Search

Abstract Background The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been followed by many reports of the development and relapse of autoimmune diseases associated with SARS-CoV-2 vaccination. Some of these reports have involved relapse or onset of immunoglobulin A (IgA) nephropathy following SARS-CoV-2 vaccination. Here, we report on a patient with IgA nephropathy who presented with gross hematuria and rapidly progressive glomerulonephritis following SARS-CoV-2 vaccination. Case presentation A 63-year-old male patient with a history of habitual tonsillitis underwent bilateral tonsillectomy. He had a history of alcoholic cirrhosis of the liver and microscopic hematuria and proteinuria were indicated during a health checkup 2 years before hospital admission. He developed hematuria after the SARS-CoV-2 vaccination, which led to rapidly progressive glomerulonephritis, for which he was hospitalized. A renal biopsy led to the diagnosis of IgA nephropathy. Although pulse steroid therapy during his condition resulted in hepatic encephalopathy, three courses combined with mizoribine improved his renal function. Conclusion SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease.

Abstract Insufficient evidence has been accumulated regarding associations of heated tobacco products (HTPs) use with coronavirus infection and severity of coronavirus disease 2019 (COVID-19), an ongoing pandemic. We conducted a cross-sectional study using data from an internet questionnaire administered in February 2022 to 30,130 individuals from the general Japanese population (age range, 16–81 years). Single users of HTPs and dual users of combustible cigarettes and HTPs comprised 5.2% and 7.3% of respondents, and 6.7% and 38.0% of those infected (n = 1117). Approximately 70% of infected dual users experienced severe disease. Single users of HTPs and dual users were more likely to be infected with coronavirus than never-users (adjusted odds ratio [aOR] = 1.65/4.66; 95% confidence interval [CI] 1.26–2.15/3.89–5.58). Regarding severity, former and current tobacco users (former/combustible cigarettes/HTPs: aOR = 1.88/3.17/1.90; 95%CI 1.11–3.19/1.77–5.67/1.01–3.59) were more likely to be administered oxygen than never-users, and dual users required oxygen administration the most (aOR = 4.15, 95%CI 2.70–6.36). Use of HTPs may increase risks of coronavirus infection and severe COVID-19. Our results provide an opportunity to consider the safety of tobacco products use, including HTPs, during the COVID-19 pandemic.

Abstract Background Currently, in Japan, shifting tasks from physician to hospital pharmacist is being developed to reduce physician workload and improve the quality of pharmacotherapy. This study aimed to investigate the effects of pharmacist involvement in the choice of inhaler as the task on the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD). Methods This prospective, single-center, single-arm study included 36 outpatients with newly diagnosed COPD indicating inhaler therapy. Eligible patients were immediately interviewed by pharmacist. Then, pharmacist assessed patient’s inhalation flow rate, physical function to handle an inhaler, comprehension, and value, and finally recommended a personalized inhaler based on originally developed inhaler choice protocol, and pulmonologist prescribed a pharmacist-selected inhaler. The primary endpoint was the improvement in trough forced expiratory volume in 1 s (FEV1) between baseline and week 26. The secondary endpoints were safety, and improvements at week 26 in scores for the COPD Assessment Test (CAT), modified British Medical Research Council Dyspnea Scale (mMRC), and Adherence Starts with Knowledge-20 (ASK-20). Results The pneumonologists completely agreed with the pharmacist-recommended inhaler. Mean FEV1 significantly increased from baseline to week 26 (1.60, SD 0.54 L vs. 1.98, SD 0.56 L; p

Aerosols, including mineral dust, are transported from China and Mongolia to Japan, particularly in spring. It has been recognized that calcium (Ca) carbonate is the main Ca species in aerosols, which reacts with acidic species such as sulfuric and nitric acids at the surface of mineral dust during its long-range transport, related to mitigation of acid depositions. The similar assumption that magnesium (Mg) originally takes the form of carbonate and contributes to the neutralization reaction and buffering effect on the acidity of aerosols has been suggested in various studies. However, few studies have confirmed this process by measuring actual Mg species in aerosols quantitatively. In this study, X-ray absorption near-edge structure (XANES) spectroscopy was employed to determine Mg species in size-fractionated aerosol samples, including mineral dust. The results showed that (i) most Mg in the mineral dust did not take the form of carbonate and its reacted species (e.g., sulfate and nitrate) produced by the neutralization reaction, but (ii) Mg was mainly found as Mg in the octahedral layer in phyllosilicates. Given that the reactivity of such Mg in phyllosilicates is much lower than those in carbonate minerals, the contribution of Mg to the neutralization reactions in the atmosphere must be lower than previously expected.

