Soluble Programmed Cell Death Ligand-1 (sPD-L1) Levels in Various Cancer Types and Normal Populations.

BACKGROUND: To date, PD-L1 expression in tumor tissue, assessed by immunohistochemical stain, is clinically applicable as a predictive companion biomarker for PD-1/PD-L1 inhibitor which has been highlighted over the past several years. Before blood-based sPD-L1 enters clinical use, it is critical to establish the reference range. This study was designed to investigate soluble sPD-L1 levels in various cancer patients and normal population. METHODS: For the detection of sPD-L1, 4 cancer groups (hepatocellular carcinoma, lung cancer, bladder cancer, gastric cancer) and healthy volunteers' samples were analyzed using an ELISA kit. Using a receiver operating characteristic curve, optimal sPD-L1 cutoff levels were determined. RESULTS: The mean serum sPD-L1 level of the normal population was 59.97 pg/mL (range; 23.780 - 115.2 pg/mL). In various cancer types, serum sPD-L1 levels ranged from 38.696 pg/mL to 228.77 pg/mL, and cutoff values under AUC ranged from 60.307 pg/mL to 64.371 pg/mL. CONCLUSIONS: sPD-L1 can be used as a screening biomarker in various cancer patients referring to optimal cutoff levels suggested.

Serum copeptin levels at day two after pituitary surgery and ratio to baseline predict postoperative central diabetes insipidus.

PURPOSE: Central diabetes insipidus is a complication that may occur after pituitary surgery and has been difficult to predict. This study aimed to identify the cutoff levels of serum copeptin and its optimal timing for predicting the occurrence of central diabetes insipidus in patients who underwent transsphenoidal surgery. METHODS: This was a prospective observational study of patients who underwent transsphenoidal surgery for pituitary gland or stalk lesions. Copeptin levels were measured before surgery, 1 h after extubation, and on postoperative days 1, 2, 7, and 90. RESULTS: Among 73 patients, 14 (19.2%) and 13 (17.8%) patients developed transient and permanent central diabetes insipidus, respectively. There was no significant difference in copeptin levels before surgery and 1 h after extubation; copeptin levels on postoperative days 1, 2, 7, and 90 were significantly lower in patients with permanent central diabetes insipidus than in those without central diabetes insipidus. Copeptin measurement on postoperative day 2 exhibited the highest performance for predicting permanent central diabetes insipidus among postoperative days 1, 2, and 7 (area under the curve [95% confidence interval] = 0.754 [0.632-0.876]). Serum copeptin level at postoperative day 2(< 3.1 pmol/L) showed a sensitivity of 92.3% and a negative predictive value of 97.1%. The ratio of copeptin at postoperative day 2 to baseline (< 0.94) presented a sensitivity of 84.6% and a negative predictive value of 94.9%. The copeptin levels > 3.4 and 7.5 pmol/L at postoperative day 2 and 7 may have ruled out the occurrence of CDI with a negative predictive value of 100%. CONCLUSION: The copeptin level at postoperative day 2 and its ratio to baseline can predict the occurrence of permanent central diabetes insipidus after pituitary surgery.

Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. METHODS: In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. RESULTS: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). CONCLUSION: There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

Assessment of antiphospholipid antibodies and calprotectin as biomarkers for discriminating mild from severe COVID-19.

BACKGROUND: To explore the association of thrombo-inflammatory biomarkers with severity in coronavirus disease (COVID-19), we measured antiphospholipid antibodies (aPL) and calprotectin in sera of COVID-19 patients. METHODS: Anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I antibodies were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex flow immunoassay (MFIA) in hospitalized COVID-19 patients (N = 105) and healthy controls (N = 38). Anti-phosphatidylserine/prothrombin antibodies, calprotectin, and C-reactive protein (CRP) levels were also measured. We assessed the potential correlation between calprotectin levels and various laboratory parameters that were measured during the hospitalization period. After stratifying COVID-19 patients into two groups by their oxygenation status or acute respiratory distress syndrome presentation, the discriminatory performance of each biomarker was evaluated. RESULTS: A high proportion of COVID-19 patients (29.5%, 31/105) had low aCL IgM titers that were detectable by ELISA but mostly below the detection limit of MFIA. Calprotectin levels in severe groups of COVID-19 were significantly higher than those in non-severe groups, while CRP levels revealed no significant differences. Serum calprotectin levels showed strong to moderate degree of correlation with other routinely used parameters including peak levels of CRP, ferritin, procalcitonin, BUN, and neutrophil-to-lymphocyte ratio, but a negative correlation with minimal lymphocyte count and CD4+ T cells. The discriminatory performance was highest for calprotectin in discriminating severe groups of COVID-19. CONCLUSIONS: Serum calprotectin levels were significantly elevated in severe COVID-19 cases. The prevalence of clinically significant aPL did not differ. The link between calprotectin and inflammatory pathway in COVID-19 may help improve the management and outcomes of COVID-19 patients.

