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: Posterior reversible encephalopathy syndrome (PRES) is a rare complication of lung transplantation with poorly understood risk factors and clinical characteristics. This study aimed to examine the occurrence, risk factors, and clinical data of patients who developed PRES following lung transplantation. Methods: A retrospective analysis was conducted on 147 patients who underwent lung transplantation between February 2013 and December 2023. The patients were diagnosed with PRES based on the clinical symptoms and radiological findings. We compared the baseline characteristics and clinical information, including primary lung diseases and immunosuppressive therapy related to lung transplantation operations, between the PRES and non-PRES groups. Results: PRES manifested in 7.5% (n=11) of the patients who underwent lung transplantation, with a median onset of 15 days after operation. Seizures were identified as the predominant clinical manifestation (81.8%, n=9) in the group diagnosed with PRES. All patients diagnosed with PRES recovered fully. Patients with PRES were significantly associated with connective tissue disease-associated interstitial lung disease (45.5% vs. 18.4%, P=0.019, odds ratio=9.808; 95% CI, 1.064–90.386; P=0.044). Nonetheless, no significant variance was observed in the type of immunotherapy, such as the use of calcineurin inhibitors, blood pressure, or acute renal failure subsequent to lung transplantation. Conclusions PRES typically manifests shortly after lung transplantation, with seizures being the predominant initial symptom. The presence of preexisting connective tissue disease as the primary lung disease represents a significant risk factor for PRES following lung transplantation.

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 Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

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: To investigate the clinicopathologic pattern of prostate cancer (PCa) in elderly patients compared with their younger counterparts with a prostate-specific antigen (PSA) level below the low-risk threshold (< 10 ng/mL), which is often a deciding factor for biopsy. Methods: A nationwide database of PCa at the time of biopsy from 2010 to 2020 was constructed from 39 hospitals. Patients were categorized into age groups of < 64 years, 65–69 years, 70–74 years, and ≥ 75 years considering guidelines that recommend PSA testing only for those aged 55–69 years during the study period, the average age of Korean PCa registrants of 70.3 years (2010–2020), and the average life expectancy of Korean males of 80.3 years (2020). Results: The mean ± standard deviation age was 70.3 ± 8.2 years, which was normally distributed (kurtosis = 0.095). Among 14,548 subjects, 54.1%, 39.5%, and 6.4% of them had high-risk disease, intermediate-risk disease, and low-risk disease, respectively. Based on three risk parameters, a marked increase in high-risk cancer was observed in the oldest age group (linear combination, P < 0.001). The same pattern was observed among patients with low-risk disease (PSA < 10 ng/mL), who were divided into PSA tiers as follows: 4–5 ng/mL (P < 0.001), 5–6 ng/mL (P < 0.001), 6–7 ng/mL (P < 0.001), 7–8 ng/mL (P < 0.001), 8–9 ng/mL (P = 0.009), and 9–10 ng/mL (P < 0.001). In all PSA tiers between 4 and 10 ng/mL, multivariate analysis demonstrated a significantly higher prevalence of high-risk cancer in the oldest age group than in the youngest age group. In the lowest tier (4–5 ng/mL), 35.2% of those aged over 75 years had high-risk PCa. Conclusion The older the patient, the more aggressive the PCa. Moreover, there was an increase in high-risk PCa in older males compared with younger males even with a PSA level below the low-risk threshold of 10 ng/mL, suggesting the need to strengthen cancer screening policies in the older population.

Background: To investigate the clinicopathologic pattern of prostate cancer (PCa) in elderly patients compared with their younger counterparts with a prostate-specific antigen (PSA) level below the low-risk threshold (< 10 ng/mL), which is often a deciding factor for biopsy. Methods: A nationwide database of PCa at the time of biopsy from 2010 to 2020 was constructed from 39 hospitals. Patients were categorized into age groups of < 64 years, 65–69 years, 70–74 years, and ≥ 75 years considering guidelines that recommend PSA testing only for those aged 55–69 years during the study period, the average age of Korean PCa registrants of 70.3 years (2010–2020), and the average life expectancy of Korean males of 80.3 years (2020). Results: The mean ± standard deviation age was 70.3 ± 8.2 years, which was normally distributed (kurtosis = 0.095). Among 14,548 subjects, 54.1%, 39.5%, and 6.4% of them had high-risk disease, intermediate-risk disease, and low-risk disease, respectively. Based on three risk parameters, a marked increase in high-risk cancer was observed in the oldest age group (linear combination, P < 0.001). The same pattern was observed among patients with low-risk disease (PSA < 10 ng/mL), who were divided into PSA tiers as follows: 4–5 ng/mL (P < 0.001), 5–6 ng/mL (P < 0.001), 6–7 ng/mL (P < 0.001), 7–8 ng/mL (P < 0.001), 8–9 ng/mL (P = 0.009), and 9–10 ng/mL (P < 0.001). In all PSA tiers between 4 and 10 ng/mL, multivariate analysis demonstrated a significantly higher prevalence of high-risk cancer in the oldest age group than in the youngest age group. In the lowest tier (4–5 ng/mL), 35.2% of those aged over 75 years had high-risk PCa. Conclusion The older the patient, the more aggressive the PCa. Moreover, there was an increase in high-risk PCa in older males compared with younger males even with a PSA level below the low-risk threshold of 10 ng/mL, suggesting the need to strengthen cancer screening policies in the older population.