Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Epidemiologic trends of patients who visited nationwide emergency departments: a report from the National Emergency Department Information System (NEDIS) of Korea, 2018-2022.

OBJECTIVE: : This study analyzed trends in emergency department (ED) visits in South Korea using the National Emergency Department Information System (NEDIS) data from 2018 to 2022. METHODS: : This was a retrospective observational study using data from the NEDIS database from 2018 to 2022. Age- and sex-standardized ED visits per 100,000 population, as well as age- and sex-standardized rates for mortality, admission, and transfer, were calculated. RESULTS: : The standardized ED visits per 100,000 population was approximately 20,000 from 2018 to 2019 and decreased to about 18,000 in 2022. The standardized mortality rate ranged from 1.4% to 1.7%. The admission rate (18.4%-19.4%) and the transfer rates (1.6%-1.8%) were similar during the study period. Approximately 5.5% of patients were triaged as Korean Triage and Acuity Scale score 1 or 2. About 91% of patients visited the ED directly and 21.7% of patients visited the ED with an ambulance. The ED length of stay was less than 6 hours in 90.3% of patients and the ED mortality rate was 0.6%. Acute gastroenteritis was the most common diagnosis. Respiratory virus symptoms, such as fever and sore throat, were also common chief complaints. CONCLUSION: : ED visits decreased during the 5-year period, while admission, transfer, and death rates remained relatively stable.

Characteristics of pediatric emergency department visits before and during the COVID-19 pandemic: a report from the National Emergency Department Information System (NEDIS) of Korea, 2018-2022.

OBJECTIVE: : As of 2018, approximately 1.2 million pediatric patients visited emergency departments (EDs) in Korea, showing a steady increase. Given the distinct differences between children and adults, it is vital to examine the epidemiological characteristics of pediatric patients visiting the ED. METHODS: : This study retrospectively analyzed the ED use patterns of pediatric patients <18 years old in Korea from January 1, 2018, to December 31, 2022, using data from the National Emergency Department Information System (NEDIS). RESULTS: : Most pediatric ED patients were boys, with an average age of 6.6±5.3 years. Patients younger than 1 year and those in critical condition had longer ED stays and more frequently required hospital admission and used the 119-ambulance service. The primary symptom was fever, and the most common discharge diagnosis was gastroenteritis. Following the declaration of the COVID-19 pandemic in 2020, ED visits decreased by 49%. Meanwhile, there was an increase in in-hospital mortality rate/age- and sex-standardized mortality rate per 100,000 ED visits, Admission and transfer rates remained similar between before and after the start of the pandemic. CONCLUSION: : Through this analysis, we identified the characteristics of pediatric patients visiting EDs in Korea. We observed a sharp decline in ED visits after the start of the COVID-19 pandemic. From there, ED visits slowly increased but remained below prepandemic levels for 3 years. This research will serve as a foundational resource for appropriately allocating and preparing pediatric ED resources.

Emergency department utilization in elderly patients: a report from the National Emergency Department Information System (NEDIS) of Korea, 2018-2022.

OBJECTIVE: : With general aging of the population, emergency department (ED) utilization by elderly patients is increasing. In this study, we analyzed data on ED visits of patients aged 65 years and older in Korea. METHODS: : The study is a retrospective analysis of National Emergency Department Information System (NEDIS) data from 2018-2022, focusing on patients aged 65 years and older who visited EDs across Korea. ED utilization data were analyzed using Korean Triage and Acuity Scale (KTAS) scores. The patients were divided into three age groups, and common chief complaints and diagnoses were identified. Age- and sex-standardized ED visits per 100,000 population and outcomes were also analyzed. RESULTS: : During the study period, there was a total of 9,803,065 elderly patient ED visits. The mean patient age was 76.4±7.6 years, and 47.6% were men. The ED mortality rate and in-hospital mortality rate were 1.8% and 4.6%, respectively. The KTAS scores 1-2 group accounted for 11.0% of patients, KTAS score 3 group for 42.5%, KTAS scores 4-5 group for 37.2%, and KTAS score unknown group for 9.4%. When patients were categorized into three age groups, the oldest group exhibited the highest rates of KTAS score 1, severe illness diagnoses, and mortality. The most frequently reported chief complaint was abdominal pain, and the most common diagnosis was light headedness. When analyzing the data by year, the COVID-19 outbreak had a discernible impact on ED visits and clinical outcomes. CONCLUSION: : Over the past 5 years, ED visits for elderly patients have averaged 26,050 per 100,000 population per year, with a temporary decline during the COVID-19 pandemic and a subsequent upward trend.

