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.

Background: Cough is a prominent symptom of chronic respiratory diseases, including asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and bronchiectasis (BE). Some patients develop chronic cough (CC), defined as lasting more than 8 weeks, yet its characteristics remain poorly understood. This study aimed to characterize CC across various chronic respiratory diseases using validated cough assessment tools. Methods: The Cough Assessment in Chronic Respiratory Diseases (COASESS) study, a multicenter, prospective cross-sectional study, was conducted at 10 university hospitals. CC was evaluated in terms of intensity (numeric rating scale [NRS]), frequency (cough symptom score [CSS]), and quality of life (using the cough assessment test [COAT] and Leicester cough questionnaire [LCQ]). Cough hypersensitivity was assessed with the cough hypersensitivity questionnaire (CHQ). Data on age, sex, and smoking status were also collected. Results: Among the 303 enrolled patients, 266 with chronic respiratory diseases were included in the analysis. Patients with asthma were younger, predominantly female, and non-smokers, whereas those with COPD and IPF were older males who had previously smoked (p<0.001). Scores for COAT, LCQ, NRS, and CSS showed significant differences across the diseases, with asthma and IPF patients experiencing a greater symptom burden and lower quality of life compared to those with COPD or BE (p<0.001). Although CHQ total scores were similar across groups, asthma patients more frequently reported triggers such as talking and post-nasal drip. Conclusion This study revealed distinct characteristics of CC across different chronic respiratory diseases. Asthma and IPF were associated with a higher symptom burden, and cough hypersensitivity varied depending on the underlying condition. These findings highlight the necessity for disease-specific assessments and management strategies for CC.

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining Stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3-4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management.This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed. Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria. Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50–1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06–4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05–4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10–2.85), without a substantial increase in the risk of decreased renal function. Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Smoking and sodium intake (SI) have been evaluated as risk factors for kidney disease; however, the data are inconsistent. We assessed the association between SI and cotinine-verified smoking status and the risk of albuminuria. Methods: An observational study using the Korea National Health and Nutrition Examination Survey (2008–2011 and 2014– 2018) was performed. We included 37,410 adults with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2. The smoking status was assumed based on the urine cotinine/creatinine ratio (Ucot/Ucrea). SI was estimated from spot urine sodium using the Kawasaki formula. Results: Ucot/Ucrea levels were significantly higher in current smokers (920.22 ± 9.00 ng/mg) than in ex-smokers and nonsmokers (48.31 ± 2.47 and 23.84 ± 1.30 ng/mg) (p < 0.001). Ucot/Ucrea levels were significantly higher in second-hand smokers than in participants without a history of smoking (p < 0.001). Ucot/Ucrea levels were positively associated with SI (p for trend < 0.001). Smoking status was not associated with albuminuria. SI had a linear relationship with albuminuria (p < 0.001). In groups with the highest Ucot/Ucrea levels, the highest SI quartile indicated a significantly higher risk of albuminuria than that in the lowest quartile (risk ratio, 2.22; 95% confidence interval, 1.26–3.92; p = 0.006). The risk of albuminuria was not significant in groups with the lowest and middle tertile adjusted for multiple risk factors. Conclusion: Smokers consume higher dietary sodium and dietary SI was positively related to the risk of albuminuria. Smoking is not associated with albuminuria as a single factor. The risk of albuminuria is the higher in participants with smoking and high SI.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3 to 4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management. This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Background/Aims: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, exacerbated metabolic health issues, and altered lifestyle behaviors. This study examined the sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Methods: Data from the KNHANES VII (2018) and VIII (2019–2021), including 15,499 participants, were analyzed. The study population was stratified by sex, and further subdivisions were conducted based on the timeframe relative to the COVID-19 outbreak. Variables such as age, education level, household income, smoking status, and high-risk drinking were analyzed to assess their influence on the prevalence of metabolic syndrome. Results: The overall prevalence of metabolic syndrome significantly increased from 28.11% before the outbreak to 29.69% after the outbreak. Both males and females reported significant increases in waist circumference and fasting glucose levels. Age and education level differentially influenced the prevalence of metabolic syndrome between the sex. Smoking was significantly associated with increased prevalence in males, whereas high-risk drinking was associated with increased prevalence in males and decreased prevalence in females. Conclusions The COVID-19 pandemic has significantly increased the prevalence of metabolic syndrome with notable sex-specific differences. These findings highlight the need for sex-specific public health interventions to mitigate the impact of the pandemic on metabolic health.