BACKGROUND/OBJECTIVES: The fruit of Cydonia oblonga Miller (COM) is used traditionally in Mediterranean region medicine to prevent or treat obesity, but its mechanism of action is still unclear. Beyond a demonstrated anti-obesity effect, the fruit was tested for the mechanism of adipogenesis in 3T3-L1 preadipocytes.MATERIALS/METHODS: 3T3-L1 preadipocytes were cultured for 8 days with COM fruit extract (COME) at different concentrations (0–600 µg/mL) with adipocyte differentiation medium. The cell viability was measured using an MTT assay; triglyceride (TG) was stained with Oil Red O. The expression levels of the adipogenesis-related genes and protein expression were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: COME inhibited intracellular TG accumulation during adipogenesis. A COME treatment in 3T3-L1 cells induced upregulation of the adenosine monophosphateactivated protein kinase (AMPK)α phosphorylation and downregulation of the adipogenic transcription factors, such as sterol regulatory element-binding protein 1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α. The COME treatment reduced the mRNA expression of fatty acyl synthetase, adenosine triphosphatecitrate lyase, adipocyte protein 2, and lipoprotein lipase. It increased the mRNA expression of hormone-sensitive lipase and carnitine palmitoyltransferase I in 3T3-L1 cells. CONCLUSIONS COME inhibits adipogenesis via the AMPK signaling pathways. COME may be used to prevent and treat obesity.

Purpose: Recent studies have revealed that the expression of cancer-associated fibroblast (CAF) activation biomarkers in cancer cells is associated with clinical outcomes in patients with certain types of malignant tumors. However, whether the expression of CAF activation biomarkers affects the prognosis of colorectal cancer (CRC) has not been fully elucidated. This study aimed to evaluate the association between the expression of CAF activation biomarkers in cancer cells with cancer invasion and long-term oncological outcomes in patients with CRC. Methods: Cancer specimens obtained from 135 patients with stage I–III CRC were examined using immunohistochemical staining to evaluate the expression of fibroblast specific protein-1 (FSP-1), fibroblast activation protein α (FAPα), α-smooth muscle actin (α-SMA), and vimentin in cancer cells. Results: FSP-1 expression in cancer cells was significantly associated with lymphatic invasion, perineural invasion, tumor (T) status, and lymph node (N) status. FAPα expression in cancer cells was significantly associated with lymphatic invasion. On univariate and multivariate analyses, FSP-1 and α-SMA expression in cancer cells were associated with a short 10-year overall survival (OS) and high 10-year systemic recurrence (SR), respectively. Tumor budding was associated with a short 10-year OS. However, FAPα and vimentin did not contribute to the prognosis in this study. Conclusion In this study, we found that FSP-1 expression in cancer cells was related to cancer invasion. Additionally, FSP-1 and α-SMA expression in cancer cells was associated with 10-year OS and SR, respectively. Therefore, these markers may be used as predictors of long-term oncological outcomes in patients with CRC.

Purpose: This prospective, single-center, open-label, therapeutic confirmatory, randomized clinical trial aimed to assess the alleviation of anal pain by applying structured anal skin care including skin protectants in rectal cancer patients with low anterior resection syndrome (LARS) combined with anal pain. Methods: From December 2017 to May 2020, 42 patients with LARS (scores of ≥21) and anal pain (visual analogue scale [VAS] score of ≥3) were randomly assigned and observed for 4 weeks. The conventional treatment consisted of dietary management, sitz baths, prohibition of anal scrubbing, loperamide, and dioctahedral smectite. In the anal care group, cleanser, barrier cream, and barrier spray were applied to the anal skin after defecation following the conventional treatment. The primary outcome was analgesic effect on anal pain after 2 weeks of structured treatment (anal care group) or conventional (control group). The cutoff for analgesic effect was a decrease in the anal pain score (VAS score of ≥2 or ≥30% reduction). Results: As a primary outcome, the analgesic effect was significantly higher in the anal care group (P = 0.034). The incontinence-associated dermatitis skin condition score was significantly improved in the anal care group than control group after 4 weeks (P = 0.023). There were no significant differences in LARS scores and quality of life scores between 2 groups. Conclusion Structured anal skin care has a significant analgesic effect in reducing anal pain and improving anal skin conditions in patients with LARS after rectal cancer surgery.

