Eight-year trajectories and predictors of cognitive function in community-dwelling Korean older adults with cardiovascular diseases.

PURPOSE: This study aims to identify longitudinal patterns and predictors of cognitive function trajectories among Korean older adults with cardiovascular diseases. DESIGN: This study is a longitudinal panel analysis based on secondary data. Data from the the Korean Longitudinal Study of Ageing (KLoSA) were used for analysis. METHODS: The KLoSA is a representative panel survey of older Koreans. We analyzed responses from 301 participants aged ≥65 years who completed the same survey more than three times out of five waves between 2012 and 2020. FINDINGS: Latent class growth modeling identified two trajectories of cognitive function in older people with cardiovascular diseases: "low and declining" (n = 81, 26.9%) and "high and declining" (n = 220, 73.1%). Participants in "the low and declining trajectory group" were more likely to have a low educational level, weak handgrip strength, depression, and low social participation at baseline than those in "the high and declining trajectory group." CONCLUSIONS: Our results indicate a need to develop community-based tailored interventions for improving handgrip strength, mental health, and social participation in delaying cognitive decline in older people with cardiovascular diseases considering their educational level. CLINICAL RELEVANCE: Healthcare providers should be more concerned about older people with a weaker handgrip, depression, and low social activities as a high-risk group for cognitive decline over time in cardiovascular care. Therefore, it is necessary to evaluate them early with standardized tools and make subsequent strategies for the older population with cardiovascular diseases.

Rapid and simple isolation and detection of exosomes using CaTiO3:Eu3+@Fe3O4 multifunctional nanocomposites.

Exosomes are potential biomarkers for disease diagnosis and treatment, as well as drug carriers. However, as their isolation and detection remain critical issues, convenient, rapid, low-cost, and effective methods are necessary. In this study, we present a rapid and simple method for directly capturing and analyzing exosomes from complex cell culture media using CaTiO3:Eu3+@Fe3O4 multifunctional nanocomposites. The CaTiO3:Eu3+@Fe3O4 nanocomposites were prepared by high-energy ball-milling and used to isolate exosomes by binding CaTiO3:Eu3+@Fe3O4 nanocomposites and the hydrophilic phosphate head of the exosome phospholipids. Notably, the developed CaTiO3:Eu3+@Fe3O4 multifunctional nanocomposites achieved results comparable with those of commercially available TiO2 and were separated using a magnet within 10 min. Moreover, we report a surface-enhanced Raman scattering (SERS)-based immunoassay for detecting the exosome biomarker CD81. Gold nanorods (Au NRs) were modified with detection antibodies, and antibody-conjugated Au NRs were labeled with 3, 3, diethylthiatricarbocyanine iodide (DTTC) as the SERS tags. A method combining magnetic separation and SERS was developed to detect exosomal biomarker CD81. The results of this study demonstrate the feasibility of this new technique as a useful tool for exosome isolation and detection.

In Addition to Stigma: Cognitive and Autism-Related Predictors of Mental Health in Transgender Adolescents.