Effectiveness and Safety of Endoscopic Submucosal Dissection for Colorectal Neoplasm in Patients with High Charlson Comorbidity Index Score: A HASID Multicenter Study.

Endoscopic submucosal dissection (ESD) is an effective method for removing early colorectal lesions. However, research on the safety and efficacy of ESD in patients with various underlying conditions remains limited. This study retrospectively examined ESD outcomes in colorectal neoplasm patients from five tertiary medical centers. The Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) were analyzed, and the differences in complete resection and complication rates were analyzed. The CCI, ACCI, and complication rates tended to gradually increase proportionally, and the complication resection rate increased from CCI 2 to ACCI 4 as the starting point, followed by a decreasing trend. Of these, 140 patients (9.7%) had a CCI score of 3 or higher. The high CCI group was older (70.6% vs. 64.7%, p < 0.01) and had a higher proportion of men (70.7% vs. 58.7%, p < 0.01) than the low CCI group. The high CCI group had a higher incidence of cancer than the low CCI group (77.9% vs. 65.2%, p < 0.01). The en bloc resection rate (90.0% vs. 89.3%, p = 0.79) and complete resection rate (75.7% vs. 81.2%, p = 0.12) were not significantly different between the two groups. Colorectal ESD can be safely and effectively performed in patients with various underlying medical conditions.

Modified underwater endoscopic mucosal resection for intermediate-sized sessile colorectal polyps.

Introduction: Underwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions. Methods: This prospective, observational, single-center study included consecutive patients with intermediate-sized (10-20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications. Results: Forty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42-607) and 50 mL (30-130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized <15 mm (p < 0.01). Muscle entrapment was found in 71.4% of patients with polyps sized ≥15 mm and 10% <15 mm (p < 0.01). Immediate bleeding occurred in 12.8% of cases and was controlled using a snare tip or hemostatic forceps. Snare-tip ablation and hemostatic forceps ablation were performed in 27.7 and 6.4% of patients, respectively. No delayed bleeding, perforation, or any other complications were reported. Conclusion: Modified UEMR can be used in cases in which securing visibility or performing the existing UEMR is challenging. Careful treatment is required when removing polyps >15 mm in size.

2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

Trends in emergency department visits for suicide attempts before and during the COVID-19 pandemic in Korea: A nationwide study, 2016-2021.

BACKGROUND: There is increasing concern that the effects of the COVID-19 pandemic will result in excess suicides by increasing known risk factors, such as suicide attempts. However, evidence on the long-term impacts of COVID-19 on suicide attempts is lacking. We aimed to assess the short- and long-term effects of the COVID-19 pandemic on patients with suicide attempts in emergency departments (EDs) and to evaluate age- and sex-specific differences. METHOD: We conducted nationwide cross-sectional study among patients with suicide attempts in the ED from 2016 to 2021. The trend test were used to determine whether study subjects were affected by changes in ED visits for suicide attempts. We estimated the average annual percentage change (APC) stratified by sex and age groups. RESULTS: The number of ED visits related to suicide attempts increased from 27,581 in 2016 to 37,719 in 2021. In particular, it decreased immediately after the COVID-19 pandemic but increased again in 2021. We identified that the average APC increased by 6.8 % overall, 1.6 % among males, and 10.8 % among females. Moreover, the APC of trend sharply increased in patients aged 10s and 20s. The in-hospital mortality was 3.6 % for females, compared to 9.5 % for males, which showed sex differences. LIMITATIONS: This study was limited to confirming causal relationship based on a descriptive study. CONCLUSIONS: The incidence of suicide attempts in ED has increased in Korea. In particular, there was a sharp increase among women, adolescents and young adults. Patient-tailored treatment and preventive medical system for suicide attempts is important.