Acoustic performance of dual-electrode electrostatic sound generators based on CVD graphene on polyimide film.

We investigated the acoustic performance of electrostatic sound-generating devices consisting of bi-layer graphene on polyimide film. The total sound pressure level (SPL) of the sound generated from the devices was measured as a function of source frequency by sweeping, and frequency spectra were measured at 1/3 octave band frequencies. The relationship between various operation conditions and total SPL was determined. In addition, the effects of changing voltage level, adding a DC offset, and using two pairs of electrodes were evaluated. It should be noted that two pairs of electrode operations improved sound generation by about 10 dB over all frequency ranges compared with conventional operation. As for the sound-generating capability, total SPL was 70 dBA at 4 kHz when an AC voltage of 100 Vpp was applied with a DC offset of 100 V. Acoustic characteristics differed from other types of graphene-based sound generators, such as graphene thermoacoustic devices and graphene polyvinylidene fluoride devices. The effects of diameter and distance between electrodes were also studied, and we found that diameter greatly influenced the frequency response. We anticipate that the design information provided in this paper, in addition to describing key parameters of electrostatic sound-generating devices, will facilitate the commercial development of electrostatic sound-generating systems.

Identification of novel epitopes from human papillomavirus type 18 E7 that can sensitize PBMCs of multiple HLA class I against human cervical cancer.

BACKGROUND: To identify the novel epitopes from the human papillomavirus type 18 E7 which can sensitize PBMCs of four different major HLA class I A allele. METHODS: Twenty-four synthetic overlapping 15-amino acid peptides were screened by measuring the frequency of CD8+ cytotoxic T lymphocytes (CTLs)-producing interferon-γ (IFN-γ) by using flow cytometry and ELISpot assays and selected peptides were validated for cytolytic activity by using the 51Cr release assay. Truncated peptides in the selected epitopes were tested to determine the important residues using ELISpot and 51Cr release assay. RESULTS: Among 24 peptides, E781-95DDLRAFQQLFLNTLS (#21) and E789-103LFLNTLSFVCPWCAS (#23) induced significantly higher Th 1 response including IFN-γ production and in vitro cytotoxicity of PBMCs of four different HLA-A alleles against cervical cancer cells than that of other peptides and the negative control (no peptide sensitization). In E781-95 (#21), amino acid position 81, 82 (N-terminus) and 92, 94, 95 (C-terminus) for HLA-A*02:02 and 24:02, and 81, 82 (N-terminus) and 92, 95 (C-terminus) for HLA-A*11:01 and 33:03 were important to elicit Th1 response of PBMCS. In E789-103 (#23), residue 100 and103 (C-terminus) were important to elicit the CD8+ CTL response in HLA-A*02:01, 11:01 and 33:03 and 100, 101, and 103 (C-terminus) were important to elicit the CD8+ CTL response in HLA-A*24:02. CONCLUSIONS: E781-95 (#21) and E789-103 (#23) were identified as novel epitopes from HPV18 E7 which could sensitized PBMCs of four different HLA class I (HLA-A*02:01, 24:02, 11:01 and 33:03). These epitopes could be useful for immune monitoring and immunotherapy for HPV 18+ cervical cancer.

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement.

Objectives: Salivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. Methods: Assay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. Results: The diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. Conclusions: This study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

Preoperative Serum Copeptin Can Predict Delayed Hyponatremia after Pituitary Surgery in the Absence of Arginine Vasopressin Deficiency.