Objective: Cognitive reserve (CR) protects against cognitive decline by utilizing functional connectivity (FC) in the brain, such as the default mode network (DMN). We studied whether CR in individuals with predementia would correlate with better cognition and increased DMN FC in the resting brain. Methods: Fifty-four participants with subjective cognitive decline or mild cognitive impairment completed the Cognitive Reserve Index (CRI) questionnaire, and underwent a comprehensive neuropsychological test battery and resting state functional magnetic resonance imaging. Correlation and regression analyses for clinical variables and seed-to-voxel analyses of CR-related FC in the DMN were conducted. Results: CRI total (β=0.42, p=0.001), education (β=0.39, p=0.001), and leisure time (β=0.33, p=0.009) predicted the MiniMental State Examination. The CRI education predicted verbal memory recall (β=0.32, p=0.017), confrontational naming (β=0.57, p<0.001), and phonemic fluency (β=0.43, p=0.004). In the DMN in the resting brain, the CRI total correlated with increased FC, based on the posterior cingulate to both lateral parietal cortices. Conclusion In individuals with predementia, comprehensive CR correlated with an enhanced network in the DMN in the resting state. These results may support the neural correlate of CR during the initial stage of cognitive decline.

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

Objective: The emergency medical service (EMS) is expected to improve the prognosis of patients suffering from acutemyocardial infarction (AMI). We investigated the impact of utilizing EMS on the clinical outcomes of AMI patients. Methods: From November 2011 to November 2015, a total of 13,102 patients in the Korea Acute Myocardial InfarctionRegistry-National Institute of Health (KAMIR-NIH) registry were enrolled. Patients were divided into two groups: the EMSgroup, first medical contact (FMC) with 119; the non-EMS group, the FMC at local hospitals that were not available forpercutaneous coronary intervention. The authors analyzed the mortality and major adverse cardiac and cerebrovascularevents during one-year of clinical follow-up. Results: A total of 8,863 patients were finally analyzed for this study, and a total of 1,999 patients (22.6%) utilized theEMS as FMC. The patients utilizing EMS were more frequently diagnosed with ST-segment elevation AMI. At presentation,the EMS group had a higher incidence of Killip class IV, and they had a shorter symptom-to-door time than non-EMS group. The patients utilizing EMS had higher incidence of peri-procedural complications and in-hospital mortality.The multivariate logistic regression analysis with backward elimination revealed that utilizing EMS is an independent factorfor predicting lower one-year mortality. Conclusion This study has demonstrated that the high-risk AMI patients can utilize the EMS in Korea. The EMS grouphas more favorable clinical outcome during one-year follow-up after discharge than the non-EMS group, whereas it had ahigher rate of death during hospitalization compared with that of the non-EMS group.

Purpose: This preliminary in-vitro study was designed to evaluate the risk factors of compression injury from use of a circular stapler for end-to-end anastomosis. Methods: Transparent collagen plates were prepared in dry and wet conditions. Physical properties of collagen plates and porcine colon tissue were examined using a rheometer. Adjustable and fixed-type circular staplers were applied on the collagen plates and the gap distance and compressive pressure were measured during anvil approximation. Tissue injury was evaluated using a compression injury scale. Compression properties were accessed to optimal or overcompression based on gap distance. Results: Unacceptable injuries were rarely observed on the dry collagens, regardless of compression device. In the adjustable compression, the compressibility ratio was similar between dry and wet collagen. Overcompression and unacceptable injury increased on the wet collagens. In the fixed compression, the compressibility ratio increased significantly and unacceptable injuries were observed in more than 50% of wet collagens. Peak pressure was significantly higher in the fixed-compression types than those of adjustable type. On bivariate correlation analysis, fixed-compression type and wet collagens were respectively associated with overcompression. On multivariate analysis, edematous collagen condition was the most important risk factor and proximal anvil side, fixed compression type, and overcompression were also independent risk factors for unacceptable compression injury. Conclusion In the edematous tissue condition, unintentional overcompression could be increased and result in tissue injury on the compression line of the circular stapler.

