Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

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.

RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.

Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy typically associated with dismal outcomes. Most patients present with advanced disease, often precluding curative resection. We report a case of intrathyroidal ATC incidentally identified in a 72-year-old male who underwent diagnostic lobectomy for a low-suspicion, predominantly cystic huge thyroid nodule. Final pathology revealed a completely resected, intrathyroidal ATC without extrathyroidal extension. Postoperative imaging showed no evidence of residual or metastatic disease. Based on multidisciplinary discussion, the patient underwent completion thyroidectomy and central neck dissection without adjuvant therapy. No residual malignancy was identified, and the patient remains recurrence-free at six months. This case highlights that early-stage intrathyroidal ATC may present without overt malignant features and can be curatively treated with complete surgical excision. Careful evaluation and multidisciplinary decision-making are essential in managing rapidly enlarging thyroid nodules with atypical features.

RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.