Comparison of optimal bowel cleansing effects of 1L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate: A randomized controlled study.

Various low-volume bowel cleansing formulations that improve compliance have been approved and are being used in clinical practice. This study aimed to compare the effectiveness of 1 L polyethylene glycol (PEG) with ascorbic acid with that of sodium picosulfate (PICO) with magnesium citrate. This was a multicenter, randomized controlled, non-inferiority study. Patients were randomized into a 1 L PEG with ascorbic acid group and a PICO with magnesium citrate group according to the bowel cleansing agent used. Colonoscopy was performed as a single-blind study wherein the endoscopist had no information about any bowel preparation agent. The efficacy of bowel cleansing was assessed using the Harefield Cleansing Scale (HCS), and adverse events, preferences, and satisfaction were evaluated using a patient-reported questionnaire before colonoscopy. A total of 254 participants were randomly assigned to two groups: 115 in the 1 L PEG with ascorbic acid group and 113 in the PICO with magnesium citrate group. Overall bowel cleansing success was not statistically different between the two groups (97.4 vs. 97.3%), confirming that 1 L PEG with ascorbic acid was not inferior to PICO with magnesium citrate (lower confidence limit, -4.15%; p = 1.00). High-quality bowel cleansing was achieved in 87% of the 1 L PEG with ascorbic acid group and 77% of the PICO with magnesium citrate group (Lower confidence limit, 1.29%, p = 0.05). In terms of patient satisfaction, PICO with magnesium citrate was better, but compliance and side effects were similar in both groups. The 1 L PEG with ascorbic acid showed similar efficacy and adverse events as PICO with magnesium citrate. Although 1 L PEG with ascorbic acid is very effective in bowel preparation despite its small volume, it is necessary to increase satisfaction such as taste and feeling.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

Early gastric neoplasms are significant risk factor for colorectal adenoma: A prospective case-control study.

Although gastric cancer patients have a high incidence and risk of colorectal cancer, evidence is lacking regarding whether early gastric neoplasms (EGNs), such as gastric adenomas and early gastric cancer, are risk factors for colorectal adenoma. This study aimed to investigate the incidence of colorectal adenomas in patients with EGN. This prospective study was conducted between January 2015 and December 2016. Of the 307 patients who underwent gastric endoscopic submucosal dissection for EGN, 110 patients were enrolled in the EGN group, and 110 age- and sex-matched healthy persons from the screening population were included in the control group in a 1:1 ratio. Demographic factors and results of colonoscopy, including quality assessment, were collected, and analyzed. No significant differences in the quality of colonoscopy, including bowel preparation, cecal intubation rate, and withdrawal time between the 2 groups, were observed. The incidence of colorectal adenoma was significantly higher in the EGN group than in the control group (55.5% vs 26.4%, P = .001). Multivariate analysis confirmed that old age (odds ratio: 1.04, 95% confidence interval: 1.01-1.08, P = .005) and a history of EGN (odds ratio: 4.99, 95% confidence interval: 2.60-9.57, P = .001) were independent risk factors for colorectal adenoma. This is the first prospective study to reflect the quality indicator of colonoscopy and confirmed that old age and a history of EGN are significant risk factors for colorectal adenomas. Therefore, more stringent colonoscopy surveillance should be considered in elderly patients with EGN.

ω-3 fatty acid-enriched parenteral nutrition shortens hospital stay in acute variceal bleeding cirrhotic patients.

