Purpose: Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%). Materials and Methods: Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA. Results: The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84). Conclusion Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.

Objectives: Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase enzyme in the liver and then acetaldehyde is metabolized to acetone by aldehyde dehydrogenase (ALDH) in the liver. There are two main ALDH enzymes which metabolize the acetaldehyde produced during ethanol oxidation. In particular, in the presence of the ALDH2 1*2 allele, the activity of the ALDH 2 enzyme is lowered. As a result, acetaldehyde metabolism is slowed down and acetaldehyde accumulates in the body compared to the ALDH2 1*1 allele. There are many studies that have investigated the blood acetaldehyde concentration according to the ALDH2 genotype, but there are few studies to compare this with age. So we investigated the blood acetaldehyde concentration according to ALDH2 genotype, age and gender. Methods: According to the ALDH2 genotype, we divided the group by gender and age. We divided the age group in to three groups which ranged from 20 to 34 years old, from 35 to 49 years old, and lastly from 50 to 64 years old. And then we collected blood samples after 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr and 15 hr of after drinking to measure the blood acetaldehyde concentration. Results: In ALDH2 1*2 allele group, there are significant differences of the blood acetaldehyde concentration between the age groups. In ALDH2 1*2 allele and male group, there are significant differences of the blood acetaldehyde concentration between the age groups. Conclusions There are significant differences of the blood acetaldehyde concentration between the age groups according to ALDH2 genotype. Also, there are significant differences of the blood acetaldehyde concentration between the age groups with male gender and ALDH2 1*2 allele. Studies about other factors that may influence the blood acetaldehyde concentration are needed.

Objectives: The effectiveness of drugs currently used in medication, which is important in the treatment of alcohol use disorders, is limited. Recently, ondansetron which acts as 5-HT3 receptor antagonist, has been studied and proved possibility as new medication for alcohol use disorder. Meanwhile, there are studies supporting that 5-HT1A receptors are related to addictive behavior. Considering those studies, we expect that vortioxetine, which acts as both 5-HT3 receptor antagonist and 5-HT1A receptor agonist, may be effective in treatment of alcohol use disorder. The purpose of this study is to examine the effect of vortioxetine on alcohol intake of C57BL/6 mice. Methods: In this study C57BL/6 mice were randomly assigned to normal saline group, vortioxetine 10 mg/kg group and vortioxetine 1 mg/kg group. To study effect of vortioxetine on alcohol, water, food intake and body weight of mice, we administered each medication for 14 days. Results: The overall alcohol intake was different between the three groups (PGroup=0.021), and alcohol intake in vortioxetine 10 mg/kg group was significantly lower than one in placebo group. Change across time points (PTime<0.001) and the interaction between group and time (PGroup×Time =0.016) were also significant. However, there were no significant differences between the three groups in water, food intake and body weight. Conclusions These results indicated that administration of high dose vortioxetine reduced alcohol intake of mice.Therefore, it is necessary to conduct clinical studies to examine the effectiveness of vortioxetine as a new treatment for alcohol use disorder.

Implant prostheses and removable partial dentures are mainly used as treatment methods for partial edentulous patients who have lost a number of teeth. The implant-assisted removable partial denture (IARPD) is strategically selected. The defect in maxillofacial structure due to osteomyelitis, a type of facial bone infection, causes dysfunction such as mastication, swallowing, and pronunciation, as well as social and psychological effects, so a removable restoration is required to restore the supporting tissue. Design of abutment and partial dentures is an essential factor in the success of treatment. In this case, IARPD, which has superior retention and stability compared to traditional removable partial dentures, can have a good prognosis. In a partial edentulous patient with bone defects due to osteomyelitis treatment, the stability of the denture was secured with IARPD restoration. Moreover, maintenance problem that may occur in the future was minimized by providing an appropriate denture design and occlusal scheme through several provisional restorations. This case can be expected to have a favorable prognosis in the long term.

Implant prostheses and removable partial dentures are mainly used as treatment methods for partial edentulous patients who have lost a number of teeth. The implant-assisted removable partial denture (IARPD) is strategically selected. The defect in maxillofacial structure due to osteomyelitis, a type of facial bone infection, causes dysfunction such as mastication, swallowing, and pronunciation, as well as social and psychological effects, so a removable restoration is required to restore the supporting tissue. Design of abutment and partial dentures is an essential factor in the success of treatment. In this case, IARPD, which has superior retention and stability compared to traditional removable partial dentures, can have a good prognosis. In a partial edentulous patient with bone defects due to osteomyelitis treatment, the stability of the denture was secured with IARPD restoration. Moreover, maintenance problem that may occur in the future was minimized by providing an appropriate denture design and occlusal scheme through several provisional restorations. This case can be expected to have a favorable prognosis in the long term.

The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.
Adult ; Asian People/genetics* ; Azoospermia/genetics* ; Case-Control Studies ; Cell Cycle Proteins/genetics* ; Gene Expression Regulation/genetics* ; Genotype ; Haplotypes ; Humans ; Male ; MicroRNAs/genetics* ; Oligospermia/genetics* ; Polymorphism, Single Nucleotide ; RNA, Messenger ; Republic of Korea ; Spermatogenesis/genetics*

