Identification of Small GTPases That Phosphorylate IRF3 through TBK1 Activation Using an Active Mutant Library Screen

Interferon regulatory factor 3 (IRF3) integrates both immunological and non-immunological inputs to control cell survival and death. Small GTPases are versatile functional switches that lie on the very upstream in signal transduction pathways, of which duration of activation is very transient. The large number of homologous proteins and the requirement for site-directed mutagenesis have hindered attempts to investigate the link between small GTPases and IRF3. Here, we constructed a constitutively active mutant expression library for small GTPase expression using Gibson assembly cloning. Small-scale screening identified multiple GTPases capable of promoting IRF3 phosphorylation. Intriguingly, 27 of 152 GTPases, including ARF1, RHEB, RHEBL1, and RAN, were found to increase IRF3 phosphorylation. Unbiased screening enabled us to investigate the sequence-activity relationship between the GTPases and IRF3. We found that the regulation of IRF3 by small GTPases was dependent on TBK1. Our work reveals the significant contribution of GTPases in IRF3 signaling and the potential role of IRF3 in GTPase function, providing a novel therapeutic approach against diseases with GTPase overexpression or active mutations, such as cancer.

MRI Findings of Renal Myxoma: A Case Report and Literature Review

Renal myxomas are very rare benign tumors. To date, a few cases have been reported in English literature, mostly in pathology and urology journals. Thus, there are few reports on the radiological findings associated with renal myxomas. We report on the imaging findings in a case of renal myxoma in a 62-year-old male. MRI demonstrated a well-defined mass in the left renal sinus, with intermediate high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumor showed gradual enhancement on contrast-enhanced T1-weighted images.

Ten-Year Prevalence Trends of Phenotypically Identified Community-Associated Methicillin-Resistant Staphylococcus aureus Strains in Clinical Specimens

Background@#Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains were first detected in hospitals in Korea between the late 2000s and early 2010s.However, there is limited information regarding the prevalence of CA-MRSA strains among hospital isolates and their phenotypic changes over the last decade. We investigated the prevalence trend of CA-MRSA strains isolated from different clinical specimens and their phenotypic changes between September 2009 and September 2019. @*Methods@#CA-MRSA strains were phenotypically identified by confirming their resistance to penicillin (PCN) and oxacillin (OXA) and evaluating their susceptibility to trimethoprimsulfamethoxazole, rifampin, fusidic acid, tetracycline, and at least one of the following four antimicrobials: clindamycin (CLI), erythromycin (ERY), ciprofloxacin (CIP), and gentamicin (GEN). A CA-MRSA strain that exhibited resistance to ERY, CLI, CIP, or GEN was classified as having resistance pattern I, II, III, or IV, respectively, regardless of its resistance to other antimicrobial agents. @*Results@#Of the 8,278 MRSA isolates identified in specimens obtained two days after admission, 1,385 (16.73%) were CA-MRSA strains. The prevalence of CA-MRSA strains increased from 12.2% to 26.6% (3.21% per period, P = 0.05). Resistance type analysis revealed an increasing trend in the prevalence of PCN/OXA-resistant (1.84%; P = 0.049) and PCN/OXA/ERY/CLI/CIP-resistant (0.98%; P = 0.04) CA-MRSA strains and in resistance pattern III strains (2.08%; P = 0.004). @*Conclusions@#The prevalence of CA-MRSA strains in Korea has increased significantly over the last decade, and CA-MRSA strains have gained phenotypic diversity beyond PCN/OXAresistance, including antimicrobial resistance to non-β-lactams, especially CIP.

Imaging Features and Interventional Treatment for Liver Injuries and Their Complications

Liver injury is a common consequence of blunt abdominopelvic trauma. Contrast-enhanced CT allows for the rapid detection and evaluation of liver injury. The treatment strategy for blunt liver injury has shifted from surgical to nonoperative management, which has been widely complemented by interventional management to treat both liver injury and its complications. In this article, we review the major imaging features of liver injury and the role of interventional management for the treatment of liver injury.