BACKGRUOUND: Delayed postoperative hyponatremia (DPH) is the most common cause of readmission after pituitary surgery. In this study, we aimed to evaluate the cutoff values of serum copeptin and determine the optimal timing for copeptin measurement for the prediction of the occurrence of DPH in patients who undergo endoscopic transsphenoidal approach (eTSA) surgery and tumor resection. METHODS: This was a prospective observational study of 73 patients who underwent eTSA surgery for pituitary or stalk lesions. Copeptin levels were measured before surgery, 1 hour after extubation, and on postoperative days 1, 2, 7, and 90. RESULTS: Among 73 patients, 23 patients (31.5%) developed DPH. The baseline ratio of copeptin to serum sodium level showed the highest predictive performance (area under the curve [AUROC], 0.699), and its optimal cutoff to maximize Youden's index was 2.5×10-11, with a sensitivity of 91.3% and negative predictive value of 92.0%. No significant predictors were identified for patients with transient arginine vasopressin (AVP) deficiency. However, for patients without transient AVP deficiency, the copeptin-to-urine osmolarity ratio at baseline demonstrated the highest predictive performance (AUROC, 0.725). An optimal cutoff of 6.5×10-12 maximized Youden's index, with a sensitivity of 92.9% and a negative predictive value of 94.1%. CONCLUSION: The occurrence of DPH can be predicted using baseline copeptin and its ratio with serum sodium or urine osmolarity only in patients without transient AVP deficiency after pituitary surgery.

Exploratory Clinical Trial of a Depression Diagnostic Software That Integrates Stress Biomarkers and Composite Psychometrics.

OBJECTIVE: This study evaluated the clinical effectiveness of Minds.NAVI, a depression screening kit combining psychometric measures and stress hormone biomarkers, in a prospective clinical trial. The objective was to assess its potential as a depression screening tool and investigate the associations between psychological assessments, salivary hormone staging, and depression severity. METHODS: Thirty-five participants with major depressive disorder and 12 healthy controls (HCs) were included. The Minds.NAVI software, utilizing the PROtective and Vulnerable factors battEry Test (PROVE) and salivary cortisol/dehydroepiandrosterone (DHEA) analysis, was employed. The PROVE test is a comprehensive self-report questionnaire that assesses depressive symptoms, suicide risk, attachment style, adverse childhood experiences, mentalization capacity, and resilience. In addition, salivary cortisol and DHEA levels were measured to evaluate the functional stage of the hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: Minds.NAVI exhibited 100% sensitivity, 91.7% specificity, and 97.9% accuracy in distinguishing depression from HCs within an exploratory small group. Salivary stress hormone phases showed changes with depression stage (p=0.030), and the proportion of patients with "adrenal exhaustion stage" was higher in the moderate/severe depression group (p=0.038). Protective/vulnerable factors differed significantly between controls and depressed groups (p<0.001). Cortisol awakening response inversely correlated with depressive symptom severity (r=-0.31, p=0.034). CONCLUSION: This study suggested possible clinical effectiveness of Minds.NAVI, a depression screening tool that integrates psychometric measures and stress hormone biomarkers. The findings support the potential association between depression, chronic stress, and HPA axis hyporesponsiveness.

Vibroacoustic Characteristics of a Specific Patterned Polymer with Graphene for an Electrostatic Speaker.

Graphene/polymer actuators were developed using bilayer graphene and various polymer substrates for use as transparent, flexible, and robust electrostatic speaker units. Additionally, a resonant frequency shift was induced using a polymer substrate on which various micropatterns were transferred to boost bass. The total sound pressure level (SPL) in the graphene/polymer actuator was measured by a sweep, and the frequency of the spectrum was confirmed to be one-third that of the octave band frequency. The change in the vibroacoustic characteristic with changes in Young's modulus and density was studied for the polymers of the same size and thickness. Particularly, the possibility of boosting bass was confirmed by inducing a resonant frequency shift and increasing the total SPL by adding micropatterns on a polymer substrate under the same conditions. The resonance frequency of 523 Hz and the SPL of 54 dBA in flat polymer film became 296 Hz and 69 dBA in a specific pattern, which produced a sound of >15 dB based on the same flat polymer. We expect that the design and information provided herein can provide the key parameters required to change the resonant frequency in small-size devices for the application of graphene/polymer thin-film actuators.