PURPOSE: Patients in the intensive care unit (ICU) are more susceptible to nosocomial infections, including central line-associated bloodstream infection (CLABSI), surgical site infection, urinary tract infection or ventilator-associated pneumonia. This study is a comparative analysis of how central venous catheter (CVC) management staff affects CLABSI. METHODS: We performed a two-phase review of all patients transferred to the surgical ICU (SICU) from January 2013 to June 2014. CVC management staff was introduced in October 2013. Electronic medical records provided the data for a comparative analysis of incidence rates and risks of CLABSI, as well as the subjects' general characteristics. RESULTS: This study included 248 patients before the introduction of a CVC management staff member and 196 patients after the introduction. General patient characteristics before and after the CVC management staff was in place did not differ significantly. The CLABSI rate decreased by 4.61 cases/1,000 device days after the introduction (6.26 vs. 1.65; odds ratio, 4.47; 95% confidence interval, 1.39~14.37; p=0.009). However, the mortality rate and length of ICU stay did not change after CVC management staff was in place (12.9% vs. 10.7%, p=0.480; 16.00±24.89 vs. 15.87±18.80, p=0.954; respectively). CONCLUSION: In this study, the introduction of CVC management staff effectively reduced CLABSI rates in current ICU system.
Central Venous Catheters* ; Critical Care* ; Cross Infection ; Electronic Health Records ; Humans ; Incidence ; Intensive Care Units ; Mortality ; Odds Ratio ; Pneumonia, Ventilator-Associated ; Surgical Wound Infection ; Urinary Tract Infections

PURPOSE: We examined the prevalence and CGG/AGG repeat structure of expanded alleles of the FMR1 gene in preconceptional and pregnant Korean women. MATERIALS AND METHODS: The CGG repeats in the FMR1 genes of 1,408 women were analyzed by polymerase chain reaction and Southern blot analysis. To estimate the prevalence of expansion alleles, the individuals were divided into low risk and high risk group. RESULTS: Within this population, 98.4% had normal alleles and 1.6% had abnormal alleles including intermediate (0.6%), premutation (0.5%), full mutation (0.1%), and hemizygous (0.4%) alleles. There were 2 premutation alleles (1:666, 95% confidence interval [CI] 1:250-1,776) in the low risk group and 5 premutation alleles (1:15, 95% 1:6-36) in the high risk group. There were 8 intermediate alleles (1:167, 95% CI 1:130-213) in the low risk group and 1 intermediate alleles (1:76, 95% CI 1:11-533) in the high group. Six of the 7 premutation alleles did not contain AGG interruptions within the repeats and 1 had a single AGG interruption. Four of the 9 intermediate alleles contained 2-3 AGG, 4 had a single AGG, and 1 had no AGG interruptions. CONCLUSION: Our study demonstrates the prevalence and CGG/AGG structure of expansion alleles in Korean women. The identified premutation prevalence is higher than that of other Asian populations and lower than that of Caucasian populations. Although our study is limited by size and population bias, our findings could prove useful for genetic counseling of preconceptional or pregnant women.
Alleles ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Blotting, Southern ; Carrier State ; Female ; Fragile X Syndrome ; Gene Frequency ; Genetic Counseling ; Humans ; Mass Screening* ; Polymerase Chain Reaction ; Pregnant Women ; Prevalence ; Trinucleotide Repeat Expansion

PURPOSE: We aimed to evaluate the use and safety of double dose oseltamivir for patients manifesting severe respiratory symptoms or showing no improvement of clinical symptoms after 72 hours' treatment with the usual oseltamivir dosage. METHODS: We analyzed the clinical features of 2009 influenza A H1N1 inpatients who had been admitted to a university hospital's Department of Pediatrics between August 2009 and January 2010. The Influenza A H1N1 diagnoses were confirmed by real-time reverse transcriptase polymerase chain reaction. RESULTS: The study participants numbered 157 (mean age, 5.0 years; male-to-female ratio, 1.1:1). Among them, twenty (mean age, 5.2 years) were administered double dose oseltamivir. This double dose group showed higher peak body temperatures and more abnormal radiologic results than the other, usual-dose group. The mean time duration between high fever and afebrile status after initiation of double-dose oseltamivir administration was 2.1 days, whereas that within the usual-dose group was 1.7 days. There were no adverse effects in the patients treated with double-dose oseltamivir. CONCLUSION: Double-dose oseltamivir was well tolerated in patients with severe 2009 influenza A H1N1 infection.
Body Temperature ; Diagnosis ; Fever ; Humans ; Influenza A virus ; Influenza, Human* ; Inpatients ; Oseltamivir* ; Pandemics* ; Pediatrics ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index

Gitelman syndrome is a rare autosomal recessive hereditary salt-losing tubulopathy, that manifests as hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is caused by mutations in the solute carrier family 12(sodium/chloride transporters), member 3 (SLC12A3) gene encoding the thiazide-sensitive sodium chloride cotransporter channel (NCCT) in the distal convoluted tubule of the kidney. It is associated with muscle weakness, cramps, tetany, vomiting, diarrhea, abdominal pain, and growth retardation. The incidence of growth retardation, the exact cause of which is unknown, is lower than that of Bartter syndrome. Herein, we discuss the case of an overweight 12.9-year-old girl of short stature presenting with hypokalemic metabolic alkalosis. The patient, on the basis of detection of a heterozygous mutation in the SLC12A3 gene and poor growth hormone (GH) responses in two provocative tests, was diagnosed with Gitelman syndrome combined with complete GH deficiency. GH treatment accompanied by magnesium oxide and potassium replacement was associated with a good clinical response.
Abdominal Pain ; Alkalosis ; Bartter Syndrome ; Diarrhea ; Gitelman Syndrome ; Growth Hormone ; Humans ; Incidence ; Kidney ; Magnesium Oxide ; Muscle Cramp ; Muscle Weakness ; Overweight ; Potassium ; Sodium Chloride Symporters ; Tetany ; Vomiting