Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Background: Obesity and weight loss are associated with increased mortality. Understanding the association between weight change and mortality is critical and can help inform effective prevention and intervention strategies. Therefore, this study aimed to investigate the association between weight change and mortality based on body mass index (BMI) intervals using data from a 12-year follow-up survey in Korea. Methods: We used data from the Korean Longitudinal Study of Aging from 2006 to 2018. Individuals aged 45–69 years without a history of malignancy and chronic obstructive pulmonary disease at baseline were selected. Cox regression analysis was used to compare mortality based on body mass index and weight change. Results: Compared with individuals with a body mass index of 20.0–25.0 kg/m2 and an increase in body weight of <5 kg, mortality was 3.8 times higher in the group with a body mass index of <20.0 kg/m2 and a weight loss of <5 kg, two times higher in the group with a body mass index of 20.0–25.0 kg/m2 and weight loss of >10 kg, and 4.3 times higher in the group with a body mass index of ≥25.0 kg/m2 and weight gain of ≥10 kg. Conclusions Weight loss in underweight or normal-weight individuals and weight gain in individuals with obesity increased the mortality rate compared with individuals with normal weight and less weight change. This suggests that body weight and the changes in the weight of individuals are crucial, and weight loss in patients with underweight and weight gain in patients with obesity are closely related to increased mortality.

Background/Aims: Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the longterm outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean followup duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusions Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Since the late 1990s, online e-learning has offered unparalleled convenience and affordability, becoming increasingly popular among pathologists. Traditional learning theories have been successfully applied to web/mobile-based learning systems, with mobile technologies even enhancing conventional offline education. In cytopathology, hands-on microscope training has traditionally been paramount, complemented by real-case presentations and lectures. However, the coronavirus disease 2019 (COVID-19) pandemic disrupted regular academic activities, making online e-learning platforms essential. We designed a web/mobile-based learning platform to enhance continued medical education in cytopathology at various levels, particularly during the era of COVID-19 and beyond. Since 2021, we have integrated curriculum materials, virtual education files, and whole-slide images (WSIs) of cytopathology, submitted from over 200 institutions across Korea, with the support of numerous instructors. We develop a new e-learning platform named “CytoAcademy” composed of a basic session for each organ and level across the range of morphologic findings; on-demand lectures to enhance cytopathologic knowledge; WSI archives that allow users to explore various histologically confirmed cases; and a self-assessment test to help organize diagnostic knowledge acquired through the web/mobile-friendly learning system. The platform provides not just an opportunity to achieve a correct diagnosis, but also a learning experience based on problem-solving point. Members interact, identify their deficiencies, and focus on specific educational materials. In this manner, all participants can actively engage in creating and maintaining knowledge and foster a proactive approach to learning.

This study aims to provide basic data for developing home meal replacement (HMR) products and establishing marketing strategies in Thailand. A survey was conducted targeting Thai consumers who have experience using HMR regularly. The food consumption values were used to segment the Thai consumer market, and the differences in HMR purchase behavior were analyzed according to segment. Thai consumers were divided into three types: high, medium, and low interest in food habits. The main reasons for using HMR among Thai consumers were time-saving, convenience, and cost-effectiveness, with a strong preference for products with high convenience. Among the HMR selection attributes, items such as quality, expiration date, hygiene, safety, taste, nutrition, and freshness are generally important factors for consumers. Among the HMR selection attributes, the items that require improvement first were identified most frequently in the high-interest food lifestyle group and include quality, quantity, additives, ingredients, expiration date, and nutrients. This study is significant because it was conducted targeting the Thai HMR market, where research has been limited, and it revealed the characteristics of segmented markets by reflecting the food consumption value characteristics of Thai consumers. The characteristics of each market segment can be used to develop HMR and marketing strategies that fit the market.