Short-Term Effects of Weight-Loss Meal Replacement Programs with Various Macronutrient Distributions on Gut Microbiome and Metabolic Parameters: A Pilot Study.

It has emerged the gut microbiome is crucially linked to metabolic health and obesity. Macronutrient distribution has been discussed as a key parameter in weight-loss programs, but little is known about its impact on the gut microbiome. We investigated the effects of weight-loss meal replacement programs with different macronutrient ratios on the gut microbiota and metabolic parameters in subjects with overweight and obesity. Three low-calorie meal replacement programs with different ratios of carbohydrates, proteins, and lipids were designed: a balanced diet (Group B, 60:15:30), a high-lipid-low-carbohydrate diet (Group F, 35:20:55), and a protein-enriched diet (Group P, 40:25:35). Sixty overweight or obese participants were provided with the meals twice daily for 3 weeks. In all groups, diet intervention resulted in reduced body weight and BMI. The relative abundance of Bacteroidetes and Firmicutes phyla decreased and increased, respectively, which increased the Firmicutes/Bacteroidetes (F/B) ratio in all subjects, particularly in Groups B and P. Alpha- and beta-diversity were augmented at the phylum level in Group P. In conclusion, short-term interventions with weight-loss meal replacement programs increased butyrate-producing bacteria and the F/B ratio. Moreover, the protein-enriched diet significantly increased alpha- and beta-diversity compared to the balanced diet and the high-lipid-low-carbohydrate diet.

Identification of novel immunogenic human leukocyte antigen-A 2402-binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer.

BACKGROUND: A study was undertaken to identify new immunogenic human leukocyte antigen (HLA)-A 2402-restricted epitopes from human papillomavirus (HPV) type 16 E7 protein for immunotherapy against cervical cancer. METHODS: Synthetic overlapping peptides were screened by measuring the frequency of CD8(+) cytotoxic T lymphocytes (CTLs) producing intracellular interferon-γ (IFN-γ) using flow cytometry and were validated in SiHa cells with a Cr release cytotoxicity assay. In vivo antitumor effects of peptide-sensitized peripheral blood mononuclear cells (PBMCs) and isolated CD8(+) CTLs were evaluated using BALB/c nude mice with SiHa cell xenotransplants. RESULTS: Among 14 overlapping 15-amino acid peptides, E7(61-75) (CDSTLRLCVQSTHVD) and E7(67-81) (LCVQSTHVDIRTLED) induced significantly higher IFN-γ production (P < .05) and showed higher in vitro cytotoxicity against SiHa cells than did cells sensitized with the negative control. To determine the exact HLA-A 2402-restricted epitopes, a total of 25 overlapping 9- or 10-amino acid peptides spanning E7(61-75) and E7(67-81) were synthesized. E7(61-69) (CDSTLRLCV) and E7(67-76) (LCVQSTHVDI) induced significantly greater IFN-γ production as well as increased in vitro cytotoxicity against SiHa cells compared with those of other peptides and the negative control (P < .01), and the antitumor effects of these peptide-sensitized PBMCs were induced by CD8(+) CTLs. E7(61-69) -sensitized and E7(67-76) -sensitized PBMCs and isolated CD8(+) CTLs showed a much greater suppression of tumor growth in vivo compared with that of control groups treated with PBS (P < .01). The authors also confirmed the synergistic antitumor effect of cisplatin followed by E7(67-76) -sensitized PBMCs in vivo. CONCLUSIONS: E7(61-69) and E7(67-76) were identified as novel HPV type 16 E7 epitopes for HLA-A 2402, which could be used for immunotherapy against cervical cancer.

A Retrospective National Study on Colonization Rate and Antimicrobial Susceptibility of Streptococcus agalactiae in Pregnant Korean Women, 2018-2020.

