Spleen stiffness-spleen size-to-platelet ratio risk score as noninvasive predictors of esophageal varices in patients with hepatitis B virus-related cirrhosis

This study was conducted to evaluate the predictive value of spleen stiffness-spleen size-to-platelet ratio risk score (SSPS) as a noninvasive predictor of esophageal varices (EVs) and to compare it with others.In this retrospective study, from April 2017 to October 2018, a total of 65 patients with hepatitis B virus-related cirrhosis who underwent the liver and spleen stiffness (LS, and SS) measurements by 2 dimensional-shear wave elastography and endoscopic evaluation for EVs were enrolled. Liver stiffness-spleen size-to-platelet ratio risk score (LSPS) and SSPS were calculated. The prognostic values were assessed by the area under the receiver operating characteristic curve (AUC).Twenty-six patients had no EV on endoscopy. Among 39 patients who had EVs, 12 patients had high risk EVs. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting EVs were 0.72, 0.77, 0.80, and 0.85, respectively. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting high-risk EVs were 0.55, 0.78, 0.67, and 0.80, respectively. SSPS had the highest specificity, at 96.15%, for predicting EVs.SSPS may be beneficial to exclude from having EVs and it is expected that the frequency of performing endoscopies for screening EVs can be reduced.     

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study

BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated.MethodThis prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs.ResultsFifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10⁶ peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days.ConclusionSingle-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.     

Lower-Income Predicts Increased Smartphone Use and Problematic Behaviors Among Schoolchildren During COVID-19 Related School Modification: A Longitudinal Study

BackgroundAs the coronavirus disease 2019 (COVID-19) has continued for a couple of years, the long-term effects of the pandemic and the subsequent school curriculum modification on the mental health of children and parents need to be investigated. To clarify the changes that can occur during one school year and to predict the risk factors for vulnerable groups, this study identified parameters relative to children’s screen time, their problematic behavior, and parental depression.MethodsA total of 186 participants were analyzed who were parents of elementary schoolchildren in South Korea. These parents were required to complete a web-based questionnaire twice. The questionnaires were conducted in June 2020 and September 2021. Participants’ general demographics including family income, children’s screen time, sleep patterns, problematic behavior, and parental depression were assessed via the parental questionnaire that included various measurement tools.ResultsChildren’s body mass index (BMI) increased significantly in 2021 (18.94 ± 3.75 vs. 18.14 ± 3.30, P < 0.001). Smartphone frequency of use per week (5.35 vs. 4.54, P < 0.001) and screen time per day (3.52 vs. 3.16, P < 0.001) significantly increased during the period of the COVID-19 pandemic. The television screen time (2.88 vs. 3.26, P < 0.001), frequency of viewing (3.77 vs. 4.77, P < 0.001), and children’s problematic behaviors significantly decreased (9.15 vs. 11.85, P < 0.001). A lower income household was a key predictor of increased smartphone frequency (B = 1.840, 95% confidence interval [CI], 0.923–2.757, P < 0.001) and smartphone screen time (B = 1.992, 95% CI, 1.458–2.525, P < 0.001). The results showed that the lower income household (B = 5.624, 95% CI, 2.927–8.320, P < 0.001) and a child’s psychiatric treatment history (B = 7.579, 95% CI, 5.666–9.492, P < 0.001) was the most significant predictor of problematic behaviors of children and parental depression (B = 3.476, 95% CI, 1.628–5.325, P < 0.001; B = 3.138, 95% CI, 1.827–4.450, P < 0.001).ConclusionThis study suggested that children’s smartphone screen time and BMI increased during COVID-19 because of the school curriculum modification following school closures in South Korea. The increased children’s problematic behaviors and parental depression were predicted by lower-income households and the previous psychiatric history of children. These results indicate that multiple social support systems to the vulnerable group are needed during the ongoing pandemic and that a modified school setting is required.     

