Immunogenicity of COVID-19 Vaccination in Patients With End-Stage Renal Disease Undergoing Maintenance Hemodialysis: The Efficacy of a Mix-and-Match Strategy

BackgroundThe objective of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with end-stage renal disease (ESRD) on hemodialysis.MethodsESRD patients at the hemodialysis center of a tertiary-care university-affiliated hospital and healthy employees at the clinical laboratory center were prospectively recruited between March and June 2021. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody analysis, blood samples were collected serially on days 0, 14, 28, and 56 after the first vaccine dose, and on days 7 and 50 after the second dose. Antibodies against the SARS-CoV-2 spike protein were quantified, and SARS-CoV-2 neutralizing antibodies were measured in the serum and plasma.ResultsThirty-one ESRD patients and 55 healthy employees were regularly monitored. Twenty-five (80.6%) ESRD patients on hemodialysis received a mix-and-match strategy with ChAdOx1-BNT162b2 (AZ–Pf group) and six (19.4%) received two doses of ChAdOx1 (AZ–AZ group). ESRD patients on hemodialysis showed lower binding antibody titers and neutralizing antibody activities compared to healthy participants following the first vaccination with ChAdOx1. After the second dose, AZ-Pf group had higher immunogenicity than healthy people on days 7 and 50. The binding antibody titer and neutralizing antibody activities on days 7 and 50 were significantly higher in the AZ–Pf group than in the AZ–AZ group.ConclusionESRD patients on hemodialysis receiving the mix-and-match strategy (ChAdOx1–BNT162b2) have COVID-19 vaccine immunogenicity comparable to healthy individuals receiving two doses of ChAdOx1.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT04871945","term_id":"NCT04871945"}}NCT04871945     

pH and Redox-Dual Sensitive Chitosan Nanoparticles Having Methyl Ester and Disulfide Linkages for Drug Targeting against Cholangiocarcinoma Cells

The aim of this study is to prepare pH- and redox-sensitive nanoparticles for doxorubicin (DOX) delivery against DOX-resistant HuCC-T1 human cholangiocarcinoma (CCA) cells. For this purpose, L-histidine methyl ester (HIS) was attached to chitosan oligosaccharide (COS) via dithiodipropionic acid (abbreviated as ChitoHISss). DOX-incorporated nanoparticles of ChitoHISss conjugates were fabricated by a dialysis procedure. DOX-resistant HuCC-T1 cells were prepared by repetitive exposure of HuCC-T1 cells to DOX. ChitoHISss nanoparticles showed spherical morphology with a small diameter of less than 200 nm. The acid pH and glutathione (GSH) addition induced changes in the size distribution pattern of ChitoHISss nanoparticles from a narrow/monomodal distribution pattern to a wide/multimodal pattern and increased the fluorescence intensity of the nanoparticle solution. These results indicate that a physicochemical transition of nanoparticles can occur in an acidic pH or redox state. The more acidic the pH or the higher the GSH concentration the higher the drug release rate was, indicating that an acidic environment or higher redox states accelerated drug release from ChitoHISss nanoparticles. Whereas free DOX showed decreased anticancer activity at DOX-resistant HuCC-T1 cells, DOX-incorporated ChitoHISss nanoparticles showed dose-dependent anticancer activity. Intracellular delivery of DOX-incorporated ChitoHISss nanoparticles was relatively increased at an acidic pH and in the presence of GSH, indicating that DOX-incorporated ChitoHISss nanoparticles have superior acidic pH- and redox-sensitive behavior. In an in vivo tumor xenograft model, DOX-incorporated ChitoHISss nanoparticles were specifically delivered to tumor tissues and then efficiently inhibited tumor growth. We suggest that ChitoHISss nanoparticles are a promising candidate for treatment of CCA.     

Application of Machine Learning Approaches to Predict Postnatal Growth Failure in Very Low Birth Weight Infants

PurposeThe aims of the study were to develop and evaluate a machine learning model with which to predict postnatal growth failure (PGF) among very low birth weight (VLBW) infants.Materials and MethodsOf 10425 VLBW infants registered in the Korean Neonatal Network between 2013 and 2017, 7954 infants were included. PGF was defined as a decrease in Z score >1.28 at discharge, compared to that at birth. Six metrics [area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score] were obtained at five time points (at birth, 7 days, 14 days, 28 days after birth, and at discharge). Machine learning models were built using four different techniques [extreme gradient boosting (XGB), random forest, support vector machine, and convolutional neural network] to compare against the conventional multiple logistic regression (MLR) model.ResultsThe XGB algorithm showed the best performance with all six metrics across the board. When compared with MLR, XGB showed a significantly higher AUROC (p=0.03) for Day 7, which was the primary performance metric. Using optimal cut-off points, for Day 7, XGB still showed better performances in terms of AUROC (0.74), accuracy (0.68), and F1 score (0.67). AUROC values seemed to increase slightly from birth to 7 days after birth with significance, almost reaching a plateau after 7 days after birth.ConclusionWe have shown the possibility of predicting PGF through machine learning algorithms, especially XGB. Such models may help neonatologists in the early diagnosis of high-risk infants for PGF for early intervention.     