ABSTRACT: Acute variceal bleeding, a crucial complication of liver cirrhosis requires high energy expenditures but gastrointestinal bleeding limits enteral feeding in the acute stage. We investigated the safety and efficacy of ω-3 fatty acid-enriched parenteral nutrition in acute variceal bleeding patients.In this retrospective study, a total of 208 cirrhotic patients with acute variceal bleeding who underwent parenteral nutrition in the absence of enteral nutrition were enrolled. Among the patients, 86 patients received ω-3 fatty-acid-enriched parenteral nutrition. The primary endpoint was to evaluate the duration of hospital stay and the presence of clinical complications of liver cirrhosis.The mean age of the patients enrolled was 54.9 years-old and 185 patients (88.9%) were male. The cause of liver cirrhosis, Child-Pugh score and comorbidities were statistically not different. Patients with ω-3 enriched parenteral nutrition had a significantly lower systolic blood pressure and total bilirubin levels. The difference in the in-hospital mortality (P = .813) or rate of complications (P = .880) was not statistically significant. The duration of hospital stay was significantly shorter in the patients who underwent ω-3 fatty acid-enriched parenteral nutrition (10.7 ±â€Š7.3 vs 7.9 ±â€Š4.2 days, P = .001).In liver cirrhosis patients with acute variceal bleeding, ω-3 fatty acid-enriched parenteral nutrition significantly decreased the length of hospital stay. Further prospective studies to consolidate these findings are warranted.

Efficacy of sigmoidoscopy for evaluating disease activity in patients with ulcerative colitis.

BACKGROUND: Endoscopic assessment of disease activity is a key parameter in the management of ulcerative colitis. Whether sigmoidoscopy alone is sufficient to evaluate the disease activity in ulcerative colitis lacks studies. METHODS: We retrospectively analyzed the medical records and endoscopic results of patients with ulcerative colitis followed by colonoscopy in seven tertiary hospitals between January 2012 and December 2018. Endoscopic disease activity was scored using the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for each segment from the colonoscopy images. Concordance was evaluated by comparing the highest MES and UCEIS in the rectosigmoid and proximal regions to confirm the usefulness of sigmoidoscopy. RESULTS: A total of 500 colonoscopic examinations from 333 patients were enrolled. Only in 7.6% [k(kappa): 0.893, r(Spearman): 0.906, p < 0.001] and 8.6% [k(kappa): 0.890, r(Spearman): 0.914; p < 0.001] of cases, MES and UCEIS scored more severely in the proximal colon. Comparison of active disease (MES ≥ 2) in the rectosigmoid area and the entire colon showed a high concordance rate [k(kappa): 0.899, r(Spearman): 0.904, p < 0.001]. Endoscopic healing (MES = 0) also showed a high concordance rate [k(kappa): 0.882, r(Spearman): 0.887, p < 0.001]. In 38 cases (7.6%) of patients with a higher MES in the proximal area, it was significantly higher in patients with previous extensive colitis. CONCLUSIONS: Sigmoidoscopy and colonoscopy showed a high concordance rate. Therefore, sigmoidoscopy is considered a sufficient substitute for colonoscopy. However, colonoscopy should be considered in patients with previous extensive colitis.

Prognosis and risk factors of electrocoagulation syndrome after endoscopic submucosal dissection in the colon and rectum. Large cohort study.