PURPOSE: We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC). METHODS: Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness. RESULTS: The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding. CONCLUSION: The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.
Collagen ; Colorectal Neoplasms ; Fibroblasts ; Humans ; Islands ; Receptor, Epidermal Growth Factor ; Recurrence ; Wound Healing

PURPOSE: The aim of this study is to evaluate the safety and usefulness of indocyanine green (ICG) angiography in laparoscopic colorectal surgery and to explore its educational benefits in surgical beginners. METHODS: From July to October of 2015, a total of 21 patients with colorectal cancer underwent laparoscopic surgery using the fluorescence-guided imaging system, IMAGE1 S™ (Karl Storz, Germany). Real-time ICG fluorescence images and red inversion images were juxtaposed with standard white-light images for assessment of colonic perfusion. A surgical beginner group comprised of medical students (n=11) and surgical residents (n=11) were then questioned postoperatively about the colonic transection line and mesenteric vascular integrity across various image modes to determine the most proper view for surgical decision. RESULTS: A total of 21 patients underwent laparoscopic colorectal surgery using ICG angiography. Mean patient age was 69.7 years (52~77 years). Mean time-to-detection for the marginal arteries and colonic wall were 26.7 (range, 4~45) and 47.3 (range, 20~77) seconds, respectively. No injection-related adverse events were observed. Rate of change in the colonic transection line across modes was 59.9% (33.3~66.7%) in the surgical beginners. Decisions made by surgical beginners on the transection line were varied with the standard image, but converged to 81.8% in the ICG with red inversion mode. Surgical beginners preferred ICG with red inversion mode for assessment of mesenteric vascular integrity. CONCLUSION: ICG angiography seems to be safe and useful in evaluating colonic perfusion for transection decisions and could have educational benefits for surgical beginners in training to make surgical decisions.
Angiography* ; Arteries ; Colon ; Colorectal Neoplasms ; Colorectal Surgery* ; Fluorescence ; Humans ; Indocyanine Green* ; Laparoscopy ; Perfusion ; Students, Medical

PURPOSE: This study aimed to identify the best way of developing equivalent item sets and to propose a stable and effective management plan for periodical licensing examinations. METHODS: Five pre-equated item sets were developed based on the predicted correct answer rate of each item using linear programming. These pre-equated item sets were compared to the ones that were developed with a random item selection method based on the actual correct answer rate (ACAR) and difficulty from item response theory (IRT). The results with and without common items were also compared in the same way. ACAR and the IRT difficulty were used to determine whether there was a significant difference between the pre-equating conditions. RESULTS: There was a statistically significant difference in IRT difficulty among the results from different pre-equated conditions. The predicted correct answer rate was divided using 2 or 3 difficulty categories, and the ACAR and IRT difficulty parameters of the 5 item sets were equally constructed. Comparing the item set conditions with and without common items, including common items did not make a significant contribution to the equating of the 5 item sets. CONCLUSION: This study suggested that the linear programming method is applicable to construct equated-item sets that reflect each content area. The suggested best method to construct equated item sets is to divide the predicted correct answer rate using 2 or 3 difficulty categories, regardless of common items. If pre-equated item sets are required to construct a test based on the actual data, several methods should be considered by simulation studies to determine which is optimal before administering a real test.
Licensure ; Methods ; Programming, Linear