa) in up to 20%, large-scale data assessing its oncologic impact remain scarce. Materials and Methods: We retrospectively analyzed 1,358 male patients who underwent RC between June 1996 and January 2024. IPCa was histologically confirmed and classified per the International Society of Urological Pathology (ISUP) system. sPCa was defined as ISUP grade group (GG) ≥2. Kaplan-Meier analyses were conducted to evaluate survival outcomes. Results: IPCa was identified in 240 patients (17.7%), among whom 7.51% had sPCa. The distribution of ISUP GG was: GG1, 53.8%; GG2, 27.9%; GG3, 9.6%; GG4, 2.5%; and GG5, 1.7%. The proportion of sPCa remained stable across 3 time periods (p=0.281). Mean preoperative prostate-specific antigen (PSA) levels significantly differed among GG1, GG2, and GG3+ groups (2.14±2.37, 4.31±6.69, and 5.86±7.66 ng/mL, respectively; p<0.001). Mean patient age also varied significantly (67.99±8.39, 71.54±8.60, and 72.97±5.53 years; p<0.001). After a median follow-up of 44 months, deaths were unrelated to IPCa. Biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL, occurred in 11 patients (4.58%), with rates of 3.10%, 4.48%, and 12.12% in GG1, GG2, and GG3+ groups, respectively. Overall mortality rates across GG groups were similar (33.3%, 34.3%, and 33.3%; p=0.99). Compared to GG1, hazard ratios for overall survival were 1.03 (GG2, p=0.92), 0.87 (GG3, p=0.76), and 1.05 (GG4–5, p=0.89). Conclusion In this large Korean cohort, IPCa and sPCa were frequently detected at rates similar to global reports. Bladder cancer remained the primary determinant of survival. For older patients with elevated PSA, radical cystoprostatectomy may offer added benefit by treating undiagnosed high-risk IPCa.

Background and Objectives: Monocarboxylate transporter 4 (MCT4) transmembrane proteins are encoded by SLC16A3 and control lactate metabolism to promote tumor growth. Materials and Methods: Gene expression of SLC16A3 encoding MCT4 was analyzed in the database of Gene Expression Omnibus. Protein expression of MCT4 was evaluated using immunohistochemical staining in 138 papillary thyroid carcinomas (PTCs) and 21 anaplastic thyroid carcinomas (ATCs). Results: The mRNA expression of SLC16A3 was significantly higher in ATCs compared with PTCs and normal thyroid tissue (p＜0.01, and p＜0.001, respectively). Normal thyroid tissue did not express MCT4 in immunohistochemical staining compared with ATC that was 100% positive for MCT4 protein expression. The MCT4 expression in ATCs was significantly enhanced compared with that in PTC (p＜0.001). Conclusion MCT4 expression is associated with de-differentiation and might be helpful as a biomarker and therapeutic target for thyroid cancer.

Background and Objectives: Monocarboxylate transporter 4 (MCT4) transmembrane proteins are encoded by SLC16A3 and control lactate metabolism to promote tumor growth. Materials and Methods: Gene expression of SLC16A3 encoding MCT4 was analyzed in the database of Gene Expression Omnibus. Protein expression of MCT4 was evaluated using immunohistochemical staining in 138 papillary thyroid carcinomas (PTCs) and 21 anaplastic thyroid carcinomas (ATCs). Results: The mRNA expression of SLC16A3 was significantly higher in ATCs compared with PTCs and normal thyroid tissue (p＜0.01, and p＜0.001, respectively). Normal thyroid tissue did not express MCT4 in immunohistochemical staining compared with ATC that was 100% positive for MCT4 protein expression. The MCT4 expression in ATCs was significantly enhanced compared with that in PTC (p＜0.001). Conclusion MCT4 expression is associated with de-differentiation and might be helpful as a biomarker and therapeutic target for thyroid cancer.

Background and Objectives: Monocarboxylate transporter 4 (MCT4) transmembrane proteins are encoded by SLC16A3 and control lactate metabolism to promote tumor growth. Materials and Methods: Gene expression of SLC16A3 encoding MCT4 was analyzed in the database of Gene Expression Omnibus. Protein expression of MCT4 was evaluated using immunohistochemical staining in 138 papillary thyroid carcinomas (PTCs) and 21 anaplastic thyroid carcinomas (ATCs). Results: The mRNA expression of SLC16A3 was significantly higher in ATCs compared with PTCs and normal thyroid tissue (p＜0.01, and p＜0.001, respectively). Normal thyroid tissue did not express MCT4 in immunohistochemical staining compared with ATC that was 100% positive for MCT4 protein expression. The MCT4 expression in ATCs was significantly enhanced compared with that in PTC (p＜0.001). Conclusion MCT4 expression is associated with de-differentiation and might be helpful as a biomarker and therapeutic target for thyroid cancer.