OBJECTIVE: Autism spectrum disorder (ASD) is significantly over-represented among transgender adolescents. Independently, ASD and gender diversity are associated with increased mental health risks. Yet, mental health in autistic-transgender adolescents is poorly understood. This study investigates mental health in the largest matched sample to date of autistic-transgender, non-autistic (allistic) transgender, and autistic-cisgender adolescents diagnosed using gold-standard ASD diagnostic procedures. In accordance with advancing understanding of sex/gender-related autism phenotypes, slightly subthreshold autistic diagnostic presentations (common in autistic girls/women) are modeled. METHOD: This study includes 93 adolescents aged 13-21, evenly divided between autistic-transgender, autistic-cisgender, and allistic-transgender groups; 13 transgender adolescents were at the margin of ASD diagnosis and included within a larger "broad-ASD" grouping. Psychological and neuropsychological evaluation included assessment of mental health, IQ, LGBT stigma, ASD-related social symptoms, executive functioning (EF), and EF-related barriers to achieving gender-related needs. RESULTS: Autistic-transgender adolescents experienced significantly greater internalizing symptoms compared to allistic-transgender and autistic-cisgender groups. In addition to stigma-related associations with mental health, ASD-related cognitive/neurodevelopmental factors (i.e., poorer EF and greater social symptoms) were associated with worse mental health: specifically, social symptoms and EF gender barriers with greater internalizing and EF problems and EF gender barriers with greater suicidality. Comparing across all ASD and gender-related groups, female gender identity was associated with greater suicidality. CONCLUSIONS: Parsing the heterogeneity of mental health risks among transgender youth is critical for developing targeted assessments and interventions. This study identifies ASD diagnosis, ASD phenotypic characteristics, and EF-related gender barriers as potential risks for poorer mental health in transgender adolescents.

Longitudinal patterns and predictors of self-care behavior trajectories among Korean patients with heart failure: A 6-month prospective study.

PURPOSE: This study aimed to identify distinct trajectories of self-care behaviors over 6 months after hospital discharge in patients with heart failure, including the baseline predictors affecting these trajectories. DESIGN: This was a prospective longitudinal observational cohort study with a 6-month follow-up. METHODS: A total of 158 patients with heart failure (mean age = 66.75 years, 62.7% men) were included in this study. Patients' characteristics, including cognitive function, health literacy, and social support were collected as possible baseline predictors of self-care behavior trajectories using a structured questionnaire and an electronic medical record review. Self-care behaviors were evaluated using the Korean version of the nine-item European Heart Failure Self-care Behavior Scale at baseline, 1, 3, and 6 months after hospital discharge. Latent growth model analysis was conducted to identify the homogeneous subgroups with distinct trajectories of self-care behaviors. Subsequently, multinomial logistic regression was used to assess whether baseline predictors were associated with these trajectories in patients with heart failure. RESULTS: Three distinct self-care behavior trajectory groups were identified: "low-decreased" (n = 33, 20.9%), "middle-increased" (n = 93, 58.9%), and "high-sustained" (n = 32, 20.2%). The multinomial logistic regression analysis showed that baseline adequate health literacy and positive social support significantly predicted patients' belonging to both the middle-increased and high-sustained self-care behavior trajectory groups compared to the low-decreased group. Importantly, better cognitive function at baseline was only significantly associated with the high-sustained self-care behavior trajectory compared to the low-decreased trajectory. CONCLUSION: Our study revealed that only one-fifth of the patients belonged to the high-sustained self-care behavior group 6 months after hospital discharge. Strategies aimed at improving cognitive function, health literacy, and social support should be developed to sustain satisfactory self-care behaviors in patients with heart failure. Further studies with long-term follow-ups are required to identify other possible factors, as well as the baseline predictors of this study affecting longitudinal trajectories of self-care behaviors. CLINICAL RELEVANCE: Healthcare providers should recognize and evaluate the distinct patterns of self-care behaviors over time in patients with heart failure. Importantly, assessing baseline cognitive function, health literacy, and social support before hospital discharge may be necessary to prevent a decline in self-care behaviors over time.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

CoMnO2-Decorated Polyimide-Based Carbon Fiber Electrodes for Wire-Type Asymmetric Supercapacitor Applications.

