Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

<p>Abstract</p> <p>Background</p> <p>Recently, manufactured nano/microparticles such as fullerenes (C₆₀), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C₆₀, CB and kaolin, an <it>in vitro </it>micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by <it>in vivo </it>assay systems using male C57BL/6J or <it>gpt </it>delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles.</p> <p>Results</p> <p>In <it>in vitro </it>genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C₆₀, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C₆₀and kaolin, increased either or both of <it>gpt </it>and Spi^-mutant frequencies in the lungs of <it>gpt </it>delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the <it>gpt </it>genes. The G:C to C:G transversion was commonly increased by these particle instillations.</p> <p>Conclusion</p> <p>Manufactured nano/microparticles, CB, C₆₀and kaolin, were shown to be genotoxic in <it>in vitro </it>and <it>in vivo </it>assay systems.</p

CTが診断契機となったディスジャーミノーマIA期の再発症例

　ディスジャーミノーマの術後経過観察において、腫瘍マーカーや内診による身体診察が推奨される一方、CT検査での全身検索については一定の見解が得られていない。今回、ディスジャーミノーマIA期術後に、CTが診断契機となったディスジャーミノーマIA期の傍大動脈リンパ節への単独再発症例を経験したので報告する。　症例は17歳、未妊。下腹部痛を主訴に来院した。MRIで臍高に達する右卵巣の充実性腫瘍を認めた。血液検査にてLDH、ALP、CA125、β-human chorionic gonadotropin(β-hCG)は高値を示したが、α-fetoprotein(AFP)は正常値であった。ディスジャーミノーマを疑い、右付属器切除および大網切除を施行した。術前のCTおよび腹腔内検索でリンパ節腫大や播種性病変を認めなかったため、リンパ節生検は省略した。術後病理でディスジャーミノーマIA期と診断され、術後化学療法は行わず、1ヵ月間隔で経過観察した。術後いずれの腫瘍マーカーも陰性化し、身体診察でも異常を認めず経過したが、術後6ヵ月で虫垂炎を発症。その際に撮影されたCTで、偶発的に傍大動脈リンパ節腫大を認めた。腹腔鏡下傍大動脈リンパ節摘出および虫垂切除術を施行し、ディスジャーミノーマの傍大動脈リンパ節への遠隔再発と診断された。術後BEP療法を3コース行い、現在再発なく経過している。　リンパ節郭清および術後補助化学療法が省略されたディスジャーミノーマIA期は再発のリスクが高いことを認識し、CT検査を含む厳重な経過観察が必要であることが示唆された。(著者抄録

Innovations in online classes introduced during the COVID-19 pandemic and their educational outcomes in Japan

Abstract Background The novel coronavirus disease (COVID-19) pandemic emerged in Japan in February 2020, forcing the adoption of online education by university medical schools across Japan. The advantages and disadvantages of online education have been studied in Japan; however, the educational outcome of online classes conducted during the COVID-19 pandemic has not been completely evaluated. In this study, we examined the relationship between lecture format (e.g., face-to-face or online) and performance of third-year university students in their organ-specific cardiovascular course examination. Methods This retrospective, nonclinical, and noninterventional comparative educational study included 550 third-year medical students who took a cardiovascular course between April 2018 and May 2022. Cardiovascular coursework was conducted in-person in 2018 and 2019, online in 2020 and 2021, and again in-person in 2022. The course comprised 62 lecture and 2 problem-based learning (PBL) sessions. A quiz was set up in advance on Moodle based on all lectures conducted in 2021 and 2022. A written examination was administered at the end of the course to evaluate the knowledge of students. The student online course evaluation questionnaires were administered in 2020 and 2021. Examination scores and proportion of failures in each year were compared. Results The mean examination scores were significantly higher in 2021 and 2022 than in 2018, 2019, and 2020 (p < 0.05). Univariate and multivariate analyses adjusted for the class type, online quiz, and PBL revealed that only online quiz was significantly associated with better examination results (p < 0.05). A student course evaluation survey indicated that the online format did not interfere with the students’ learning and was beneficial. Conclusions The introduction of online classes into medical education due to the COVID-19 pandemic was as effective as face-to-face classes owing to learning management system and other innovations, such as online quizzes. Online education may confer more benefits when provided in a combination with face-to-face learning after COVID-19 pandemic

Elucidation of a Carotenoid Biosynthesis Gene Cluster Encoding a Novel Enzyme, 2,2′-β-Hydroxylase, from Brevundimonas sp. Strain SD212 and Combinatorial Biosynthesis of New or Rare Xanthophylls

A carotenoid biosynthesis gene cluster mediating the production of 2-hydroxyastaxanthin was isolated from the marine bacterium Brevundimonas sp. strain SD212 by using a common crtI sequence as the probe DNA. A sequence analysis revealed this cluster to contain 12 open reading frames (ORFs), including the 7 known genes, crtW, crtY, crtI, crtB, crtE, idi, and crtZ. The individual ORFs were functionally analyzed by complementation studies using Escherichia coli that accumulated various carotenoid precursors due to the presence of other bacterial crt genes. In addition to functionally identifying the known crt genes, we found that one (ORF11, named crtG) coded for a novel enzyme, carotenoid 2,2′-β-hydroxylase, which showed intriguingly partial homology with animal sterol-C5-desaturase. When this crtG gene was introduced into E. coli accumulating zeaxanthin and canthaxanthin, the resulting transformants produced their 2-hydroxylated and 2,2′-dihydroxylated products which were structurally novel or rare xanthophylls, as determined by their nuclear magnetic resonance and high-performance liquid chromatography/photodiode array detector/atmospheric pressure chemical ionization mass spectrometry spectral data. The new carotenoid produced was suggested to have a strong inhibitory effect on lipid peroxidation