Comparison of CT Volumetry and RECIST to Predict the Treatment Response and Overall Survival in Gastric Cancer Liver Metastases

Purpose@#The aim of this study was to compare the diameter and volume of liver metastases on CT images in relation to overall survival and tumor response in patients with gastric cancer liver metastases (GCLM) treated with chemotherapy. @*Materials and Methods@#We recruited 43 patients with GCLM who underwent chemotherapy as a first-line treatment. We performed a three-dimensional quantification of the metastases for each patient. An independent survival analysis using the Response Evaluation Criteria in Solid Tumors (RECIST) was performed and compared to volumetric measurements. Overall survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios following univariate analyses. @*Results@#When patients were classified as responders or non-responders based on volumetric criteria, the median overall survival was 23.6 months [95% confidence interval (CI), 8.63–38.57] and 7.6 months (95% CI, 3.78–11.42), respectively (p = 0.039). The volumetric analysis and RECIST of the non-progressing and progressing groups showed similar results based on the Kaplan-Meier method (p = 0.006) and the Cox proportional hazard model (p = 0.008). @*Conclusion@#Volumetric assessment of liver metastases could be an alternative predictor of overall survival for patients with GCLM treated with chemotherapy.

Imaging Features and Interventional Treatment for Liver Injuries and Their Complications

Liver injury is a common consequence of blunt abdominopelvic trauma. Contrast-enhanced CT allows for the rapid detection and evaluation of liver injury. The treatment strategy for blunt liver injury has shifted from surgical to nonoperative management, which has been widely complemented by interventional management to treat both liver injury and its complications. In this article, we review the major imaging features of liver injury and the role of interventional management for the treatment of liver injury.

Comparison of CT Volumetry and RECIST to Predict the Treatment Response and Overall Survival in Gastric Cancer Liver Metastases

Purpose@#The aim of this study was to compare the diameter and volume of liver metastases on CT images in relation to overall survival and tumor response in patients with gastric cancer liver metastases (GCLM) treated with chemotherapy. @*Materials and Methods@#We recruited 43 patients with GCLM who underwent chemotherapy as a first-line treatment. We performed a three-dimensional quantification of the metastases for each patient. An independent survival analysis using the Response Evaluation Criteria in Solid Tumors (RECIST) was performed and compared to volumetric measurements. Overall survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios following univariate analyses. @*Results@#When patients were classified as responders or non-responders based on volumetric criteria, the median overall survival was 23.6 months [95% confidence interval (CI), 8.63–38.57] and 7.6 months (95% CI, 3.78–11.42), respectively (p = 0.039). The volumetric analysis and RECIST of the non-progressing and progressing groups showed similar results based on the Kaplan-Meier method (p = 0.006) and the Cox proportional hazard model (p = 0.008). @*Conclusion@#Volumetric assessment of liver metastases could be an alternative predictor of overall survival for patients with GCLM treated with chemotherapy.

Epidemiology of Burns in Infants: A Four-Year Retrospective Study

Usefulness of valacyclovir prophylaxis for cytomegalovirus infection after anti-thymocyte globulin as rejection therapy

BACKGROUND/AIMS@#Anti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy.@*METHODS@#We retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome.@*RESULTS@#Valacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis.@*CONCLUSIONS@#In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.

Modified composite graft using diced autogenous cartilage for amputated ear reconstruction: A case report

Trauma to the auricle is common given its prominent position, and various methods for ear reconstruction exist. Herein, we present our experience of ear reconstruction using diced autogenous cartilage. A 72-year-old woman fell from a 1-m height, damaging her ear in the process. The ear helix, which was approximately 3.5×3 cm² in size, was amputated. The cartilage was diced into 1-mm pieces. The detached skin was made into a pocket and filled with the diced cartilage. Molding was performed with tie-over dressings on the anterior and posterior areas of the scaphoid fossa. Ten days post-surgery, the wound showed signs of successful recovery, and the contour of the ear helix was maintained. Ten months later, the cartilage in the damaged ear helix was intact. Conventional composite grafts on amputated ears have size limitations and exhibit significant resorption, and loss of anatomical structures and stability often occur. In this case, the operating time required to complete the composite graft was short, and molding the contour was not complex. The original ear structure was maintained over the long term and did not require an additional operation for aesthetic purposes. We believe that this is a useful method for the reconstruction of an amputated ear.

