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Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an indepth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.
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Objective@#This study examined the difference in procalcitonin between sepsis and septic shock. @*Methods@#The single-center retrospective cohort study was conducted from July 2017 to June 2018 at an emergency department (ED) of a university hospital. The inclusion criteria were patients over 18 years old who visited the ED with an infection. The exclusion criteria were the patients without organ failure by sepsis-3 definition, those with missing serum lactate data, and those discharged without workup. The sepsis patients were divided into those with and without septic shock, and the two groups were compared with biomarkers, including procalcitonin. @*Results@#Of the 406 patients who visited the ED with an infection, 36 were excluded because they did not have sepsis or an unknown infection. Finally, 369 patients were enrolled, and 61.5% fitted the septic shock definition. A comparison of the septic shock and non-shock sepsis groups showed that a history of chronic liver disease, malignancy, pulse rate, prothrombin time, blood urea nitrogen, aspartate and alanine transaminase, troponin-I, Sequential Organ Failure Assessment score and procalcitonin levels were significantly higher in the septic shock group. In multivariate analysis, however, procalcitonin was an independent predictor for septic shock (adjusted odd ratio, 1.05; 95% confidential interval, 1.01-1.09). The area under the receiver operating characteristic curve was 0.729, and the cutoff value was 4.0 ng/mL. @*Conclusion@#The procalcitonin levels were higher in the septic shock group than in the non-shock sepsis group. This could help predict septic shock independently. Further prospective multicenter research is needed to determine if procalcitonin can predict the severity of sepsis.
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BACKGROUND@#Cryopreservation can cause mechanical and chemical stress, ultimately leading to the formation of reactive oxygen species (ROS) and oxidative stress. ROS inhibits the expression of antioxidant enzymes in cells, resulting in increased DNA fragmentation and apoptosis. In this paper, we used a vitrification method that has the advantage of producing less ice crystal formation, cost-effectiveness, and time efficiency during cryopreservation. The objective of this paper is to evaluate the degree of protection of ovarian tissue against oxidative stress when N-acetylcysteine (NAC) and Klotho proteins are treated in the vitrification process of ovarian tissue. @*METHODS@#The control group and the cryopreservation groups were randomly assigned, and treated NAC, Klotho, or the combination (NAC ? Klotho). The cell morphological change, DNA damage, senescence, and apoptosis of each group after the freeze–thaw process were compared using transmission electron microscopy, immunohistochemistry, and western blot analysis. @*RESULTS@#Both NAC and Klotho were found to be more effective at protecting against DNA damage than the control;however, DNA damage was greater in the NAC ? Klotho group than in the group treated with NAC and Klotho, respectively. DNA damage and cellular senescence were also reduced during the vitrification process when cells were treated with NAC, Klotho, or the combination (NAC ? Klotho). NAC increased apoptosis during cryopreservation, whereas Klotho inhibited apoptosis and NAC-induced apoptosis. @*CONCLUSION@#This study highlights Klotho’s benefits in inhibiting DNA damage, cell senescence, and apoptosis, including NAC-induced apoptosis, despite its unclear role in vitrification.
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Schaaf-Yang syndrome (SYS) is a rare genomic imprinting disorder caused by truncating mutations in the paternally derived MAGE family member L2 (MAGEL2) allele. It is also responsible for Prader-Willi syndrome, characterized by neonatal hypotonia, developmental delay, intellectual disability, respiratory distress in early infancy, and arthrogryposis. More than 250 individuals with approximately 57 different molecular variants have been reported since 2013, but the phenotype-genotype association in SYS is not yet fully understood. Here, we describe the case of a Korean patient diagnosed with SYS harboring a mutation in the paternal allele of MAGEL2: c.2895G>A, resulting in a protein change of p.Trp965*. The patient’s phenotype included respiratory distress, arthrogryposis, hypotonia, and feeding difficulty in the early neonatal period. Mild renal dysfunction and hearing impairment were observed during infancy.
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Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.
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Objective@#Peritonitis is a life-threatening, emergent surgical disease with very high mortality and morbidity. Currently, there are insufficient Korean studies using the P-POSSUM (Portsmouth-Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) and the Mannheim Peritonitis Index (MPI) as risk prediction models for nontraumatic peritonitis patients who visit the emergency room. @*Methods@#This retrospective study was carried out on 196 cases of non-traumatic peritonitis in a single emergency center from January 2015 to December 2019. Receiver operating characteristic (ROC) curves were obtained and the area under the ROC curve (AUC) was compared using both P-POSSUM and MPI. The observed mortality and expected mortality for P-POSSUM were compared using the goodness of fit assessed using the Hosmer-Lemeshow equation. @*Results@#Diastolic blood pressure, blood urea nitrogen, potassium, length of stay, and intensive care unit admissions were significantly different between survivors and non-survivors. The AUC was 0.812 for P-POSSUM and 0.646 for MPI. The observed-to-expected mortality ratio for P-POSSUM indicated fewer than expected deaths in all quintiles of risk and this was more pronounced, especially when the expected mortality was over 60%. @*Conclusion@#In non-traumatic peritonitis patients, P-POSSUM was more useful in predicting risk than the MPI score. However, P-POSSUM overestimated the risk in high-risk patients. Although the MPI score is only somewhat useful for predicting mortality in patients with non-traumatic peritonitis, it is useful as an adjuvant.
