Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits

ObjectiveParaplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.MethodsEighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4°C) and fasudil (group 2, n = 6, 4°C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.ResultsTwo days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.ConclusionThese results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.Clinical RelevanceParaplegia or paralysis caused by spinal cord ischemia remains a devastating and unpredictable complication after descending and thoracoabdominal aortic surgery. This study has revealed that fasudil has a neuroprotective effect against ischemic spinal cord injury in rabbits. Inhibition of the Rho/Rho kinase pathway by fasudil reduces the number of infiltrating cells in the ventral horn and prolongs the expression of eNOS. In the near future, Rho kinase may be an important therapeutic target for paraplegia induced by spinal cord ischemia

Results of Hepatitis B Vaccination 3 Years After a Primary Vaccine Series in Medical Students

Objective：To investigate the significance of additional hepatitis B （HB） vaccination in medical students who were unresponsive to a primary vaccine series or those who had lost antibody to hepatitis B surface antigen （anti-HBs）.Methods：Subjects were followed up for 3 years after completion of a primary HB vaccine series. One additional dose was given to those who lost the anti-HBs within 3 years after the initial series, while 3 doses were given to those who had not responded to the initial vaccination. Subjects：100 medical students （59 men and 41 women；mean age on admission to university, 19.4±1.6 years） enrolled at the School of Medicine, Dokkyo Medical University in April 2012.Results：The rate of positivity for anti-HBs was 98％ soon after completion of the primary HB vaccine series and decreased without the need for additional vaccination to 79％, 61％, and 55％ at 1, 2, and 3 years after the primary series, respectively. Eighteen vaccinated subjects （18％） lost the anti-HBs 2 years after the primary series, and all of them responded to 1 additional dose. Another 18 successfully vaccinated subjects （18％） were anti-HBs negative both 1 and 2 years after the primary series；17 of them responded to 1 additional dose. As for 2 subjects （2％） who were unresponsive to the primary series, 1 became anti-HBs-positive for the first time after 3 additional doses given 2 years after the primary series.Conclusion：A number of students became or remained anti-HBs negative after the primary HB vaccination, indicating that its timing and dose of additional vaccination need to be studied further to evaluate its utility

ガクサイテキ ブンヤ ニオケル ガクシ カテイ コウチク オ シヤ ニ イレタ ジュギョウ ヒョウカ アンケート ト ソノ カツヨウ

FD活動は、学士課程において平成20年度から、全ての大学においてその実施が義務化された。 大学教育のなかでも、学際的な学問分野をどの様にして体系化いくかについては課題となっている。 現在授業評価アンケートは、多くの大学で実施されているのが、その内容については大学の教育目標と の関連づけなどに改善の余地がある。本稿では、学際的な分野における授業評価アンケートについて、 ディプローマポリシーに関連する能力達成の項目を導入し、カリキュラム全体のチェックを行うことで、 組織的な評価をおこなう。これを組織的なFD活動に反映させ、学士課程の構築を目指すことの可能性について考察する。Activity for faculty development (FD) was obligated in the course of bachelor in all the university from 2008. An establishment for systematic planning of curriculum for general education and cultural studies in university education. Although class evaluation questionnaires are already employed in most of the univesities，some problems such as lacking the object of education in each university remain to be improved.Qualification of the undergraduate program is required for establishment of the systematic curriculum for various levels or aims of study for students. In the present paper，we discuss on the significance of the reflection of class evaluation questionnaires included the achievement of competences in the class to check the valance of curriculum for evaluation of the university education.We also discuss on the possibility of reflection of the class evaluation questionnaires for the appropriate FD activities that have direction to the qualification of undergraduate program

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Phylogeography of Hynobius yatsui (Amphibia: Caudata) in Kyushu, Japan

The salamander Hynobius yatsui from southwestern Japan was formerly regarded as a small-sized group of H. naevius, but has recently been resurrected as a distinct species. We investigated the phylogeography of H. yatsui from Kyushu Island using partial sequences of the mitochondrial cytochrome b gene. We detected 49 haplotypes in 181 individuals from 24 localities covering the entire geographic distribution of this species on Kyushu. These haplotypes were grouped into two lineages, a northern lineage from northern and central regions, and a southern lineage from the southern region; no haplotypes were shared between the lineages. We surmise that the divergence of the two lineages was induced by volcanic activity that started in the Beppu-Shimabara Graben, between the areas occupied by these two lineages. From the results of a nested clade phylogeographical analysis, we surmise that the high intrapopulation genetic variation observed in the non-volcanic Kyushu Mountains was generated by alternation of contiguous range expansion or long-distance dispersal, and isolation. The current distribution and the observed complicated genetic structures of H. yatsui in Kyushu seem to have been affected first by volcanic activities since the late Pliocene, but subsequent climatic oscillations during the Pleistocene may also have some effects, although it is impossible at this time to differentiate the effects of these two factors

Pure Uterine Lipoma with a Combined Mucinous Cystic and Brenner Ovarian Tumor in a Postmenopausal Woman: A Case Report and Review of the Literature

Lipomatous tumors are rare among uterine mesenchymal tumors. Due to their rarity, information on the clinical development and histological origin are lacking. We report a pure uterine lipoma and present a review of the relevant literature. We encountered a 72-year-old postmenopausal woman who was referred to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations revealed degenerative uterine tumors and a left ovarian cystic tumor with a solid portion. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and postoperative histological examination revealed a uterine lipoma and adenomyosis. The cystic portion was a mucinous cystadenoma, and the solid portion was classified as a Brenner tumor. The postoperative course was uneventful, and the patient was discharged and remained well until follow-up. Our observations suggest that imaging examinations are sufficient for the diagnosis of uterine lipomatous tumors. To the best of our knowledge, the coexistence of a pure uterine lipoma and a mucinous Brenner ovarian tumor has not been documented in the existing literature. The histogenesis of uterine lipomas remains unclear. However, our results, and those from the existing literature, indicate that the mesenchymal stem cells surrounding the perivascular tissue may be implicated, because lipomas of the skin are reported to originate from these cells

Cosmetic benefits of astaxanthin on humans subjects

Two human clinical studies were performed. One was an open-label non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day oral supplementation and 2 ml (78.9 μM solution) per day topical application of astaxanthin. Astaxanthin derived from the microalgae, Haematococcus pluvialis showed improvements in skin wrinkle (crow's feet at week-8), age spot size (cheek at week-8), elasticity (crow's feet at week-8), skin texture (cheek at week-4), moisture content of corneocyte layer (cheek in 10 dry skin subjects at week-8) and corneocyte condition (cheek at week-8). It may suggest that astaxanthin derived from H. pluvialis can improve skin condition in all layers such as corneocyte layer, epidermis, basal layer and dermis by combining oral supplementation and topical treatment. Another was a randomized double-blind placebo controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve the skin condition in not only in women but also in men