Short-Term Success Rates of Smoking Cessation Support Programs and Factors Predicting Smoking Relapse: Using Data from a Smoking Cessation Clinic in a Hospital / 가정의학회지

BACKGROUND: Although the number of medical institutions running a smoking cessation clinic is on the rise, there remains a paucity of research on the long- and short-term success rates of smoking cessation programs, as well as on smoking relapse rates, before and after project implementation. This study assessed the general characteristics of patients visiting the smoking cessation clinic, success rate of smoking cessation in the short term, and risks of relapse. METHODS: Medical records from March 2015 to April 2017 were analyzed and telephone surveys were conducted with 151 smokers who visited a hospital smoking cessation clinic from March 2015 to April 2017. RESULTS: Of the 139 smokers who were eligible for follow-up, 22 (15.8%) failed to quit smoking initially. The clinic's 6-month success rate of smoking cessation was 64.83%. Those with higher medication compliance had a lower risk of primary failure (odds ratio, 0.056; 95% confidence interval, 0.005–0.609), whereas those with higher age (hazard ratio [HR], 0.128; P=0.0252) and a greater number of visits to the clinic (HR, 0.274; P=0.0124) had a lower risk of relapsing. CONCLUSION: The risk of primary failure to quit was higher with low medication compliance, and that of relapsing was higher with lower age and fewer number of clinic visits. Various evaluation and analysis methods can be carried out in the future based on the accumulated data for maintenance of smoking cessation and relapse prevention.

Rehabilitation of a patient with atrophic ridges using gothic arch tracing and nonpressure impression: a case report

Flabby ridges adversely affect the stability of complete dentures. For the management it is suggested that soft tissues reconditioned before making definitive dentures, and modified impression techniques used for the flabby ridges. Also, correct record of centric relation is important in complete dentures. This case of 67-year-old edentulous female patient had atrophied ridges on the mandible and the flabby ridge on the maxilla. Treatment dentures were fabricated using gothic arch tracing method and tissue conditioner. Definitive dentures were made using window opening impression technique, the gothic arch tracing method, and lingualized occlusion. The patient was satisfied with the function and esthetic quality of the new prostheses.

Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and sirolimus-induced diabetic rats

BACKGROUND/AIMS: Metformin (MET) is a first-line drug for type 2 diabetes mellitus (DM); its effect on new-onset diabetes after transplantation caused by immunosuppressant therapy is unclear. We compared the effects of MET on DM caused by tacrolimus (TAC) or sirolimus (SRL). METHODS: DM was induced by injection of TAC (1.5 mg/kg) or SRL (0.3 mg/kg) for 2 weeks in rats, and MET (200 mg/kg) was injected for 2 more weeks. The effects of MET on DM caused by TAC or SRL were evaluated using an intraperitoneal glucose tolerance test (IPGTT) and by measuring plasma insulin concentration, islet size, and glucose-stimulated insulin secretion (GSIS). The effects of MET on the expression of adenosine monophosphate-activated protein kinase (AMPK), a pharmacological target of MET, were compared between TAC- and SRL-treated islets. RESULTS: IPGTT showed that both TAC and SRL induced hyperglycemia and reduced plasma insulin concentration compared with vehicle. These changes were reversed by addition of MET to SRL but not to TAC. Pancreatic islet cell size was decreased by TAC but not by SRL, but addition of MET did not affect pancreatic islet cell size in either group. MET significantly increased GSIS in SRL- but not in TAC-treated rats. AMPK expression was not affected by TAC but was significantly decreased in SRL-treated islets. Addition of MET restored AMPK expression in SRL-treated islets but not in TAC-treated islets. CONCLUSIONS: MET has different effects on hyperglycemia caused by TAC and SRL. The discrepancy between these drugs is related to their different mechanisms causing DM.

