Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Background/Aims: Compared with other regimens, concomitant therapy (CT) used as a first-line regimen for Helicobacter pylori (H. pylori) infection is associated with higher eradication rates. We compared the efficacy of tailored therapy (TT) using bismuth added to standard triple therapy (STT) with CT. Methods: This consecutive study performed between September 2020 and 2021 included 210 patients with H. pylori infection. Two participating gastroenterologists prescribed TT and CT. Multiplex PCR assays were performed before eradication therapy to identify the relevant point mutations and confirm clarithromycin resistance in the TT group (n=105). Patients who showed negative PCR results received 14-day STT and those with positive PCR results received a 14-day regimen of bismuth added to STT. The other group (n=105) received 10-day CT. Results: Based on per-protocol analysis, eradication rates in the TT and CT groups were 89.2% (91/102) and 81.6% (84/103), respectively. We observed no statistically significant intergroup differences in eradication rates (P=0.12). The frequency of estimated clarithromycin resistance confirmed using multiplex PCR assays was 32.4% (34/105), and the eradication rate associated with bismuth add-on STT was 76.5% (26/34) in patients with clarithromycin resistance. Conclusions Considering the current and emerging trends in antibiotic resistance, a therapeutic strategy using TT (bismuth add-on STT) is recommended to minimize unnecessary administration of antibiotics.

Background/Aims: The effects of probiotic supplementation on Helicobacter pylori (H. pylori) eradication therapy are not completely understood. In this study, we investigated the effects of continuous probiotic administration on eradication rates, recrudescence, and symptom response following completion of a course of H. pylori therapy. Methods: This prospective, randomized, double-blind placebo-controlled trial was performed between June 2018 and 2020. Twohundred seventy patients who received a standard triple regimen for H. pylori eradication, were included in the study. Participants were randomized to receive a probiotic as adjunctive therapy (Enterococcus faecium 4.5×108 and Bacillus subtilis 5.0×107; Medilac-S®, Hanmi Pharmaceuticals, Seoul, Korea) or a placebo (one tablet thrice daily) for 28 days, following H. pylori eradication. Participants who showed successful eradication underwent a repeat 13C-urea breath test after 6 months. Results: Eradication rates in the probiotic and placebo groups were 77.1% and 72.4%, respectively (P=0.48) using per-protocol analysis. Using intention-to-treat analysis, eradication rates were 67.4% and 65.9%, respectively (P=0.43). Of 149 patients who were followed-up after 6 months, four patients had recrudescence (2.7%). Recrudescence rates did not differ between the probiotic and placebo groups. Of the 76 patients who had non-ulcer dyspepsia, 60 (78.9%) showed symptom resolution after 6 months. This beneficial effect was most pronounced in patients with postprandial distress syndrome (P=0.02). Conclusions Consecutive probiotic supplementation following H. pylori eradication therapy did not increase eradication rates or decrease recrudescence rates.

Background and Objectives: The de novo serine biosynthetic pathway from glucose has emerged as one of cancer metabolism; however, it is not explored the interplay between papillary thyroid cancer and metabolic flux of de novo serine synthesis. In this study, we explored the interplay between glucose utilization via GLUT1 expression and phosphoglycerate dehydrogenase (PHGDH). Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to determine the association between glucose importation and the serine metabolic pathway. The effects of glucose on serine biosynthesis and the role of PHGDH were investigated in papillary thyroid cancer cell lines. PHGDH and GLUT1 expression in 230 patients with papillary thyroid cancer (PTC) was explored using immunohistochemistry to explore the impact of the de novo serine biosynthetic pathway from glucose. Results: Glucose importation was significantly correlated with the serine biosynthetic and L-serine metabolic processes. Glucose uptake and serine synthesis were significantly increased and mitochondrial complex expression was upregulated in PTC cell lines grown in high-glucose media. Knockdown and inhibition of PHGDH decreased cell migration associated with glucose utilization. High PHGDH expression is significantly related with tumor aggressiveness and GLUT1 expression in patients with PTC. Conclusion In this study, we demonstrated that de novo serine biosynthesis from glucose is highly expressed in papillary thyroid cancer and associated with cancer cell metastasis through glucose utility. Our findings suggest the link between glucose utilization PHGDH to regulate tumor aggressiveness in PTC.

Objectives: The importance of public healthcare has been further emphasized by the arrival of the era of super-aged societies. This study investigates the landscape among oral health professionals, focusing on the concept development of the public oral health care (POHC) and essential oral health care (EOHC). Methods: A questionnaire survey of oral health professionals was conducted at six associations or societies who have an interest in POHC from December 21 to December 29, 2022. Chi-squared and logistic regression analyses were adopted to identify significant differences between the responses according to general characteristics. Significant differences were considered at a P-value of 0.05. Results: A total of 100 oral health professionals (48 dentists and 52 dental hygienists) participated in this study. The results revealed that there is a need for improvement of the POHC and the establishment of concepts related to the POHC and EOHC. The agreement rate was 90%, 85%, and 86% for the responsible organization, the target object and field, and the concept in the definition of the POHC, respectively. In the case of the construction of the EOHC, the agreement rate was 91% for “Quality of life,” and 85% for “Life and safety.” Among the community oral health programs as the POHC programs, “Oral health education program” showed the highest agreement rate. In healthcare institutions that are capable of providing the POHC services, “Oral health center in the public health center” had the highest agreement rate. Conclusions The POHC would be reasonable to define to ensure universal access to oral healthcare services for all citizens. In the case of EOHC, further research is needed to establish terminology and specific concepts in the future. This study could contribute valuable insights to the field of the POHC in an era of super-aged societies. As further research, more oral health professionals need to participate in the POHC-related policy and health care system.

Objective: Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. Methods: After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. Results: The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. Conclusion These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Objective: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. Methods: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. Results: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. Conclusion The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Background: We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. Methods: From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. Results: Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR group = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). Conclusion Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group.

Background: The aim of this study was to evaluate the association between near work time and depression. Methods: Data of 1,551 workers aged 19–49 years from the sixth Korea National Health and Nutrition Examination Survey were examined. The Patient Health Questionaire-9 scores were used to screen for depression. Participants who scored a total of 10 or above, which is suggestive of the presence of depression, were classified as the depression group; the rest were classified as normal. The correlation between daily near work time and depression was analyzed using multivariate logistic analysis after adjusting for other sociodemographic and health behavior-related variables. Results: Multivariate logistic analysis found that workers with 3 or more hours of near work were more likely to report depression compared to the reference group who had 2 or fewer hours per day of near work (adjusted odds ratio, 2.471; 95% confidence interval, 1.062–5.747). Conclusion Longer near work time was associated with depression among South Korea’s workers. Therefore, it is necessary to reduce near work time to prevent depression.

Purpose: The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction. Materials and methods: Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status. Results: Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05). Conclusion The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.