In this work, we report the carbon fiber-based wire-type asymmetric supercapacitors (ASCs). The highly conductive carbon fibers were prepared by the carbonized and graphitized process using the polyimide (PI) as a carbon fiber precursor. To assemble the ASC device, the CoMnO2-coated and Fe2O3-coated carbon fibers were used as the cathode and the anode materials, respectively. Herein, the nanostructured CoMnO2 were directly deposited onto carbon fibers by a chemical oxidation route without high temperature treatment in presence of ammonium persulfate (APS) as an oxidizing agent. FE-SEM analysis confirmed that the CoMnO2-coated carbon fiber electrode exhibited the porous hierarchical interconnected nanosheet structures, depending on the added amount of APS, and Fe2O3-coated carbon fiber electrode showed a uniform distribution of porous Fe2O3 nanorods over the surface of carbon fibers. The electrochemical properties of the CoMnO2-coated carbon fiber with the concentration of 6 mmol APS presented the enhanced electrochemical activity, probably due to its porous morphologies and good conductivity. Further, to reduce the interfacial contact resistance as well as improve the adhesion between transition metal nanostructures and carbon fibers, the carbon fibers were pre-coated with the Ni layer as a seed layer using an electrochemical deposition method. The fabricated ASC device delivered a specific capacitance of 221 F g-1 at 0.7 A g-1 and good rate capability of 34.8% at 4.9 A g-1. Moreover, the wire-type device displayed the superior energy density of 60.2 Wh kg-1 at a power density of 490 W kg-1 and excellent capacitance retention of 95% up to 3000 charge/discharge cycles.

African Swine Fever Virus in Pork Brought into South Korea by Travelers from China, August 2018.

We tested samples of pork products confiscated from travelers to South Korea for African swine fever virus (ASFV). We detected ASFV in 4 food items confiscated from travelers from Shenyang, China, in August 2018. Surveillance of pork products at country entry points is needed to mitigate the risk for ASFV introduction.

Ruegeria lutea sp. nov., isolated from marine sediment, Masan Bay, South Korea.

A Gram-stain-negative, non-motile, mesophilic, short rod-shaped, aerobic bacterium designated as 318-1T was isolated from a marine sediment collected from Masan Bay, South Korea. Strain 318-1T grew optimally at pH 6-7, at 30 °C and in the presence of 2-3 % (w/v) NaCl, tolerant of up to 8 % (w/v) NaCl, and accumulated poly-ß-hydroxybutyrate (PHB). A comparative analysis of 16S rRNA gene sequences revealed that strain 318-1T formed a distinct phyletic lineage in the genus Ruegeria (family Rhodobacteraceae, class Alphaproteobacteria) and showed high sequence similarity to Ruegeria halocynthiae DSM 27839T (96.5 %) and Shimia haliotis DSM 28453T (96.3 %). Comparing the genome sequence of 318-1T with those of the type strains of seven species of the genus Rugeria and two species of the genus Shimia, the values obtained were below the thresholds with analysis of average nucleotide identities (ANI, 71.6-76.8 %) and in silico DNA-DNA hybridisation, Genome-to-Genome Distance Calculator (GGDC, 18.5-20.6 %). The DNA G+C content was 65.75 mol%. Chemotaxonomic data [predominant quinone ubiquinone Q10; polar lipid profile consisting of major compounds phosphatidylcholine (PC), phosphatidylglycerol (PG), an unidentified aminolipid and an unidentified lipid; major fatty acids summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c)] supported the affiliation of strain 318-1T to the genus Ruegeria. Genomic, chemotaxonomic, and phenotypic differentiation of strain 318-1T from the members of the genus Ruegeria support it as a novel species. On the basis of the results in this study, a novel species, Ruegeria lutea sp. nov., is proposed. The type strain is 318-1T (=JCM 30927T=KEMB 7306-525T=KCTC 72105T).

Enhanced Electron Transfer Mediated by Conjugated Polyelectrolyte and Its Application to Washing-Free DNA Detection.

Direct electron transfer between a redox label and an electrode requires a short working distance (<1-2 nm), and in general an affinity biosensor based on direct electron transfer requires a finely smoothed Au electrode to support efficient target binding. Here we report that direct electron transfer over a longer working distance is possible between (i) an anionic π-conjugated polyelectrolyte (CPE) label having many redox-active sites and (ii) a readily prepared, thin polymeric monolayer-modified indium-tin oxide electrode. In addition, the long CPE label (∼18 nm for 10 kDa) can approach the electrode within the working distance after sandwich-type target-specific binding, and fast CPE-mediated oxidation of ammonia borane along the entire CPE backbone affords high signal amplification.