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Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.
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The purpose of this study was to develop prototype of virtual reality(VR) simulation with malocclusion models and evaluate its applicability. Task abilities, task completion time, and a satisfaction survey were compared between dentist trainees and dental students. Participants were instructed to observe virtual malocclusion models and then performed three tasks to diagnose the type of malocclusion, determine clinical findings and develop treatment plans. Their satisfaction with the simulation experience were evaluated using a questionnaire containing five questions. Task abilities of trainees related to clinical features and treatment plans were significantly higher than that of students(p < 0.01). In both groups, the task completion time for the second case was significantly reduced compared to that for the first case(p < 0.01). The satisfaction survey showed high scores and positive responses for this simulation in both groups. If the prototype of VR simulation is continuously advanced, it will be applicable for orthodontic education in pediatric dentistry.
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Background@#Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. @*Methods@#Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. @*Results@#Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. @*Conclusions@#In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.
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Background@#Common bile duct (CBD) stone is one of the most prevalent gastroenterological diseases, but the role played by biliary microbiota in the pathogenesis of CBD stones remains obscure. The aim of this study was to investigate the characteristics of the biliary tract core microbiome and its potential association with the formation of pigment stones. @*Methods@#Twenty-eight patients with biliary obstruction of various causes were enrolled.Thirteen had new-onset pigment CBD stone. Of the remaining 15, four had benign biliary stricture, four had gallbladder cancer, three had pancreatic cancer, 3 had distal CBD cancer, and one had hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography was used to collect bile samples for DNA extraction, 16S ribosomal RNA gene sequencing, and bile microbiota composition analysis. @*Results@#Proteobacteria (61.7%), Firmicutes (25.1%), Bacteroidetes (5%), Fusobacteria (4.6%), and Actinobacteria (2.6%) were the most dominant phyla in the bile of the 28 study subjects. A comparison between new-onset choledocholithiasis and other causes of biliary obstruction (controls) showed Enterococcus was found to be significantly abundant in the CBD stone group at the genus level (linear discriminant analysis score = 4.38; P = 0.03). However, no other significant compositional difference was observed. @*Conclusion@#This study demonstrates an abundance of microbiota in bile juice and presents a biliary microbiome composition similar to that of duodenum. The study also shows Enterococcus was significantly abundant in the bile juice of patients with a brown pigment stone than in controls, which suggests Enterococcus may play an important role in the development of pigment stones.
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Background@#Common bile duct (CBD) stone is one of the most prevalent gastroenterological diseases, but the role played by biliary microbiota in the pathogenesis of CBD stones remains obscure. The aim of this study was to investigate the characteristics of the biliary tract core microbiome and its potential association with the formation of pigment stones. @*Methods@#Twenty-eight patients with biliary obstruction of various causes were enrolled.Thirteen had new-onset pigment CBD stone. Of the remaining 15, four had benign biliary stricture, four had gallbladder cancer, three had pancreatic cancer, 3 had distal CBD cancer, and one had hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography was used to collect bile samples for DNA extraction, 16S ribosomal RNA gene sequencing, and bile microbiota composition analysis. @*Results@#Proteobacteria (61.7%), Firmicutes (25.1%), Bacteroidetes (5%), Fusobacteria (4.6%), and Actinobacteria (2.6%) were the most dominant phyla in the bile of the 28 study subjects. A comparison between new-onset choledocholithiasis and other causes of biliary obstruction (controls) showed Enterococcus was found to be significantly abundant in the CBD stone group at the genus level (linear discriminant analysis score = 4.38; P = 0.03). However, no other significant compositional difference was observed. @*Conclusion@#This study demonstrates an abundance of microbiota in bile juice and presents a biliary microbiome composition similar to that of duodenum. The study also shows Enterococcus was significantly abundant in the bile juice of patients with a brown pigment stone than in controls, which suggests Enterococcus may play an important role in the development of pigment stones.
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Background@#Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. @*Methods@#Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. @*Results@#Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. @*Conclusions@#In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.
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Background@#Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation. @*Methods@#Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value:high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, posttransplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups. @*Results@#Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or posttransplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015). @*Conclusion@#High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.
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Background@#Prevention of osteoporosis and bone fracture is one of the important issues for liver transplant recipients because a long history of liver disease and lifelong use of immunosuppressants, including corticosteroids, may cause these diseases. In this study, we aimed to analyze liver recipient bone status, 10-year fracture risk, and medication history. @*Methods@#The electronic medical records of adult patients aged >40 years who received liver transplantation at Seoul National University Bundang Hospital between January 2009 and June 2017 were reviewed retrospectively. On the basis of their bone mineral density and fracture history, their fracture risks were analyzed using the Korean fracture risk assessment tool. @*Results@#A total of 57 liver transplant recipients were treated with corticosteroids during a mean of 8.8 months after transplantation. 30 patients (52.6%) showed bone metabolism dysfunction such as osteopenia or osteoporosis. The 10-year femoral fracture risk was 2.1%, and dual-energy X-ray absorptiometry monitoring was performed, including right before liver transplantation every 27.5±19.2 months. The mean femoral bone mineral density decreased by −7.2%±7.3%. Four patients (7.0%) had a fracture after liver transplantation. Osteoporotic fracture occurred in 3 patients with osteoporosis (25.0%). Among the osteopenia patients with moderate fracture risk who were not treated with bisphosphonate, 1 patient (12.5%) had a history of bone fracture after liver transplantation. @*Conclusions@#Considering the deterioration of bone density and moderate fracture risk, medication for osteoporosis should be prescribed to liver transplant recipients with regular monitoring of bone density after transplantation.
