Alzheimer’s disease (AD) is increasingly recognized as a disorder with significant vascular involvement, with microvascular damage and thromboinflammation often preceding classical amyloid pathology by several years. Elevated levels of prothrombin and thrombin, along with aberrant platelet activation, have been reported in individuals with AD. We hypothesized that platelet hyperactivity in AD results from an exaggerated response to thrombin in the presence of elevated amyloid beta 1-40 (Aβ₁₋₄₀), a peptide that accumulates during the early stages of AD. Platelet activation in response to Aβ₁₋₄₀ and thrombin was assessed using aggregation assays with an aggregometer, adhesion measurements by confocal microscopy, and spreading via both confocal microscopy and scanning electron microscopy. Reactive oxygen species (ROS) production and integrin α IIbβ 3 activation were quantified by flow cytometry. The roles of NADPH oxidase (NOX), ROS, and integrin signaling were examined using selective inhibitors. Aβ₁₋₄₀ significantly enhanced thrombin-induced platelet adhesion, aggregation, and spreading via NOX-derived ROS and integrin α IIbβ 3 activation. Aβ₁₋₄₀ also promoted platelet binding to fibrinogen and cerebrovascular endothelial cells, accompanied by distinct morphological changes. Inhibition of NOX or integrin α IIbβ 3 significantly reduced these effects. These findings identify a novel Aβ₁₋₄₀–NOX–ROS–integrin α IIbβ 3 axis that drives platelet hyperactivation and cerebrovascular interactions in AD.Targeting this pathway with antithrombotic or antioxidative strategies may offer therapeutic potential in mitigating AD-associated vascular pathology.

Induced pluripotent stem cells (iPSCs) are a promising cell source for regenerative medicine. Clinical applications require a large number of functional red blood cells (RBCs), making it essential to ensure the proliferation of actively dividing, nucleated erythroblasts derived from iPSCs. Small molecules can enhance the efficiency and frequency of iPSC-derived cell differentiation. Sirtuin 1, a key enzyme in multiple biological processes, has been implicated in enhancing iPSC-derived cell differentiation. However, the specific effects of Sirtuin 1 on erythroblast proliferation from iPSCs remain unclear. Here, we developed a protocol to examine the effects of Sirtuin 1 on erythroblasts after endothelial-to-hematopoietic transition (EHT). We found that Sirtuin 1 activation increased the frequency of CD71＋CD235a＋erythroblasts at the early stage after EHT, suggesting a role for Sirtuin 1 in the proliferation of these specified erythroblasts. These findings reveal that Sirtuin 1 activation benefits erythroblast proliferation and could be considered for translational application in large-scale RBC culture.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Purpose: The management of bowel bladder disorder (BBD) has only been indicated for subjective constipation without objective evidence. We attempted to highlight the radiological findings in patients with BBD and construct a scoring system to identify patients with BBD prior to treatment. Materials and Methods: Forty-five patients with lower urinary tract dysfunction (LUTD) received polyethylene glycol for 2 months before bladder medication for LUTD. Based on partial response to LUTD following treatment, we divided the patients into LUTD-fecal impaction (FI) and LUTD not attributed to FI (LUTD-NFI) groups. Pre/post-treatment kidney, ureter, and bladder (KUB) were compared with respect to several radiographic parameters. Items with significant changes after treatment were included in the scoring system. The accuracy and inter-rater agreement were also evaluated. Results: Cecal dilation, descending colon dilation, fecal quality, and overall haziness were found to undergo significant changes after laxative treatment. We assigned 0 to 2 points for each item, with a total score of 8. Receiver operating characteristic curve analysis revealed a cutoff value of 5 between LUTD-FI and LUTD-NFI, with 79% sensitivity and 88% specificity. The scoring system was instructed to six doctors who were unaware of it and was then tested on previous patients, which showed a substantial concordance rate (κ=0.79, p<0.05). Conclusions Fecal scoring system based on KUB was beneficial in identifying children with LUTD attributed to FI. This may provide an opportunity to obtain objective FI data as an alternative to subjective assessment of constipation.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

A common goal in reconstructing the umbilicus is to achieve an aesthetically pleasing result. This single-subject study demonstrates the outcome of managing an umbilical keloid scar using a single excisional line. A patient presented with a large, oval keloid scar at the center of his abdomen. The scar, measuring 4×3 cm in diameter, was deformed to the extent that it completely obscured the umbilicus. The patient frequently experienced intermittent inflammation at the site of the scar. We planned a triangular incision around the keloid. The umbilical keloid was excised and reconstructed using a flap anchored along the lower edge of the triangle. The triangular flap was elevated and the deep dermis of its cephalic portion was attached to the linea alba. The remainder of the flap was sutured at the center to create a conical shape. Eleven months post-procedure, the umbilicus maintained an aesthetically pleasing appearance with proper depth, superior hooding, and a concave shape without protrusion. An advantage of this straightforward surgical method is that it allows for simultaneous resection and reconstruction without the need for additional flap design. This method is expected to be a useful option for reconstructing umbilical keloids the size of a fully developed umbilicus.

The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Purpose: Firefighting duties range from field roles such as suppression, rescue, and emergency medical services (EMS) to various administrative tasks. Despite these differences, they face uniform fitness standards in Korea. This study seeks to define distinct fitness needs for each duty and provide data for customized standards. Methods: One hundred seventy-six Korean male firefighters participated, categorized into suppression (n=76), rescue (n=22), administrative (n=27), and EMS (n=51) roles. All underwent maximal oxygen consumption (VO2 max) tests for aerobic capacity, with body composition measured using bioelectrical impedance and height recorded with a stadiometer. Results: The VO2 max (mL/kg/min) among Korean male firefighters varied across different job duties: suppression (39.96±5.84), rescue (44.84±4.85), administration (40.27±7.01), and EMS (40.51±6.75). Rescue had the highest VO2 max, which was significantly higher (p=0.013). The body mass index (BMI, kg/m2 ) values were as follows: suppression (25.07±2.55), rescue (24.95±1.71), EMS (24.33±3.21), and administration (25.10±2.48). There was no statistically significant difference in BMI values (p=0.464). Conclusion This study evaluated the VO2 max and BMI of South Korean male firefighters according to their job duties. It found that 54.5% did not meet the recommended VO2 max standard of 42 mL/kg/min for their activities, and 77.5% had a BMI indicating overweight or higher. However, it is important to note that not every firefighting duty requires high fitness levels. The key is ensuring firefighters possess the fitness necessary for their specific roles to maintain safety and efficiency. The study aims to provide data for creating fitness management guidelines tailored to the diverse duties of firefighters.

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. Conclusion While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.