Fatty liver is strongly associated with the metabolic syndrome characterized by obesity, insulin resistance, and type 2 diabetes, but the genetic basis and functional mechanisms linking fatty liver with the metabolic syndrome are largely unknown. The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from SM/J and A/J strains and is a model for polygenic type 2 diabetes, characterized by moderately impaired glucose tolerance, hyperinsulinemia, and mild obesity. SMXA-5 mice also developed fatty liver, and a high-fat diet markedly worsened this trait, although SM/J and A/J mice are resistant to fatty liver development under a high-fat diet. To dissect loci for fatty liver in the A/J regions of the SMXA-5 genome, we attempted quantitative trait loci (QTLs) analysis in (SM/J×SMXA-5)F2 intercross mice fed a high-fat diet. We mapped a major QTL for relative liver weight and liver lipid content near D12Mit270 on chromosome 12 and designated this QTL Fl1sa. The A/J allele at this locus contributes to the increase in these traits. We confirmed the effect of Fl1sa on lipid accumulation in liver using the A/J-Chr12SM consomic strain, which showed significantly less accumulation than A/J mice. This suggests that the SM/J and A/J strains, neither of which develops fatty liver, possess loci causing fatty liver and that the coexistence of these loci causes fatty liver in SMXA-5 mice.

Considering that iodine is highly volatile and has low solubility in water, it is utilized as an antiseptic in its complex form (iodophor) with a carrier material. Herein, we prepared the polysorbate 80– iodine complex and investigated its properties. In the presence of 0%, 0.01%, 0.1%, and 1% polysorbate, Pseudomonas putida NBRC 100650 growth was inhibited at 75, 75, 50, and 25 ppm iodine, respectively, indicating that high concentrations of polysorbate 80 enhanced the antibacterial activity of iodine. Absorption spectra of the mixtures of polysorbate 80 and iodine were analyzed; we observed that two peaks at 287 and 350 nm, derived from triiodide ions, shifted to the longer wavelength side in the presence of 0.1% and 1% polysorbate 80. Further, when 1% polysorbate 80 was added to the mixture of soluble starch and iodine, the peak around 580 nm arising from the amylose–iodine complex disappeared, indicating that polysorbate 80 captured iodine from the starch–iodine complex. We also found that polysorbate 80 retained iodine for approximately 4 months and prevented its volatilization; moreover, the mixture did not lose its growth inhibitory activity upon storage for approximately 4 months. Collectively, our data indicated that polysorbate 80 firmly retains low concentrations of iodine and that the polysorbate 80–iodine complex can serve as an antiseptic that can be stably stored for a long time. [ABSTRACT FROM AUTHOR]

In this paper we investigate the Stokes geometry of a perturbed tangential system of the Pearcey system to a hyperplane, in particular, the effect of a new kind of virtual turning point of the system that originates from its multiple-characteristic property at a non-hereditary turning point. We also study the activity of Stokes curves of the system by using the exact steepest descent method. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. LY3502970 is a partial agonist, biased toward G protein activation over ß-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective against other class B G protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration. A highresolution structure of LY3502970 in complex with active-state GLP- 1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain (ECD), extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY3502970 and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetesmellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands. [ABSTRACT FROM AUTHOR]

We prepared an apatite/polymer composite material with a fractal surface by transferring the hierarchical rough surface of a plaster replica onto calcium phosphate paste and immersing the paste in a buffer. The rough structure (fractal dimension: 2.3) accelerated the spreading and penetration of a water droplet placed on the surface. This material can be applied in dental implants and texture testers. [ABSTRACT FROM AUTHOR]

Needle-like hydroxyapatites obtained through a hydration reaction process between anhydrous dicalcium phosphate (ADCP) and tetracalcium phosphate (TTCP) were reinforced with wheat starch to form composite blocks, and they showed mechanical properties corresponding to their compositions: mass fraction of calcium phosphate powders/starch solution and starch concentration. A kind of the composite granules was found to be osteoconductive in an in vivo examination with a rat model. [ABSTRACT FROM AUTHOR]

The carbonaceous asteroid Ryugu has been explored by the Hayabusa2 spacecraft to elucidate the actual nature of hydrous asteroids. Laboratory analyses revealed that the samples from Ryugu are comparable to unheated CI carbonaceous chondrites; however, reflectance spectra of Ryugu samples and CIs do not coincide. Here, we demonstrate that Ryugu sample spectra are reproduced by heating Orgueil CI chondrite at 300°C under reducing conditions, which caused dehydration of terrestrial weathering products and reduction of iron in phyllosilicates. Terrestrial weathering of CIs accounts for the spectral differences between Ryugu sample and CIs, which is more severe than space weathering that likely explains those between asteroid Ryugu and the collected samples. Previous assignments of CI chondrite parent bodies, i.e., chemically most primitive objects in the solar system, are based on the spectra of CI chondrites. This study indicates that actual spectra of CI parent bodies are much darker and flatter at ultraviolet to visible wavelengths than the spectra of CI chondrites. [ABSTRACT FROM AUTHOR]