Child-centered home service design for a family robot companion.

The home robot-based child activity service aims to cultivate children's social emotions. A design theme was produced by interviewing child development experts and parents. The activity service is composed of 50 plays and 70 conversations. These were developed based on activities from psychomotor therapy and the guidelines of Ministry of Early Childhood Education in South Korea. In the field test, 50 children aged five-seven years participated to experience the activity services at home for 4 days. After completing the 4 days of field testing, we conducted customer satisfaction (CSAT) surveys, Godspeed evaluations and interviews to quantitatively and qualitatively verify the evaluations by the children and parents. As a result, 92% of the children and 80% of the parents evaluated that they were satisfied with the service. In addition, our results revealed that the social robot-based service contributed to improving the relationship between children and families by functioning as a messenger. Finally, the lessons learned from the service development and field tests were discussed to aid service designers and robotics engineers.

Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey.

OBJECTIVE: To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. METHODS: The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. RESULTS: Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. CONCLUSION: Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Sesamolin suppresses adipocyte differentiation through Keap1-dependent Nrf2 activation in adipocytes.

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

SARS-CoV-2 antigenemia and RNAemia in association with disease severity in patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Disease Course of Korean African Swine Fever Virus in Domestic Pigs Exposed Intraorally, Intranasally, Intramuscularly, and by Direct Contact with Infected Pigs.

African swine fever (ASF) is a fatal contagious disease affecting swine. The first Korean ASF virus (ASFV) isolate (Korea/Pig/Paju1/2019) was used to compare the disease course of ASFV in pigs inoculated via the four routes. In the challenge experiment, domestic pigs were infected via the intraoral (IO) and intranasal (IN) routes with a 106 50% hemadsorbing dose (HAD50) and an intramuscular (IM) injection of 103 HAD50. In the direct contact (DC) group, five naïve pigs were brought into direct contact with two IM-ASFV-infected pigs. IO-, IN-, and IM-inoculated pigs showed similar disease courses, whereas DC pigs had comparable ASF syndrome after a 7-day latent period. The disease course in the DC route, one of the most common routes of infection, was not significantly different from that in the IO and IN routes. IM and DC groups differed in terms of the severity of fever and hemorrhagic lesions in the lymph nodes and spleen, indicating that the IM route, suitable for early vaccine development trials, is not appropriate for studying the ASFV infection mechanism, including early stage of infection, and IO and IN challenges with a designated dose can be alternatives in trials for assessing ASFV pathogenicity and vaccine efficacy investigations.

Risk Factors for Impaired Cellular or Humoral Immunity after Three Doses of SARS-CoV-2 Vaccine in Healthy and Immunocompromised Individuals.

Background: We aimed to identify the risk factors for impaired cellular and humoral immunity after three doses of the SARS-CoV-2 vaccine. Methods: Six months after the third vaccine dose, T-cell immunity was evaluated using interferon-gamma release assays (IGRAs) in 60 healthy and 139 immunocompromised (IC) individuals, including patients with hematologic malignancy (HM), solid malignancy (SM), rheumatic disease (RD), and kidney transplantation (KT). Neutralizing antibody titers were measured using the plaque reduction neutralization test (PRNT) and surrogate virus neutralization test (sVNT). Results: T-cell immunity results showed that the percentages of IGRA-positive results using wild-type/alpha spike protein (SP) and beta/gamma SP were 85% (51/60) and 75% (45/60), respectively, in healthy individuals and 45.6% (62/136) and 40.4% (55/136), respectively, in IC individuals. IC with SM or KT showed a high percentage of IGRA-negative results. The underlying disease poses a risk for impaired cellular immune response to wild-type SP. The risk was low when all doses were administered as mRNA vaccines. The risk factors for an impaired cellular immune response to beta/gamma SP were underlying disease and monocyte%. In the sVNT using wild-type SP, 12 of 191 (6.3%) individuals tested negative. In the PRNT of 46 random samples, 6 (13%) individuals tested negative for the wild-type virus, and 19 (41.3%) tested negative with omicrons. KT poses a risk for an impaired humoral immune response. Conclusions: Underlying disease poses a risk for impaired cellular immune response after the third dose of the SARS-CoV-2 vaccine; KT poses a risk for impaired humoral immune response, emphasizing the requirement of precautions in patients.

