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: The use of two adjacent radiation beams to treat a lesion that is larger than the maximum field of a machine may lead to higher or lower dose distribution at the junction than expected. Therefore, evaluation of the junction dose is crucial for radiotherapy. Volumetric modulated arc therapy (VMAT) can effectively protect surrounding normal tissues by implementing a complex dose distribution; therefore, two adjacent VMAT fields can effectively treat large lesions. However, VMAT can lead to significant errors in the junction dose between fields if setup errors occur due to its highly complex dose distributions. Methods: In this study, setup errors of ±1, ±3, and ±5 mm were assumed during radiotherapy for treating large lesions in the lower abdomen, and their effects on the treatment dose distribution and target coverage were analyzed using gamma pass rate (GP) and homogeneity index (HI). All studies were performed using a computational simulation method based on our radiation treatment planning software. Results: Consequently, when the setup error was more than ±3 mm, most GP values using a 3%/3-mm criterion decreased by <90%. GP was independent of the direction of the field gap (FG), whereas HI values were relatively more affected by negative values for FG. Conclusions Therefore, the size and direction of setup errors should be carefully managed when performing dual-isocentric VMATs for large targets.

Purpose: The use of two adjacent radiation beams to treat a lesion that is larger than the maximum field of a machine may lead to higher or lower dose distribution at the junction than expected. Therefore, evaluation of the junction dose is crucial for radiotherapy. Volumetric modulated arc therapy (VMAT) can effectively protect surrounding normal tissues by implementing a complex dose distribution; therefore, two adjacent VMAT fields can effectively treat large lesions. However, VMAT can lead to significant errors in the junction dose between fields if setup errors occur due to its highly complex dose distributions. Methods: In this study, setup errors of ±1, ±3, and ±5 mm were assumed during radiotherapy for treating large lesions in the lower abdomen, and their effects on the treatment dose distribution and target coverage were analyzed using gamma pass rate (GP) and homogeneity index (HI). All studies were performed using a computational simulation method based on our radiation treatment planning software. Results: Consequently, when the setup error was more than ±3 mm, most GP values using a 3%/3-mm criterion decreased by <90%. GP was independent of the direction of the field gap (FG), whereas HI values were relatively more affected by negative values for FG. Conclusions Therefore, the size and direction of setup errors should be carefully managed when performing dual-isocentric VMATs for large targets.

Background: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000–5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. Conclusions Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.Level of evidence: IV.

Background: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000–5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. Conclusions Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.Level of evidence: IV.

Many countries have published clinical practice guidelines for appropriate clinical decisions, optimal treatment, and improved clinical outcomes in patients with acute coronary syndrome. Developing guidelines that are specifically tailored to the Korean environment is crucial, considering the treatment system, available medications and medical devices, racial differences, and level of language communication. In 2017, the Korean Society of Myocardial Infarction established a guideline development committee. However, at that time, it was not feasible to develop guidelines, owing to the lack of knowledge and experience in guideline development and the absence of methodology experts. In 2022, the National EvidenceBased Healthcare Collaborating Agency collaborated with a relevant academic association to develop internationally reliable guidelines, with strict adherence to the methodology for evidence-based guideline development. The first Korean acute coronary syndrome guideline starts from the 9 key questions for pharmacotherapy.

Purpose: The use of two adjacent radiation beams to treat a lesion that is larger than the maximum field of a machine may lead to higher or lower dose distribution at the junction than expected. Therefore, evaluation of the junction dose is crucial for radiotherapy. Volumetric modulated arc therapy (VMAT) can effectively protect surrounding normal tissues by implementing a complex dose distribution; therefore, two adjacent VMAT fields can effectively treat large lesions. However, VMAT can lead to significant errors in the junction dose between fields if setup errors occur due to its highly complex dose distributions. Methods: In this study, setup errors of ±1, ±3, and ±5 mm were assumed during radiotherapy for treating large lesions in the lower abdomen, and their effects on the treatment dose distribution and target coverage were analyzed using gamma pass rate (GP) and homogeneity index (HI). All studies were performed using a computational simulation method based on our radiation treatment planning software. Results: Consequently, when the setup error was more than ±3 mm, most GP values using a 3%/3-mm criterion decreased by <90%. GP was independent of the direction of the field gap (FG), whereas HI values were relatively more affected by negative values for FG. Conclusions Therefore, the size and direction of setup errors should be carefully managed when performing dual-isocentric VMATs for large targets.

Purpose: The use of two adjacent radiation beams to treat a lesion that is larger than the maximum field of a machine may lead to higher or lower dose distribution at the junction than expected. Therefore, evaluation of the junction dose is crucial for radiotherapy. Volumetric modulated arc therapy (VMAT) can effectively protect surrounding normal tissues by implementing a complex dose distribution; therefore, two adjacent VMAT fields can effectively treat large lesions. However, VMAT can lead to significant errors in the junction dose between fields if setup errors occur due to its highly complex dose distributions. Methods: In this study, setup errors of ±1, ±3, and ±5 mm were assumed during radiotherapy for treating large lesions in the lower abdomen, and their effects on the treatment dose distribution and target coverage were analyzed using gamma pass rate (GP) and homogeneity index (HI). All studies were performed using a computational simulation method based on our radiation treatment planning software. Results: Consequently, when the setup error was more than ±3 mm, most GP values using a 3%/3-mm criterion decreased by <90%. GP was independent of the direction of the field gap (FG), whereas HI values were relatively more affected by negative values for FG. Conclusions Therefore, the size and direction of setup errors should be carefully managed when performing dual-isocentric VMATs for large targets.

Many countries have published clinical practice guidelines for appropriate clinical decisions, optimal treatment, and improved clinical outcomes in patients with acute coronary syndrome. Developing guidelines that are specifically tailored to the Korean environment is crucial, considering the treatment system, available medications and medical devices, racial differences, and level of language communication. In 2017, the Korean Society of Myocardial Infarction established a guideline development committee. However, at that time, it was not feasible to develop guidelines, owing to the lack of knowledge and experience in guideline development and the absence of methodology experts. In 2022, the National EvidenceBased Healthcare Collaborating Agency collaborated with a relevant academic association to develop internationally reliable guidelines, with strict adherence to the methodology for evidence-based guideline development. The first Korean acute coronary syndrome guideline starts from the 9 key questions for pharmacotherapy.

Background: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000–5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. Conclusions Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.Level of evidence: IV.