Background: Reluctance of people to receive recommended vaccines is a growing concern, as distribution of vaccines is considered critical to ending the COVID-19 pandemic. There is little information ...regarding pregnant women’s views toward coronavirus vaccination in Japan. Therefore, we investigated the vaccination rate and reasons for vaccination and vaccine hesitancy among pregnant women in Japan.Methods: We conducted a cross-sectional study involving 1,791 pregnant women using data from the Japan “COVID-19 and Society” Internet Survey, conducted from July to August 2021, and valid response from 1,621 respondents were analyzed. We defined participants with vaccine hesitancy as those who identified with the statement “I do not want to be vaccinated” or “I want to ‘wait and see’ before getting vaccinated.” Multivariate Poisson regression analysis was used to investigate the factors contributing to vaccine hesitancy.Results: The prevalence of vaccination and vaccine hesitancy among pregnant women was 13.4% (n = 217) and 50.9% (n = 825), respectively. The main reasons for hesitancy were concerns about adverse reactions and negative effects on the fetus and breastfeeding. Vaccine hesitancy was significantly associated with the lack of trust in the government (adjusted prevalence ratio, 1.26; 95% confidence interval, 1.03–1.54). Other factors, such as age, educational attainment, and state of emergency declaration, were not associated with vaccine hesitancy.Conclusions: COVID-19 vaccination is not widespread among pregnant women in Japan, although many vaccines have been shown to be safe in pregnancy. Accurate information dissemination and boosting trust in the government may be important to address vaccine hesitancy among pregnant women.
In the search for novel organic compounds, I think it is of paramount importance not to overlook the pursuit of microorganism diversity and the abilities those microorganisms hold as a resource. In ...commemoration of Professor Satoshi Ōmura's Nobel Prize in Physiology or Medicine, I will briefly describe the microorganism that produces avermectin and then discuss how innovating isolation methods and pioneering isolation sources have opened the door to numerous new microorganism resources. Furthermore, as exploratory research of substances views the world from many different angles-from biological activity to a compound's physiochemical properties-it is possible to discover a novel compound from a well-known microorganism. Based on this, I will discuss the future prospects of exploratory research.
Oxidative stress is a well-known inducer of two major neurodegenerative pathways, neuronal cell death and neurite degeneration. We previously reported that reactive oxygen species (ROS) generated by ...NADPH oxidases induces EGFR-dependent phosphorylation and activation of ZNRF1 ubiquitin ligase in neurons, which promotes neuronal cell death and neurite degeneration. While these findings provide a potential therapeutic avenue for neurodegeneration, a deeper understanding of the molecular mechanisms of this pathway have emerged as key points of interest. Here, we show that a NADPH oxidase subunit p47-phox/neutrophil cytosolic factor 1 regulates ZNRF1 activity. Using an in vitro neurite degeneration model, we demonstrate that transection-induced phosphorylation of p47-phox at the 345th serine residue by p38 MAPK serves as an initiating signal to activate ZNRF1. The phosphorylated p47 (pS345) or a phospho-mimetic mutant p47-phox binds directly to ZNRF1 whereas a phosphorylation-resistant mutant p47-phox cannot bind to ZNRF1 and its overexpression in neurites significantly suppresses ZNRF1 activation, AKT ubiquitination, and degeneration after transection, suggesting that pS345 might enhance the EGFR-mediated phosphorylation-dependent activation of ZNRF1. These results suggest that pS345 might represent an important checkpoint to initiate the ZNRF1-mediated neurite degeneration. Our findings provide novel insights into the mechanism of ROS-mediated neurodegeneration.
•An NADPH oxidase subunit p47 regulates ZNRF1 ubiquitin ligase activity.•Phosphorylation of p47 at S345 (pS345) is an essential step for ZNRF1 activation.•pS345 is an important checkpoint to initiate ROS-mediated neurite degeneration.