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation.

Foxp3 is a key transcription factor for differentiation and function of regulatory T (Treg) cells that is critical for maintaining immunological self-tolerance. Therefore, increasing Treg function by Foxp3 transduction to regulate an inflammatory immune response is an important goal for the treatment of autoimmune and allergic diseases. Here we have generated a cell-permeable Foxp3 protein by fusion with the unique human HHph-1-PTD (protein transduction domain), examined its regulatory function in T cells, and characterized its therapeutic effect in autoimmune and allergic disease models. HHph-1-Foxp3 was rapidly and effectively transduced into cells within 30 min and conferred suppressor function to CD4(+)CD25(-) T cells as well as directly inhibiting T-cell activation and proliferation. Systemic delivery of HHph-1 Foxp3 remarkably inhibited the autoimmune symptoms of scurfy mice and the development of colitis induced by scurfy or wild-type CD4 T cells. Moreover, intranasal delivery of HHph-1-Foxp3 strongly suppressed ovalbumin-induced allergic airway inflammation. These results demonstrate the clinical potential of the cell-permeable recombinant HHph-1-Foxp3 protein in autoimmune and hypersensitive allergic diseases.

Performance of Reinforced Concrete Beams Strengthened by Bidirectional Carbon-Fiber-Reinforced Polymers Based on Numerical Models.

The use of carbon-fiber-reinforced polymers (CFRPs) for the repair and rehabilitation of reinforced concrete (RC) structures has been receiving a lot of attention. Specifically, the shear strengthening of RC members based on CFRP materials has been treated as an effective and efficient strengthening method. Previous research projects focused on the shear strengthening of RC members with unidirectional CFRP strips. Although the effectiveness of a bidirectional CFRP layout compared to a unidirectional CFRP layout was discussed in several studies, these studies only investigated the issue based on experiments. Morever, the parameters of the bidirectional CFRP layout were not clearly defined. This study investigates the performance of RC beams strengthened by bidirectional CFRP based on numerical models. A numerical model based on finite element analysis is designed. Using the numerical model, the parameters of the horizontal CFRP strips, such as the layouts of horizontal CFRP strips and the number of horizontal CFRP strips, are studied. The results show that the effect of horizontal CFRP strips is maximized if the strips are distributed along the depth. In contrast, the number of horizontal CFRP strips does not significantly affect the shear strength of RC members.