PURPOSE: The prevalence of Group B Streptococcus (GBS) colonization in pregnant Korean women is increasing; however, nationwide studies are lacking. Therefore, we aimed to analyze regional colonization rates and antimicrobial susceptibility for GBS in pregnant Korean women through a nationwide survey. MATERIALS AND METHODS: From January 2018 to December 2020, data from the Seoul Clinical Laboratories on vaginal swab cultures were retrospectively analyzed to detect maternal GBS carriers. Each swab specimen was inoculated onto a 5% blood agar plate and incubated at 35℃-37℃ in a 5% CO2 incubator for 24 h. GBS isolates were identified using a Microflex MALDI Biotyper. Antimicrobial susceptibility tests were performed using the Vitek 2 automated system. RESULTS: The overall nationwide GBS colonization rate in pregnant Korean women was found to be 10.6% (3578/33721). The maternal GBS colonization rates ranged from 10.5%-10.8% over the 3-year study period. The GBS colonization rates by province, in descending order, were as follows: Jeolla-do, 13.2%; Gangwon-do, 12.0%; Chungcheong-do, 11.8%; Gyeonggi-do, 11.3%; Seoul, 10.2%; and Gyeongsang-do, 9.6%. During the study period, the resistance rates against chloramphenicol, levofloxacin, clindamycin, erythromycin, and tetracycline were 2.6%-2.7%, 18.2%-19.6%, 33.4%-35.7%, 35.6%-36.8%, and 50.5%-53.3%, respectively. CONCLUSION: In pregnant Korean women, GBS colonization rates were in the range of 9.6%-13.2%, with Gyeongsang-do being the lowest and Jeolla-do the highest. The resistance rate against clindamycin was high (33.4%-35.7%). GBS colonization rates during pregnancy should be studied nationwide according to the Centers for Disease Control and Prevention-recommended guidelines with periodic antimicrobial resistance monitoring.

Identification of genetic variants related to metabolic syndrome by next-generation sequencing.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of conditions associated with glucose intolerance, hypertension, abdominal obesity, dyslipidemia, and insulin resistance that increase the risk of cardiovascular diseases (CVD) and type 2 diabetes (T2D). Since MetS is known as a complex symptom with a high incidence of genetic factors, it is important to identify genetic variants for each clinical characteristic of MetS. METHODS: We performed targeted next-generation sequencing (NGS) to identify genetic variants related to obesity, blood glucose, triacylglycerol (TG), and high-density lipoprotein (HDL)-cholesterol level, and hypertension in 48 subjects with MetS and in 48 healthy subjects. RESULTS: NGS analysis revealed that 26 of 48 subjects (54.2%) with MetS had putative non-synonymous variants related to the clinical features of MetS. Of the subjects with MetS, 8 (16.7%) had variants in 4 genes (COL6A2, FTO, SPARC, and MTHFR) related to central obesity, 17 (35.4%) had variants in 6 genes (APOB, SLC2A2, LPA, ABCG5, ABCG8, and GCKR) related to hyperglycemia, 3 (6.3%) had variants in 4 genes (APOA1, APOC2, APOA4, and LMF1) related to hypertriglyceridemia, 8 (16.7%) had variants in 4 genes (ABCA1, CETP, SCARB1, and LDLR) related to low HDL-cholesterolemia, and 5 (10.4%) had variants in ADD1 related to hypertension. CONCLUSIONS: Our findings may contribute to broadening the genetic spectrum of risk variants related to the development of MetS.

Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome.

Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.

Prevalence of monoclonal gammopathy of undetermined significance in an elderly urban Korean population.

Research on the epidemiology of monoclonal gammopathy of undetermined significance (MGUS) is limited in Korea. The aim of this study was to determine the prevalence and characteristics of MGUS in an elderly urban Korean population. A random sample of 1118 Korean elders was selected from residents aged 65 years or older living in Seongnam, Korea 1 year from August 2005. We obtained plasma samples remaining after scheduled tests for the Korean Longitudinal Study on Health and Aging. The mean age of the study population was 72 years (range, 65-97 years). To screen for MGUS, immunofixation and free light-chain (FLC) assays were performed. Age-adjusted and gender-adjusted MGUS prevalence rates in 680 responders were estimated as 3.3% [95% confidence interval (CI) = 2.0-4.6%], and the estimated age-adjusted prevalence of MGUS was 4.3% in men (95% CI = 1.9-6.6%) and 2.6% in women (95% CI = 1.0-4.2%). Abnormal FLC ratios were detected in 10% of MGUS cases. Multivariate analysis of 945 participants revealed that significant risk factors for MGUS included advanced age, male sex, hyperproteinemia, increased erythrocyte sedimentation rate, and abnormal FLC ratio. MGUS is less prevalent among elderly Koreans (3.3%) than other races. This is the first study to estimate the prevalence of MGUS in the Korean elderly population. Our findings should be confirmed with additional studies analyzing follow-up samples from 2010.