We aimed to determine whether acute disseminated encephalomyelitis (ADEM) diagnosis in children is delayed, and if so, to identify the clinical risk factors of delayed diagnosis. Standardised data ...were collected from children with ADEM from 2003 to 2020. Overall diagnostic delay (time between symptom onset and ADEM diagnosis), physicians' delay (between the first medical visit and ADEM diagnosis), and patients' delay (between symptom onset and the first medical visit) were analysed. Thirty ADEM patients were identified, including 16 (54%) with neurological deficits at discharge. Overall, physicians', and patients' delays were 9 (interquartile range IQR 6-20.5), 5.5 (IQR 3-14), and 4 (IQR 2-8) days, respectively. Overall delay was significantly associated with physicians' delay, but not with patients' delay. There were 61 misdiagnoses among 25 (83%) patients, while 5 (17%) were diagnosed correctly at the first visit. The misdiagnoses of common respiratory and gastrointestinal infection and aseptic meningitis were associated with overall and/or physicians' delay. Later onset of specific neurological features suggestive of ADEM was associated with all three diagnostic delays. A unique diagnostic odyssey exists in ADEM. Several clinical risk factors were associated with the diagnostic delay.
The regulation of gene expression is a promising therapeutic approach for many intractable diseases. However, its use in clinical applications requires the efficient delivery of nucleic acids to ...target tissues, which is a major challenge. Recently, various delivery systems employing physical energy, such as ultrasound, magnetic force, electric force, and light, have been developed. Ultrasound-mediated delivery has particularly attracted interest due to its safety and low costs. Its delivery effects are also enhanced when combined with microbubbles or nanobubbles that entrap an ultrasound contrast gas. Furthermore, ultrasound-mediated nucleic acid delivery could be performed only in ultrasound exposed areas. In this review, we summarize the ultrasound-mediated nucleic acid systemic delivery system, using microbubbles or nanobubbles, and discuss its possibilities as a therapeutic tool.
In the development of therapeutic approaches for central nervous system diseases, a significant obstacle is efficient drug delivery across the blood–brain barrier owing to its low permeability. ...Various nanocarriers have been developed for brain-targeted drug delivery by modification with specific ligands. We have previously developed polyethylene glycol-modified liposomes (Bubble liposomes BLs) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA or small interfering RNA carriers and US contrast agents. In this study, we attempted to prepare brain-targeting BLs modified with Angiopep-2 (Ang2) peptide (Ang2-BLs). Ang2 is expected to be a useful ligand for the efficient delivery of nanocarriers to the brain. We showed that Ang2-BLs interacted specifically with brain endothelial cells via low-density lipoprotein receptor-related protein-1. We also confirmed that Ang2-BLs could entrap US contrast gas and had US imaging ability as well as unmodified BLs. Furthermore, we demonstrated that Ang2-BLs accumulated in brain tissue after intravascular injection. These results suggested that Ang2-BLs may be a useful tool for brain-targeted delivery and US imaging via systemic administration.
Endophytic actinomycetes associated with plant roots are a relatively untapped source of potential new bioactive compounds. This is becoming increasingly important, as the returns from discovery ...research on soil-dwelling microbes, have been continuously diminishing. We have isolated more than 1000 strains of actinomycetes from plant roots in our search for novel bioactive compounds, identified and assayed their bioactive metabolites, as well as investigated their biosynthetic genes for generating secondary metabolites. This has resulted in the discovery of several interesting compounds. Creation of plant root clone libraries enabled us to confirm that we had, indeed, isolated endophytes. In this paper, we introduce our approach to this promising line of research, incorporating data from other publications, and illustrate the potential that endophytic actinomycetes offer as a new source of novel lead compounds.
Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave irradiation to provide the corresponding products in high ...regioisomeric ratios. The reaction proceeds via single-electron transfer to initiate the formation of an aryl radical, followed by a kinetically favored 5-exo-trig and subsequent ring expansion.
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