BACKGROUND: There are few studies on electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD). This study aimed to investigate the various risk factors associated with thermal injury and to determine the prognosis of post-colorectal ESD electrocoagulation syndrome (PECS). METHODS: We conducted a retrospective analysis of the medical records of 395 colorectal neoplasms of 508 patients who were treated with colorectal ESD between January 2013 and December 2019. The incidence, risk factors, and clinical outcomes of colorectal PECS were evaluated and analyzed. RESULTS: Colorectal PECS occurred in 25 patients (6.3%). The PECS group had a larger lesion size (≥ 40 mm), lesions with fibrosis, longer procedure time, older age, and a larger amount of submucosal injection per square meter than the non-PECS group. In multivariate analysis, lesion with size ≥ 40 mm (odds ratio [OR] 16.941, 95% confidence interval [CI] 3.869-74.178), lesions with fibrosis (OR 7.127, 95% CI 2.541-19.984), old age (OR 1.068, 95% CI 1.010-1.130), and amount of submucosal injection per square meter (OR 1.067, 95% CI 1.015-1.121) were independent risk factors. The PECS group had more fasting days (3.08 vs 1.56 days, P < 0.001), longer hospital stays (7.04 vs 4.09 days, P < 0.001), and higher medical costs (2367 vs 2046, US$, P = 0.004) than the non-PECS group. CONCLUSION: Lesions with size ≥ 40 mm, lesions with fibrosis, old age, and amount of submucosal injection per square meter were independent risk factors. Therefore, caution should be exercised when performing colorectal ESD in patients with these risk factors.

Case report of gastric syphilis in Korea: Clinical features, pathology, management, and prognosis.

RATIONALE: Syphilis is a contagious infectious disease caused by Treponema pallidum. Gastric involvement of syphilis is rare and has nonspecific gastrointestinal symptoms and endoscopic findings. To date, 16 cases have been reported in Korea. Here, we report 2 additional cases of gastric syphilis in men in their 30 second. PATIENTS CONCERNS: Two 35- and 33-year-old men presented with epigastric pain. DIAGNOSIS: The serum venereal disease research laboratory and fluorescent treponemal antibody absorption tests were positive. Esophagogastroduodenoscopy showed multiple variable-sized flat elevated lesions and geographic ulcers with whitish exudates in the antrum and body. Warthin-Starry silver staining of endoscopic biopsy specimens confirmed gastric syphilis. INTERVENTIONS: The patients were treated with an intramuscular injection of 2.4 million units of benzathine penicillin once a week for 3 weeks. OUTCOMES: Clinical symptoms and gastric lesions were completely resolved. LESSONS: First, gastric syphilis, despite its rarity and nonspecific symptoms and endoscopic findings, should be considered in a rare extracutaneous presentation of syphilis. Second, a high index of clinical suspicion and an accurate diagnosis based on a combination of clinical, radiological, endoscopic, serologic, and histopathologic findings provide an opportunity to identify and treat patients with gastric syphilis.

Characterization of subcellular localization of eukaryotic clamp loader/unloader and its regulatory mechanism.

Proliferating cell nuclear antigen (PCNA) plays a critical role as a processivity clamp for eukaryotic DNA polymerases and a binding platform for many DNA replication and repair proteins. The enzymatic activities of PCNA loading and unloading have been studied extensively in vitro. However, the subcellular locations of PCNA loaders, replication complex C (RFC) and CTF18-RFC-like-complex (RLC), and PCNA unloader ATAD5-RLC remain elusive, and the role of their subunits RFC2-5 is unknown. Here we used protein fractionation to determine the subcellular localization of RFC and RLCs and affinity purification to find molecular requirements for the newly defined location. All RFC/RLC proteins were detected in the nuclease-resistant pellet fraction. RFC1 and ATAD5 were not detected in the non-ionic detergent-soluble and nuclease-susceptible chromatin fractions, independent of cell cycle or exogenous DNA damage. We found that small RFC proteins contribute to maintaining protein levels of the RFC/RLCs. RFC1, ATAD5, and RFC4 co-immunoprecipitated with lamina-associated polypeptide 2 (LAP2) α which regulates intranuclear lamin A/C. LAP2α knockout consistently reduced detection of RFC/RLCs in the pellet fraction, while marginally affecting total protein levels. Our findings strongly suggest that PCNA-mediated DNA transaction occurs through regulatory machinery associated with nuclear structures, such as the nuclear matrix.

