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.

The interstitial cells of Cajal (ICC) generate spontaneous pacemaker activities responsible for producing slow waves in the gut smooth muscles. Prostaglandin E2 (PGE2 ) is one of the most important prostanoids in the gut, playing a crucial role in multiple physiological and pathological processes. Because information regarding the effects of PGE2 on colonic ICC is limited, we investigated the effects of PGE2 and its underlying signaling pathways in murine colonic ICC. Whole-cell patch-clamp recordings and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to evaluate the effects of PGE2 on mouse colonic ICC. PGE2 had a dual effect on pacemaker potential in the current-clamp mode. RT-PCR data suggested the expression of EP3 and EP4 receptors in colonic ICC. Low PGE2 concentrations induced membrane depolarization and generation of pacemaker activities. And this effect is mimicked by sulprostone (an EP3 agonist). The low PGE2 concentration-induced effect was inhibited by anoctamin-1 (ANO1) or a T-type Ca2+ channel blocker. Conversely, high PGE2 concentrations induced membrane hyperpolarization and blocked pacemaker potential generation. However, this inhibitory effect was blocked by an ATP-sensitive potassium (K ATP) channel blocker but not by other K+ channel blockers. Low concentrations of PGE2 activated EP3 receptors, leading to excitation of pacemaker activity through regulation of ANO1 and T-type Ca2+ channels in colonic ICC. In contrast, higher concentrations of PGE2 activated EP4 receptors and opened ATP-sensitive K+ channels, resulting in inhibition of pacemaker activity in colonic ICC.

Objective: To explain process of developing basic veterinary clinical performance guidelines, based on frequently observable clinical manifestations, thereby supporting competencybased veterinary education in Korea. Methods: A structured review of learning outcomes established by Korean Association of Veterinary Medical Colleges (KAVMC) was conducted by a planning committee including veterinary educators, practitioners, and advisory members. Owner-oriented descriptions were used to frame each performance task, and each was mapped to corresponding learning outcomes. These tasks were aligned with learning outcomes recommended by the KAVMC to support the development of communication, clinical reasoning, and performance-related competencies among veterinary students, thereby enhancing day-one clinical readiness. Results: In total, 63 clinical manifestations for a guidebook format that can be used for clinical education were identified and categorized by organ systems that are described in language understandable to animal owners. Conclusions and Relevance: The basic veterinary clinical performance guidelines based on common clinical manifestations would serve as a vital component in veterinary education to reinforce core graduation competencies.

Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Purpose: The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone. Materials and Methods: From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery. Results: There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups. Conclusion Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.