A nationwide seroprevalence of total antibody to hepatitis A virus from 2005 to 2009: age and area-adjusted prevalence rates.

BACKGROUND/AIMS: Recent outbreak of hepatitis A in Korea is clearly related to the epidemiological shift of hepatitis A virus (HAV). However, nationwide seroprevalence data have been limited. This study estimated the nationwide, age- and area-adjusted anti-HAV prevalence from 2005 to 2009. METHODS: Retrospective analysis of the results of total anti-HAV test in 25,140 cases which were requested by 1,699 medical institutions throughout the nation to Seoul Clinical Laboratory from Jan. 1 2005 to Dec. 31 2009 was performed. The estimated seroprevalence was adjusted by area and age of the standard population based on the 2005 Census data from Korea National Statistical Office. RESULTS: The area-adjusted anti-HAV prevalence in the children younger than 10 years were 33.4% in 2005 and 69.9% in 2009. The most susceptible age groups to HAV infection during the last 5 years were teenagers and the young adults in their age of twenties. The area-adjusted seroprevalence in 2009 were 11.9% in the age group of 20-29 years, 23.4% in the age group of 10-19 years, 48.4% in the age group of 30-39 years. The population in 40-49 years showed geographically different seroprevalence with the lowest rate in Seoul (80%). CONCLUSIONS: The most susceptible age group to HAV infection is 10-29 years, while the young children less than 10 years showed about 70% seropositivity. The changing seroepidemiology should be monitored continuously for the proper vaccination and patient care.

Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus.

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P < 0.001, percentage difference = - 42.2%) and also in the transient CDI group (P = 0.002, - 27.2%). Three months postoperative copeptin level < 1.9 pmol/L under normal serum sodium levels was the optimal cutoff value for diagnosing permanent CDI with an accuracy of 81.8%, while 3-month postoperative copeptin level ≥ 3.5 pmol/L excluded the CDI with a negative predictive value of 100%. Conclusively, 3 months postoperative copeptin levels significantly decreased from preoperative levels in the transient CDI group as well as the permanent CDI group. Three-month postoperative copeptin levels ≥ 3.5 pmol/L under normal serum sodium levels may be diagnostic for excluding postoperative CDI.

Comparative analysis of mutational hotspots in the spike protein of SARS-CoV-2 isolates from different geographic origins.

The spike (S) protein mutations of SARS-CoV-2 are of major concern in terms of viral transmission and pathogenesis. Hence, we developed a PCR-based method to rapidly detect the 6 mutational hotspots (H49Y, G476S, V483A, H519Q, A520S, and D614G) in the S protein and applied this method to analyze the hotspots in the viral isolates from different geographical origins. Here, we identified that there was only the D614G mutation in the viral isolates. As of September 30, 2020, the analysis of 113,381 sequences available from the public repositories revealed that the SARS-CoV-2 variant carrying G614 has become the most prevalent form globally. Our results support recent epidemiological and genomic data demonstrating that the viral infectivity and transmission are enhanced by the S protein D614G mutation.

Novel indel mutation in the N gene of SARS-CoV-2 clinical samples that were diagnosed positive in a commercial RT-PCR assay.

Commercially available reverse transcription-polymerase chain reaction (RT-PCR) kits are being used as an important tool to diagnose SARS-CoV-2 infection in clinical laboratories worldwide. However, some kits lack sufficient clinical evaluation due to the need for emergency use caused by the current COVID-19 pandemic. Here we found that a novel insertion/deletion mutation in the nucleocapsid (N) gene of SARS-CoV-2 samples is a cause of negative results for the N gene in a widely used assay that received emergency use authorization (EUA) from US FDA and Conformite Europeenne-in vitro diagnostics (CE-IVD) from EU. Although SARS-CoV-2 is diagnosed positive by other target probes in the assay, our findings provide an evidence of the genetic variability and rapid evolution of SARS-CoV-2 as well as a reference in designing commercial RT-PCR assays.