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: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Purpose: Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC. Materials and Methods: We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group. Results: Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model. Conclusions The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.

Background: Despite the critical role of vitamin D in various biological processes, its impact on frailty—a condition closely linked to biological age—remains inconclusive. This study aimed to explore the association between serum 25-hydroxyvitamin D (25[OH] D) levels and frailty status in older Korean adults, utilizing a comprehensive frailty index (FI) and a nationally representative dataset. Methods: This cross-sectional study included 6,589 participants aged ≥65 years from the Korea National Health and Nutrition Examination Survey (2008–2012). Frailty was assessed using a deficit accumulation FI based on 38 physical, cognitive, psychological, and social items. Results: After adjusting for potential confounders, frail men showed 6.8% lower serum 25(OH)D concentrations compared to nonfrail controls (P=0.007). Men in the lowest serum 25(OH)D quartile (≤39.3 nmol/L) exhibited a 5.3% higher FI (P=0.047) and 1.71-fold increased odds of frailty (P=0.005), compared to those in the highest quartile (>63.3 nmol/L). Similarly, men with vitamin D deficiency (<30 nmol/L) exhibited a 9.6% higher FI compared to those with sufficient vitamin D levels (≥50 nmol/L; P=0.004). However, no significant association between serum 25(OH)D concentration and frailty was observed in women across any analysis. Conclusion These findings suggest that low serum 25(OH)D concentrations are a potential risk factor for frailty, particularly in men. Further research is warranted to determine whether vitamin D supplementation in such high-risk older adults could help mitigate frailty.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone–tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-b-only, CTGF-only, and TGF-b + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-band CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

Purpose: This study examined the structural and mechanical stability as well as the clinical significance of various fixation constructs for distal tibial fractures using finite element analysis. Materials and Methods: Fracture models with 20 mm and 120 mm defects were produced, and implants of an intramedullary nail and anatomical plate model were applied. An axial load of 800 N with 60% distribution in the medial compartment and 40% in the lateral compartment was applied and analyzed using Ansys ® software. Results: In the intramedullary nail model, the maximum von Mises stress occurred at the primary lag screw hole and adjacent medial cortex, while in the plate model, it occurred at the locking holes around the fracture. The maximum shear stress on the bone and metal implant in the fracture model with a 20 mm defect was highest in the plate assembly model, and in the fracture model with a 120 mm defect, it was highest in the two-lag screw assembly model. Conclusion Based on an analysis of the maximum shear stress distribution, securing the fixation strength of the primary lag screw hole is crucial, and the assembly model of the intramedullary nail with two lag screws and a blocking screw applied was the model that best withstood the optimal load. Securing the locking hole directly above the fracture is believed to provide the maximum fixation strength because the maximum pressure in the plate model is concentrated in the proximal locking hole and the surrounding cortex.

Objective: Emergency department (ED) overcrowding is a global issue that negatively impacts the clinical outcome. Through the coronavirus disease 2019 (COVID-19) pandemic era, overcrowding of ED isolated territory (isolation bed) was aggravated. This study analyzed overcrowding indices of ED isolation beds during the COVID-19 pandemic. Methods: This study was a single-center, retrospective, observational study. The study analyzed 34,925 patients who visited the ED during the COVID-19 pandemic from April 2021 to August 2022. Patients who were treated in isolation beds and regular beds were compared. Among the patients using isolation beds, patients who stayed longer than 720 minutes were also classified and analyzed. Results: During the analysis period, 4,479 and 34,943 patients were treated in the ED isolation bed and ED regular bed, respectively. The overcrowding indices (general ward admission rate, intensive care unit admission rate, ED-length of stay, transfer rate, mortality rate, prolonged ED stay patient ratio) of the isolation beds were significantly higher than those of the ED regular bed (P<0.05). The prolonged ED stay-patient ratio of isolation beds and regular beds was affected by the number of COVID-19 patients (regular bed, r=0.617 and P=0.01; isolation bed, r=0.525 and P=0.03). The average ED-length of stay of isolation beds was longer than that of the ED regular beds. One hundred and forty-five patients were classified as prolonged ED stay patients. Their time from the decision point to the discharge point comprised a higher rate with an average of 76.52%. Conclusion ED isolation beds are more vulnerable to infectious disease outbreaks. A proper medical policy and arrangement management system that can flexibly deal with disaster emergencies are required

Bovine borreliosis, caused by Borrelia theileri which is transmitted via hard tick bites, is associated with mild clinical symptoms, such as fever, lethargy, hemoglobinuria, anorexia, and anemia. Borrelia theileri infects various animals, such as cattle, deer, horses, goats, sheep, and wild ruminants, in Africa, Australia, and South America. Notably, no case of B. theileri infection has been reported in Korean cattle to date. In this study, 101 blood samples were collected from a Korean indigenous cattle breed, among which 1.98% tested positive for B. theileri via nested PCR. The obtained sequences exhibited high homology with B. theileri strains identified in other regions. Phylogenetic analysis of 16S rRNA confirmed the B. theileri group affiliation; however, flagellin B sequences exhibited divergence, potentially due to regional evolutionary differences. This study provides the first molecular confirmation of B. theileri infection in Korean livestock. Further isolation and nucleotide sequence analyses are necessary to better understand the presence of B. theileri strains in cows in Korea.

The prevalence of thyroid cancer in pregnant women is unknown; however, given that thyroid cancer commonly develops in women, especially young women of childbearing age, new cases are often diagnosed during pregnancy. This recommendation summarizes the follow-up and treatment when thyroid cancer is diagnosed during pregnancy and when a woman with thyroid cancer becomes pregnant. If diagnosed in the first trimester, surgery should be postponed until after delivery, and the patient should be monitored with ultrasound. If follow-up before 24–26 weeks of gestation shows that thyroid cancer has progressed, surgery should be considered. If it has not progressed at 24–26 weeks of gestation or if papillary thyroid cancer is diagnosed after 20 weeks of pregnancy, surgery should be considered after delivery.

Surgical resection is typically the primary treatment for differentiated thyroid cancer (DTC), followed by radioactive iodine (RAI) and thyroid-stimulating hormone suppression therapies based on the cancer stage and risk of recurrence. Nevertheless, further treatment may be necessary for patients exhibiting persistent disease following RAI therapy, residual disease refractory to RAI, or unresectable locoregional lesions. This guideline discusses the role of external beam radiotherapy and chemotherapy following surgical resection in patients with DTC. External beam radiotherapy is ineffective if DTC has been entirely excised (Grade 2). Adjuvant external beam radiotherapy may be optionally performed in patients with incomplete surgical resection or frequently recurrent disease (Grade 2). In patients at high risk of recurrence following surgery and RAI therapy, adjuvant external beam radiotherapy may be optionally considered (Grade 3). However, external beam radiotherapy may increase the risk of serious adverse events after tyrosine kinase inhibitor therapy. Therefore, careful consideration is needed when prescribing external beam radiotherapy for patients planning to undergo tyrosine kinase inhibitor therapy. There is no evidence supporting the benefits of the routine use of adjuvant chemotherapy for DTC treatment (Grade 2).