Monthly and seasonal variations in vestibular neuritis

Seasonal variations in vestibular neuritis (VN) could support the etiology of viral infection. However, several recent studies revealed no significant seasonal variations in VN. Further studies are necessary to determine the etiology of VN. We analyzed patients with VN to evaluate monthly and seasonal variations. Patients with VN who visited our otorhinolaryngology department or were referred to our department from the emergency department between March 2014 and February 2019 were included retrospectively in this study. Differences among the months and seasons of VN visits were analyzed. Patients were divided into 2 groups according to sex and age (65 years or older and younger than 65 years). Differences among the months and seasons of VN visits were analyzed between groups. There were no significant differences in monthly and seasonal distributions in 248 patients with VN. There were also no significant differences in monthly and seasonal distributions in male and female patients or in older and younger patients. There were no significant differences in monthly or seasonal distributions of patients with VN. Factors other than viruses, such as vascular ischemia, should also be considered in the incidence of VN, especially in older patients.     

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

PurposeSince diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state.Materials and MethodsThe anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5′-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells.ResultsThe protein levels of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660.ConclusionIn conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.     

Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-��-stimulated HUVECs

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-α exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)κB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFκB transactivation might be partially related to the down-regulation of these mRNAs in TNF-α-stimulated HUVECs.     

Development of the Korean Standardized Antimicrobial Administration Ratio as a Tool for Benchmarking Antimicrobial Use in Each Hospital

BackgroundThe Korea National Antimicrobial Use Analysis System (KONAS), a benchmarking system for antimicrobial use in hospitals, provides Korean Standardized Antimicrobial Administration Ratio (K-SAAR) for benchmarking. This article describes K-SAAR predictive models to enhance the understanding of K-SAAR, an important benchmarking strategy for antimicrobial usage in KONAS.MethodsWe obtained medical insurance claims data for all hospitalized patients aged ≥ 28 days in all secondary and tertiary care hospitals in South Korea (n = 347) from January 2019 to December 2019 from the Health Insurance Review & Assessment Service. Modeling was performed to derive a prediction value for antimicrobial use in each institution, which corresponded to the denominator value for calculating K-SAAR. The prediction values of antimicrobial use were modeled separately for each category, for all inpatients and adult patients (aged ≥ 15 years), using stepwise negative binomial regression.ResultsThe final models for each antimicrobial category were adjusted for different significant risk factors. In the K-SAAR models of all aged patients as well as adult patients, most antimicrobial categories included the number of hospital beds and the number of operations as significant factors, while some antimicrobial categories included mean age for inpatients, hospital type, and the number of patients transferred from other hospitals as significant factors.ConclusionWe developed a model to predict antimicrobial use rates in Korean hospitals, and the model was used as the denominator of the K-SAAR.     

Usefulness of <Superscript>11</Superscript>C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on <Superscript>18</Superscript>F-FDG PET

The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.     

Three-Point Bending Properties of Hybrid Multi-Materials Using Adhesive Bonding Dependent on Strength Difference between Steel and Aluminum

The mechanical behaviors of two multi-materials, DP590 (steel sheet)–A356 (cast aluminum alloy) and SS330 (steel sheet)–A5052 (aluminum sheet), were studied. A structural adhesive was used for the joining of steel and aluminum at adhesion strengths of 10, 22, and 30 MPa. To demonstrate that the three-point bending properties depend on the difference in strength between steel and aluminum and adhesion strength, optical microscopy (OM), scanning electron microscopy (SEM), and finite-element analysis (FEA) were performed. According to the results of the bending tests on both multi-materials under the same stacking conditions, the flexural stress increased with the improvement in the adhesion strength until interface separation or aluminum fracture. At the same adhesion strength, the DP590 (lower)–A356 (upper) and SS330 (upper)–A5052 (lower) configurations exhibited a tendency to decrease in the sudden stress drop due to aluminum fracture and interface separation. The bending results were analyzed through the FEA and the stress distribution as a function of the stacking and adhesion strength was confirmed.     

Olfactory Stimulation with Volatile Aroma Compounds of Basil (Ocimum basilicum L.) Essential Oil and Linalool Ameliorates White Fat Accumulation and Dyslipidemia in Chronically Stressed Rats

We explored the physiological effects of inhaling basil essential oil (BEO) and/or linalool and identified odor-active aroma compounds in BEO using gas chromatography/mass spectrometry (GC–MS) and GC–olfactometry (GC–O). Linalool was identified as the major volatile compound in BEO. Three groups of rats were administered BEO and linalool via inhalation, while rats in the control group were not. Inhalation of BEO for 20 min only reduced the total weight gain (190.67 ± 2.52 g) and increased the forced swimming time (47.33 ± 14.84 s) compared with the control group (219.67 ± 2.08 g, 8.33 ± 5.13 s). Inhalation of BEO for 5 min (392 ± 21 beats/min) only reduced the pulse compared with the control group (420 ± 19 beats/min). Inhalation of linalool only reduced the weight of white adipose tissue (5.75 ± 0.61 g). The levels of stress-related hormones were not significantly different among the groups. The total cholesterol and triglyceride levels decreased after inhalation of BEO for 20 min (by more than −10% and −15%, respectively). Low-density lipoprotein cholesterol levels were lowered (by more than −10%) by the inhalation of BEO and linalool, regardless of the inhalation time. In particular, BEO inhalation for 20 min was associated with the lowest level of low-density lipoprotein cholesterol (53.94 ± 2.72 mg/dL). High-density lipoprotein cholesterol levels increased after inhalation of BEO (by more than +15%). The atherogenic index and cardiac risk factors were suppressed by BEO inhalation. Animals exposed to BEO and linalool had no significant differences in hepatotoxicity. These data suggest that the inhalation of BEO and linalool may ameliorate cardiovascular and lipid dysfunctions. These effects should be explored further for clinical applications.