Isolation of Polysaccharides from Trichoderma harzianum with Antioxidant, Anticancer, and Enzyme Inhibition Properties.

In this work, a total of six polysaccharides were isolated from culture filtrate (EPS1, EPS2) and mycelia (IPS1-IPS4) of Trichoderma harzianum. The HPLC analysis results showed that EPS1, EPS2, IPS1, and IPS2 were composed of mannose, ribose, glucose, galactose, and arabinose. The FT-IR, 1H, and 13C NMR chemical shifts confirmed that the signals in EPS1 mainly consist of (1→4)-linked α-d-glucopyranose. EPS1 and IPS1 showed a smooth and clean surface, while EPS2, IPS2, and IPS3 exhibited a microporous structure. Among polysaccharides, EPS1 displayed higher ABTS+ (47.09 ± 2.25% and DPPH (26.44 ± 0.12%) scavenging activities, as well as higher α-amylase (69.30 ± 1.28%) and α-glucosidase (68.22 ± 0.64%) inhibition activity than the other polysaccharides. EPS1 exhibited high cytotoxicity to MDA-MB293 cells, with an IC50 of 0.437 mg/mL, and this was also confirmed by cell staining and FACS assays. These results report the physicochemical and bioactive properties of polysaccharides from T. harzianum.

Jagged-1 Expression Level Is Correlated With Recurrence of Stage III Colorectal Cancer in Patients Receiving Adjuvant Chemotherapy.

BACKGROUND/AIM: Previous reports have indicated that increased expression of Jagged-1 (JAG1) may predict chemotherapy response and poor prognosis for patients with recurrent or metastatic colorectal cancer (CRC). This study aimed to investigate the clinical impact of JAG1 expression level in patients with CRC, including recurrence, especially in those diagnosed with lymph node-positive stage III CRC who underwent complete resection and appropriate adjuvant chemotherapy. PATIENTS AND METHODS: All patients were enrolled through a retrospective chart review, and only those for whom the clinical course and all clinical information were adequately determined according to the inclusion criteria were selected for retrospective review through medical records. Immunohistochemical staining of JAG1 was performed using paraffin-embedded tissue. JAG1 expression was determined by scoring for staining intensity and percentage of positively stained cells; the final JAG1 score was determined as the sum of both scores. RESULTS: Sixteen patients who experienced relapse and 15 without (for over 3 years) were selected. The protein expression level of JAG1 showed a tendency for being lower in the group without recurrence, although not statistically significantly (p=0.083); however, the mean JAG1 expression score was significantly lower in the group without recurrence (1.53 vs. 3.19; p=0.004). The patients were divided into two groups with low and high JAG1 expression. The results showed that high JAG1 expression was significantly associated with recurrence of stage III CRC (p=0.029). CONCLUSION: The expression of JAG1 may be a potential novel biomarker for predicting CRC recurrence.

Location-Based Resource Allocation in Ultra-Dense Network with Clustering.

With the rapid deployment of present-day mobile communication systems, user traffic requirements have increased tremendously. An ultra-dense network is a configuration in which the density of small base stations is greater than or equal to that of the user equipment. Ultra-dense networks are considered as the key technology for 5th generation networks as they can improve the link quality and increase the system capacity. However, in an ultra-dense network, small base stations are densely positioned, so one user equipment may receive signals from two or more small base stations. This may cause a severe inter-cell interference problem. In this study, we considered a coordinated multi-point scenario, a cooperative technology between base stations to alleviate the interference. In addition, to suppress the occurrence of severe interference at the cell edges, link formation was carried out by considering the degree of cell load for each cluster. After the formation of links between all the base stations and user equipment, a subcarrier allocation procedure was performed. The subcarrier allocation method used in this study was based on the location of base stations with clustering to improve the data rate and reduce the interference between the clusters. Power allocation was based on the channel gain between the base station and user equipment. Simulation results showed that the proposed scheme delivered a higher sum rate than the other resource allocation methods reported previously for various types of user equipment.