Objective Interpretation of the Rapid Urease Test for Helicobacter pylori Infection Using Colorimetry

BackgroundThe rapid urease test (RUT) is a major diagnostic tool for detecting Helicobacter pylori infection. This study aimed to establish an objective method for measuring the color changes in the RUT kit to improve the test’s diagnostic accuracy.MethodsA UV-visible spectrophotometer was selected as the colorimeter; experiments were conducted in three stages to objectively identify the color changes in the RUT kit.ResultsFirst, the urea broth solution showed an identifiable color change from yellow to red as the pH increased by 0.2. The largest transmittance difference detected using the UV-visible spectrophotometer was observed at a 590-nm wavelength. Second, the commercialized RUT kit also showed a gradual color change according to the pH change detected using the UV-visible spectrophotometer. Third, 13 cases of negative RUT results with a biopsy specimen and 16 of positive RUT results were collected. The transmittance detected using the UV-visible spectrophotometer showed a clear division between the positive and negative RUT groups; the largest difference was observed at a 559-nm wavelength. The lowest transmittance in the negative RUT group was 64, while the highest in the positive RUT group was 56, at the 559-nm wavelength. The UV-visible spectrophotometry reading showed a consistency of 92.7% compared with that of manual reading.ConclusionA transmittance of 60 at a 559-nm wavelength detected using UV-visible spectrophotometer can be used as a cutoff value for interpreting RUT results; this will help develop an automatic RUT kit reader with a high accuracy.     

β-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating FoxO1-Dependent Signaling in C2C12 Cell and Mice Model

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although β-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of β-sitosterol effect on the catabolic pathway was not well known. β-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. β-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the β-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when β-sitosterol was treated. The muscle loss inhibitory efficacy of β-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. β-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when β-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, β-sitosterol would be a potential treatment agent for aging sarcopenia.     

Deoxyactein Isolated from Cimicifuga racemosa protects osteoblastic MC3T3‐E1 cells against antimycin A‐induced cytotoxicity

Deoxyactein is one of the major constituents isolated from Cimicifuga racemosa. In the present study, we investigated the protective effects of deoxyactein on antimycin A (mitochondrial electron transport inhibitor)‐induced toxicity in osteoblastic MC3T3‐E1 cells. Exposure of MC3T3‐E1 cells to antimycin A caused significant cell viability loss, as well as mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, intracellular calcium ([Ca²⁺]_i) elevation and oxidative stress. Pretreatment with deoxyactein prior to antimycin A exposure significantly reduced antimycin A‐induced cell damage by preventing mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, [Ca²⁺]_i elevation and oxidative stress. Moreover, deoxyactein increased the activation of PI3K (phosphoinositide 3‐kinase), Akt (protein kinase B) and CREB (cAMP‐response element‐binding protein) inhibited by antimycin A. All these data indicate that deoxyactein may reduce or prevent osteoblasts degeneration in osteoporosis or other degenerative disorders. Copyright © 2011 John Wiley & Sons, Ltd.     

Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant Nagase analbuminemic rats

The importance of plasma protein binding of intravenous furosemide in circulating blood for its urinary excretion and hence its diuretic effects in mutant Nagase analbuminemic rats (NARs, an animal model for human familial analbuminemia) was reported. Based on the furosemide report, the diuretic effects of another loop diuretic, torasemide, could be expected in NARs if plasma protein binding of torasemide is considerable in the rats. This was proven by this study. After intravenous administration of torasemide, 10 mg/kg, to NARs, the plasma protein binding of torasemide was 23.3% in the rats due to binding to alpha- and beta-globulins (this value, 23.3%, was greater than only 12% for furosemide), and hence the percentages of intravenous dose of torasemide excreted in 8-h urine as unchanged drug was 14.9% in the rat (this value was considerably greater than only 7% for furosemide). After intravenous administration of torasemide to NARs, the AUC (301 versus 2680 microg/min/ml) was significantly smaller [due to significantly faster both Cl(r) (4.81 versus 0.386 ml/min/kg) and Cl(nr) (28.3 versus 3.33 ml/min/kg)], terminal half-life (18.3 versus 73.5 min) and mean residence time (6.97 versus 61.8 min) were significantly shorter (due to faster Cl, 33.2 versus 3.74 ml/min/kg), and amount of 8-h urinary excretion of unchanged torasemide (446 versus 323 microg, due to increase in intrinsic renal excretion) was significantly greater than those in control rats. The 8-h urine output and 8-h urinary excretions of sodium and chloride were comparable between two groups of rats although the 8-h urinary excretion of torasemide was significantly greater in NARs. This could be explained by the following. The amount of urinary excretion of torasemide was significantly greater in NARs than that in control rats only between 0 and 30 min urine collection. In both groups of rats, the urinary excretion rate of torasemide during 0-30 min reached an upper plateau with respect to urine flow rate as well urinary excretion rates of sodium and chloride. Therefore, the diuretic effects (8-h urine output and 8-h urinary excretions of sodium and chloride) were not significantly different between the two groups of rats.     