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This study was undertaken to provide basic data for revitalizing the school meal support centers and improvingschool meals, by analyzing the purchase conditions and satisfaction of food according to an adoptionof a school meal service support center. Comparing the purchasing efficiency, convenience to purchase, andhigher overall satisfaction was achieved when a school meal service support center was adopted by the localgovernment, as compared to non-adopted school meal service support centers. Therefore, it is considered thatthe adaption of a school meal service support center is urgently required by non-adoption local governments.Moreover, the stability of food material supplies was also higher in the adopted rather than the non-adoptedcenters. Satisfaction with the quality of food ingredients was also found to be significantly higher in theadopted centers. These results indicate that if the local government adopts and introduces the school mealsupport center, inconsistencies observed in the return and exchange processes experienced by the non-adoptedcenters can be resolved, and food quality satisfaction can be improved. We, therefore, propose the necessityto implement a system for determining reasonable pricing by establishing systematic cooperation amongschools, manufacturing entities (suppliers), and the School Meal Service Support Center.
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This study was undertaken to optimize preparation of sweet rice muffins using lotus (Nelumbo nucifera Gaertn) seed powder. The experimental conditions used in the preparation included lotus seed powder (X1) and soybean oil (X2). The muffin formulation was optimized using rheology. Lightness (P<0.01) displayed a quadratic model pattern, whereas yellowness (P<0.01) and redness (P<0.05) was presented a linear model. Texture properties significantly differed in cohesiveness (P<0.05). Evaluating the sensory characteristics of muffins, except for flavor and texture, the remaining properties of color (P<0.01), taste, overall quality, and appearance (P<0.05) were found to be significantly different. The overall quality was also affected by the proportion of lotus seed powder, rather than the amount of soybean oil. The optimal ratio for palatability of muffins was determined to be 47.80 g lotus seed powder and 95.28 g soybean oil. Taken together, our results indicate that sweet rice muffins prepared using lotus seed powder are sufficiently competitive in terms of function and quality.
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Background@#Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation. @*Methods@#Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value:high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, posttransplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups. @*Results@#Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or posttransplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015). @*Conclusion@#High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.
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Background@#Prevention of osteoporosis and bone fracture is one of the important issues for liver transplant recipients because a long history of liver disease and lifelong use of immunosuppressants, including corticosteroids, may cause these diseases. In this study, we aimed to analyze liver recipient bone status, 10-year fracture risk, and medication history. @*Methods@#The electronic medical records of adult patients aged >40 years who received liver transplantation at Seoul National University Bundang Hospital between January 2009 and June 2017 were reviewed retrospectively. On the basis of their bone mineral density and fracture history, their fracture risks were analyzed using the Korean fracture risk assessment tool. @*Results@#A total of 57 liver transplant recipients were treated with corticosteroids during a mean of 8.8 months after transplantation. 30 patients (52.6%) showed bone metabolism dysfunction such as osteopenia or osteoporosis. The 10-year femoral fracture risk was 2.1%, and dual-energy X-ray absorptiometry monitoring was performed, including right before liver transplantation every 27.5±19.2 months. The mean femoral bone mineral density decreased by −7.2%±7.3%. Four patients (7.0%) had a fracture after liver transplantation. Osteoporotic fracture occurred in 3 patients with osteoporosis (25.0%). Among the osteopenia patients with moderate fracture risk who were not treated with bisphosphonate, 1 patient (12.5%) had a history of bone fracture after liver transplantation. @*Conclusions@#Considering the deterioration of bone density and moderate fracture risk, medication for osteoporosis should be prescribed to liver transplant recipients with regular monitoring of bone density after transplantation.
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This study examined the subjective health recognition, motivation, selection property, consumption realties, and generalities of elderly people eating out. The ratio of women eating out in those over 60 years of ages was high and people in that age group ate out most actively. The score of convenience-oriented, gourmet-oriented, and dignity-oriented of the selection property for eating out increased with increasing frequency and expenditure for eating out. With increasing age, a negative (−) relationship with a decrease in the safety-oriented score of the selection property for eating out was predicted. As the number of days eating out increased, a positive (+) relationship with an increase in the safety-oriented score of the selection property for eating out was observed. As the scores of physical and social health perception increased, a positive (+) relationship with an increase in the gourmet oriented score was observed. Based on the results, various research on the relationship between the health recognition and eating out behavior of those over 60 years of age are required.