前立腺癌高線量率組織内照射期間中における経時変化が尿道・直腸線量に及ぼす影響

金沢大学附属病院【研究目的】前立腺癌の放射線療法には3次元外部照射・強度変調放射線治療・高線量率組織内照射・密封小線源永久挿入療法・粒子線治療があり,中でもイリジウム192高線量率組織内照射は,前立腺に対し大量かつ安全に放射線を投与できる方法として有用であり,その治療効果も高いことが知られている.一方,リスク臓器(尿道,直腸など)に隣接するため放射線療法で起こりうる副作用には排尿障害・直腸障害・性機能障害がその可能性として挙げられる.本研究では,排尿障害と直腸障害の指標となる尿道線量および直腸線量が,現在行われている高線量率組織内照射期間中にどの程度変動するか調査し,発生した副作用との関係性を明らかにすることで,前立腺癌に対する高線量率組織内照射の安全性と有用性をより高め,臨床利用することを最終的な目的とする.【研究方法】高線量率組織内照射を複数日にわたって施行した際,刺入されているアプリケーターの移動や刺入に伴う前立腺の浮腫性変化が生じると考えられている.これまでの研究でアプリケーターの尾側への偏位により前立腺尖部側の尿道線量が増加することを報告してきた.今回は,外照射に対し高線量率組織内照射を先行した群,後行した群でアプリケーターの偏位の程度に違いがあるかどうか,治療計画時及び照射直前に撮影したCT画像から3Dワークステーションを使用して検討した.また,評価基準(骨構造,前立腺内石灰化)の違いによる影響も検討した.【研究成果】アプリケーターの尾側への偏位評価では,後行群でわずかに増加傾向を示した.断面内での偏位評価では,先行群でばらつきの大きい結果を示した.外部放射線治療のタイミングがおよぼす影響も否定できないが,今回の検討では有意差はなかった.評価基準の違いによる検討では,石灰化基準を真値とした場合,骨構造を基準とすると平均3.1mm,最大10.2mmアプリケーターの尾側への偏位を過小評価する傾向が見られた.研究課題/領域番号:23933008, 研究期間(年度):2011出典：研究課題「前立腺癌高線量率組織内照射期間中における経時変化が尿道・直腸線量に及ぼす影響」課題番号23933008（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23933008/）を加工して作

Effect of daily setup errors on individual dose distribution in conventional radiotherapy: An initial study

金沢大学医薬保健研究域保健学系Recent linear accelerators can perform cone-beam computed tomography to correct setup errors immediately before dose delivery. We calculated the dose distribution with setup errors acquired from cone-beam computed tomography to determine a more realistic and individual effect of setup errors. The differences in dose distribution were analyzed. The setup errors of three patients who were irradiated in the neck, esophagus, and pelvic area were obtained retrospectively. We found that the maximum dose variances for the three cases were 19.9-35.9%. The maximum dose variance points were relatively far from the isocenter. The volume of the 10% dose difference had widths of 1.3-1.85 cm around the beam edges. The V95 and mean doses at the clinical target volume were mostly unchanged. Doses around the beam edges were more varied than those around the isocenter for every case. The dose on the spinal cord located near the beam edges varied by 5-10% compared with the dose of the radiotherapy plan in two of the cases. We demonstrated the individual dose distributions of the cases affected by daily setup errors for all fractions. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics

コベツ エイヨウ シドウ ニ ジュウジスル カンリ エイヨウシ オ タイショウ トシタ マナビ ナオシ プログラム ノ ケントウ

【目的】病院管理栄養士が「不足していると感じているスキル」や「希望する学び直しプログラム」と、現在各大学で実施されている学び直しプログラムとを比較し、より効果的に個別栄養指導の質を向上させることができる学び直しプログラムを検討すること。【方法】個別栄養指導業務を行っている病院勤務の直営管理栄養士74名(回収率:82.4%、有効回答者数:61名)を対象として、平成23年10月3日～11月15日に実施した選択および自記式のアンケート調査結果を用い、「勤続年数」や「個別栄養指導経験年数」と、「不足していると感じているスキル」の総数や項目とを比較し、解析を行った。また、各大学で行われている学び直しプログラムの状況について、報告書、ホームページ等から調査した。【結果および考察】「不足していると感じているスキル」の総数は、「勤続年数」、「個別栄養指導経験年数」をそれぞれ5年未満群と5年以上群に群分けした場合、5年以上群で有意に低値を示した。不足していると感じているスキルの中で、5年未満群に比べ5年以上群の方が大きく低値を示したスキルは、主にカウンセリングや栄養教育に関するものであった。これらは個別栄養指導を経験することで不足を補いやすいスキルであると考えられる。一方、「運動療法の知識」、「薬の知識」、「論文読解」などの項目においては、両群間に差が認められなかった。これらは、養成施設では学ばないまたは詳しく学ばない、学んだが忘れている、新しい情報を理解できているか不安、科学英語に自信がない等、個別栄養指導を経験するだけでは補いにくいスキルであると考えられる。これらのことから、複数年の個別栄養指導経験を、短期間プログラムで代替でき、かつ、日頃補いきれない知識を充実させることができるような学び直しプログラムの構築が必要であると考えられた。Purpose The present study aimed to investigate registered dietitians\u27 understanding of the problems involved in individual nutritional guidance, and to find ways to improve the effectiveness of their guidance. Methods The subjects were 74 registered dietitians performing individual nutritional guidance work in hospitals(recovery rate: 82.4%, effective number of respondents: 61). We investigated the following using selection and a self administered questionnaire: 1)number of years\u27 work experience; 2)years of experience in individual nutritional guidance; and 3)skills required to give individual nutritional guidance that I lack. We also investigated reports or websites from other universities to determine the current status of the re learning program there. Results The total number of "Skills required to give individual nutritional guidance that I lack" in the "More than 5 years" group was significantly lower than in the "Less than 5 years" group. Particularly, "Skills of counseling" and "Skills of nutritional education" were the most different between the groups. However, no difference between groups was observed in "Knowledge of exercise therapy", "Knowledge of pharmaceutical agents" and "Skills in article reading"

A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser187 of SNAP-25 with Ala using “knock-in” technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Formation of Anodic Films on Mg-Al Alloys in NaOH solutions at Constant Potentials

The formation behavior and corrosion characteristics of anodic oxide films on pure magnesium and on Mg-Al alloys were investigated, focusing on the effects of anodization potential, aluminum content, temperature, and NaOH concentration. Pure magnesium and Mg-Al alloys were anodized for 600 s at 3, 10, 40, and 80 V in NaOH solutions. It was found that the anodic film formed at 3 V had the best corrosion resistance, regardless of temperature, NaOH concentration, or aluminum content. An especially high current density was observed at applied potentials of 3-7 V on anodization in alkaline NaOH solutions. XRD analysis detected Mg(OH) 2 and MgO peaks in the films on the anodized specimens. The relative intensity of the Mg(OH) 2 XRD peaks decreased with increasing applied potential, while those of MgO increased. Mg(OH) 2 was generated by an active dissolution reaction with high current density at the specimen surface. Generation of Mg(OH) 2 increased with increasing temperature, while that of MgO increased with NaOH concentration. Moreover, the current density after anodization for 600 s at a constant potential decreased with increasing aluminum content in Mg-Al alloys