Diagnostic Sensitivity of Saliva and Other Respiratory Tract Samples of SARS-CoV-2 Variants in Patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Contrasting studies on the omicron variant have demonstrated higher viral loads in different clinical specimens, which is consistent with its high transmissibility. We investigated the viral load in clinical specimens that were infected with the SARS-CoV-2 wild-type, delta, and omicron variants, and we analyzed the diagnostic accuracy of upper and lower respiratory specimens for these variants. We performed nested reverse transcription (RT)-polymerase chain reaction (PCR), targeting the spike gene and sequencing for variant classification. RT-PCR was performed using upper and lower respiratory specimens, including saliva from 78 COVID-19 patients (wild-type, delta, and omicron variants). A comparison of the sensitivity and specificity, using the area under the receiver operating characteristic curve (AUC) values from the N gene, showed that the omicron variant saliva samples had a higher sensitivity (AUC = 1.000) than did the delta (AUC = 0.875) and the wild-type (AUC = 0.878) variant samples. The sensitivity of the omicron saliva samples was greater than that of the wild-type nasopharynx and sputum samples (P < 0.001). The viral loads of the saliva samples containing the wild-type, delta, and omicron variants were 8.18 × 105, 2.77 × 106, and 5.69 × 105, respectively, which did not differ significantly (P = 0.610). Statistically significant differences were not observed in the saliva viral loads between vaccinated and nonvaccinated patients who were infected with the omicron variant (P = 0.120). In conclusion, omicron saliva samples had higher sensitivity than did wild-type and delta samples, and the viral load did not significantly differ between vaccinated and nonvaccinated patients. Further research is necessary to elucidate the mechanisms underlying the sensitivity differences. IMPORTANCE Owing to the vast heterogeneity of the studies focused on the correlation between the SARS-CoV-2 omicron variant and COVID-19, accurate comparisons of the specificity and sensitivity of samples and associated outcomes are still inconclusive. Moreover, limited information is available on the leading causes of infection and the factors that are associated with the conditions that underlie the spread of infection. Although several studies have contributed important knowledge regarding infectious specimens, the impact of saliva samples remains unknown. This study showed that the sensitivity of the omicron variant saliva samples was higher than that of the wild-type nasopharyngeal and sputum samples. Moreover, neither vaccinated nor nonvaccinated patients who were infected with the omicron variant showed any significant differences in SARS-CoV-2 viral loads. Hence, this study is an important step toward understanding how saliva sample results are correlated with other specimen results, regardless of the vaccination status of patients who are infected with the SARS-CoV-2 omicron variant.

Activation of Nrf2 by sulfuretin stimulates chondrocyte differentiation and increases bone lengths in zebrafish.

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is a crucial factor in longitudinal bone growth, which is regulated by a complex network of paracrine and endocrine signaling pathways. Here, we show that a phytochemical sulfuretin can stimulate hypertrophic chondrocyte differentiation in vitro and in vivo. We found that sulfuretin stabilized nuclear factor (erythroid-derived 2)-like 2 (Nrf2), stimulated its transcriptional activity, and induced expression of its target genes. Sulfuretin treatment resulted in an increase in body length of zebrafish larvae and induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were significantly abrogated by Nrf2 depletion, suggesting that such stimulatory effects of sulfuretin were dependent on Nrf2, at least in part. Taken together, these data show that sulfuretin has a potential use as supporting ingredients for enhancing bone growth. [BMB Reports 2023; 56(9): 496-501].

Evaluation of humoral immune response in relation to COVID-19 severity over 1 year post-infection: critical cases higher humoral immune response than mild cases.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. We investigated the antibody response against SARS-CoV-2 until 1 year after symptom onset. Methods: We collected 314 serum samples from 97 patients with COVID-19. Antibody responses were tested using an indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT) to detect specific neutralizing antibodies. Results: The positivity rates for neutralizing antibodies at a 1:10 titer cutoff were 58.1% at 1 week, 97.8% at 4 weeks, and 78% at 1 year after symptom onset (53.8% in asymptomatic patients and 89.3% in symptomatic patients). The IFA and anti-S1 ELISA IgG results significantly correlated with neutralizing antibody titers. Critical/fatal cases showed significantly higher antibody titers than the asymptomatic or mild-to-moderate illness groups. Nonetheless, the median number of days to the seroconversion of neutralizing antibodies was 10 and 15 in asymptomatic and symptomatic patients, respectively. The asymptomatic group had a significantly higher neutralizing potency index than the mild-to-severe illness groups. Conclusions: Neutralizing antibodies corresponded to earlier seroconversion but had a shorter presence in the asymptomatic group than in the symptomatic group and were still present 1 year after symptom onset in critical/fatal cases.