Risks of borderline liver enzyme abnormalities to the incidence of impaired fasting glucose and diabetes mellitus: a 7 year follow up study of workers

BACKGROUND: The aim of this study was to identify the relationships between borderline serum liver enzyme abnormalities and the incidence of impaired fasting glucose (IFG) and diabetes mellitus (DM) during a 7-year follow-up of workers, and to evaluate the quantitative level of risks. METHODS: A total of 749 workers in an electronics manufacturing company were divided into the normal fasting blood glucose (n = 633), IFG (n = 98), and DM (n = 18) groups, according to the results of their health checkup in 2006. Among 633 workers in the normal group, excluding 55 workers who were impossible to follow, incidence rate and relative risks of 578 workers to the IFG or DM in 2013 according to the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (γ-GTP) were investigated. The liver enzyme levels were categorized as A (normal), B (borderline elevation), and R (definite elevation) following the standard of the National Health Insurance Service of Korea. RESULTS: The incidence rate of IFG or DM based on ALT level was 9.7 % for the A, 30.0 % for B, and 15.4 % for R. According to γ-GTP, the incidence rate was 9.8 % for A, 34.5 % for B, and 25.0 % for R. The relative risk(RR) to the incidence of IFG or DM depending on the level of ALT were 3.09 in B and 1.59 in R compared to A. According to γ-GTP, RR was 3.52 in B and 2.55 in R compared to A. AST level was not related to the incidence of IFG or DM. A multiple logistic regression analysis with the incidence of IFG or DM as a dependent variable resulted in an odds ratio of 2.664(1.214–5.849) for B level ALT, 3.685(1.405–9.667) for B level of γ-GTP even after adjustment for other variables such as age, sex, body mass index, AUDIT score, systolic blood pressure, and triglyceride. CONCLUSIONS: Even borderline elevations of ALT and γ-GTP, but not AST, increased the incidence and risk of IFG or DM after 7 years. Borderline elevation of ALT and γ-GTP was identified as an independent risk factor of IFG or DM.

Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

BACKGROUND/AIMS: Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods. METHODS: Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction. The safety of SRL conversion was assessed considering thegraft function, acute rejection, and graft loss. Immunologic alterations were measuredvia serial changes of T cell and B cell subsets after SRL conversion. Adverseeffects of SRL conversion were also evaluated. RESULTS: Conversion to SRL was successful in nine patients (64.2%). Conversionto SRL preserved graft function as compared to the baseline value (p = 0.115). Noacute rejection or allograft loss was observed during the follow-up period. Immunemonitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRLconversion, and oral mucositis was the main cause of SRL withdrawal. CONCLUSIONS: Conversion to SRL can be safe and has immunologic benefits in KTrecipients with long-term CNI exposure. Close monitoring of mucocutaneous adverseevents is, however, required in the early period after SRL conversion.

Limited immune tolerance induced by transient mixed chimerism

No abstract available.

Relationship between adhering to dietary guidelines and the risk of obesity in Korean children