A new acylglycosyl sterol from quisqualis fructus

A new acylglycosyl sterol (4) was isolated from the MeOH extract of Quisqualis Fructus together with four known compounds. On the basis of spectroscopic data, their structures were elucidated as clerosterol (1), betulinic acid (2), methylursolate (3), 3-O-[6'-O-(8Z-octadecenoyl)-beta-D-glucopyranosyl]-clerosterol (4) and alpha-xylofuranosyluracil (5).     

Enhanced protection of Ins-1 β cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4

In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 β cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of pβ-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the pβ-SP-Ex-4 transfected cells, compared with the pβ-Ex-4 transfected cells. To identify the β-cell protection effect of pβ-SP-Ex-4 delivery, the Ins-1 β cells were transfected with pβ-SP-Ex-4 or pβ-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the pβ-SP-Ex-4 transfected cells had higher β-cell viability than the pβ-Ex-4 transfected cells under hypoxia. In addition, the pβ-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the pβ-Ex-4 transfected cells. Therefore, PEI25k/pβ-SP-Ex-4 complex may be useful to protect isolated β cells from apoptosis during transplantation.     

Effects of Wollastonite Fiber and Styrene–Butadiene Latex Polymer on the Long-Term Durability of Cement-Based Repair Materials

Concrete structures are constructed in various geographical environments and climates, and frequently fail to fulfill their original functions over time due to issues such as aging and damage. Research on concrete structure repair materials is being conducted to solve these problems. This study evaluated the durability of a repair material composed of ultra-rapid hardening cement, styrene–butadiene (SB) latex polymer, and wollastonite mineral fiber. The performance targets were as follows: compressive strength of 20 MPa at 1 day of age and 45 MPa at 28 days of age, chloride ion charge passed of less than 1000 Coulombs, carbonation depth of 20 mm or less, and resistance to repeated freezing and thawing (relative dynamic modulus of elasticity) of 80% or more. The ultra-rapid hardening cement:silica sand ratio of 1:1.5 was the experimental variable, and the unit weight of each material in the mix proportion was determined to satisfy the flow requirement of 200 ± 5 mm. This flow ensured sufficient fluidity for spraying, which is the most widely used method for applying repair material. Wollastonite mineral fiber and SB latex polymer were added at 3% and 5% of the unit weight of the binder, respectively. The mechanical property of the repair material was evaluated through compressive strength, and durability was evaluated through chloride ion penetration, alkali resistance, resistance to carbonation, water absorption, and repeated freezing and thawing tests. The compressive strength satisfied both target values, regardless of the addition of SB latex polymer and wollastonite mineral fiber. The chloride ion penetration test, which was used as an indicator of durability, showed that mixtures without SB latex and wollastonite mineral fiber were not satisfied the target charge passed of 1000 Coulombs, while mixtures with latex and mineral fiber reached the target value. Notably, the co-addition of latex and wollastonite fiber showed the highest resistance to chloride ion penetration, alkali ion, carbonation, repeated freezing and thawing, and the least absorption. The results confirmed that the durability of the repair material based on ultra-rapid hardening cement was most effectively improved by the co-addition of SB latex polymer and wollastonite mineral fiber.