BACKGROUND/OBJECTIVES: Dietary guidelines for Korean children were released in 2009. The goal of the present study was to examine diet quality in terms of adherence to these dietary guidelines as well as explore the association between guideline adherence and risk of obesity in Korean children. SUBJECTS/METHODS: Children aged 5-11 years (mean age = 8.9 years old, n = 191, 80.6% girls) were recruited from a university hospital in Seoul, Korea. Adherence to dietary guidelines for Korean children was calculated using the Likert scale (1-5), and children were then categorized into low, moderate, and high groups based on adherence scores. Obesity or being overweight was determined based on an age- and gender- specific percentile for body mass index (BMI) of the 2007 Korean National Growth Charts. Diet quality was evaluated from 3 days of dietary intake data. RESULTS: Children in the high adherence group were characterized by significantly lower BMI percentiles and paternal BMIs as well as higher percentages of fathers with a high level of education and higher household incomes compared to those in the low or moderate group. Children in the high adherence group consumed significantly higher amounts of milk and dairy products, were less likely to consume lower than the EAR of phosphorus and iron, and had higher NARs for calcium, phosphorus, iron, zinc, and MAR than those in low groups. The ORs for obesity (BMI > or = 95th percentile) or being overweight including obesity (BMI > or = 85th percentile) were significantly lower in the high adherence group compared to the low adherence group (OR: 0.33, 95% CI = 0.13-0.82, P for trend = 0.019; OR: 0.26, 95% CI: 0.11-0.61 P for trend = 0.002). CONCLUSIONS: Korean children who adhered to dietary guidelines displayed better diet quality and a reduced risk of obesity.

Acute health effects of accidental chlorine gas exposure

OBJECTIVES: This study was conducted to report the course of an accidental release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on March 5, 2013. We describe the analysis results of 2 patients hospitalized because of chlorine-induced acute health problems, as well as the clinical features of 209 non-hospitalized patients. METHODS: We analyzed the medical records of the 2 hospitalized patients admitted to the hospital, as well as the medical records and self-report questionnaires of 209 non-hospitalized patients completed during outpatient treatment. RESULTS: Immediately after the exposure, the 2 hospitalized patients developed acute asthma-like symptoms such as cough and dyspnea, and showed restrictive and combined pattern ventilatory defects on the pulmonary function test. The case 1 showed asthma-like symptoms over six months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2, his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%). Both cases were diagnosed as chlorine-induced reactive airways dysfunction syndrome (RADS) on the basis of these clinical features. The most frequent chief complaints of the 209 non-hospitalized patients were headache (22.7%), followed by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with asymptomatic patients accounting for 36.5%. The multiple-response analysis of individual symptom revealed headache (42.4%) to be the most frequent symptom, followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea (27.6%), and dizziness (27.3%). CONCLUSIONS: The 2 patients hospitalized after exposure to chlorine gas at the leakage site showed a clinical course corresponding to RADS. All of the 209 non-hospitalized patients only complained of symptoms of the upper airways and mucous membrane irritation.

Recurrent neutropenia induced by rifabutin in a renal transplant recipient

No abstract available.

Hazard Classification of Household Chemical Products in Korea according to the Globally Harmonized System of Classification and labeling of Chemicals

OBJECTIVES: This study was conducted to review the validity of the need for the application of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) to household chemical products in Korea. The study also aimed to assess the severity of health and environmental hazards of household chemical products using the GHS. METHODS: 135 products were classified as 'cleaning agents and polishing agents' and 98 products were classified as 'bleaches, disinfectants, and germicides.' The current status of carcinogenic classification of GHS and carcinogenicity was examined for 272 chemical substances contained in household chemical products by selecting the top 11 products for each of the product categories. In addition, the degree of toxicity was assessed through analysis of whether the standard of the Republic of Korea's regulations on household chemical products had been exceeded or not. RESULTS: According to GHS health and environmental hazards, "acute toxicity (oral)" was found to be the highest for two product groups, 'cleaning agents and polishing agents', and 'bleaches, disinfectants, and germicides' (result of classification of 233 household chemical products) at 37.8% and 52.0% respectively. In an analysis of carcinogenicity assuming a threshold of IARC 2B for the substances in household chemical products, we found 'cleaning agents and polishing agents' to contain 12 chemical substances and 'bleaches, disinfectants, and germicides' 11 chemical substances. CONCLUSION: Some of the household chemical products were found to have a high hazard level including acute toxicity and germ cell mutagenicity, carcinogenicity, and reproductive toxicity. Establishing a hazard information delivery system including the application of GHS to household chemical products in Korea is urgent as well.