Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

AbstractHere, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471) and the in vitro chromosomal aberration test (OECD test guideline No. 473) under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU) was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low

Transcript Annotation in FANTOM3: Mouse Gene Catalog Based on Physical cDNAs

The international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM2, comprised 60,770 full-length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein-coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full-length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web-based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full-length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding (including partial or truncated transcripts), providing to our knowledge the greatest current coverage of the mouse proteome by full-length cDNAs. The total number of distinct non-protein-coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species

島嶼集落における社会的かかわり状況と見守り、防災、医療体制について : 奄美大島大和村における中高年者調査から

本研究の目的は奄美大島大和村における中高年者の社会的かかわり状況、見守り体制、災害への備え、医療体制などの現状と課題をアンケート調査により把握し、地域課題の改善に役立てることである。民生委員の協力を得た留置き調査により、40歳以上の1,240人を調査対象とし、928人から回答を得た（回収率74.8%）。近隣の交流は少し減ってきていた。社会とのかかわりでは女性の方が男性よりも高く、年齢が高くなるにつれ低くなる傾向にあった。自然な形での見守りがなされていたが、高齢になると見守り体制への要求もあった。集落の防災組織がうまく機能しているが、災害弱者や避難などへの対処に課題を残していた。医療体制については診療所への満足がある一方、緊急医療や専門医療への要望が強かった。地域の課題では買い物が不便とかハブの存在など社会的・自然的課題があった。The purpose of the study was to assess the present state of the social interaction, the supporting system, the disaster prevention measures, and the medical system in Yamato Village of Amami Oshima island. A questionnaire was personally delivered to 1240 residents of 40-year-old and above and later picked up by commissioned welfare volunteers. The number of people who responded to the questionnaire was 928 and the rate of collection was 74.8%.Neighborhood interaction decreased a little. Social interaction of women was higher than men. Social interaction of the elderly was lower than the younger. Although there were spontaneous watch activities in a natural way, the elderly hoped to have the local supporting system for them. The voluntary organizations for disaster prevention were well functioned, but there remained challenges of the measures for the vulnerable people and the emergency evacuation. With respect to the medical system, there was satisfaction with the community clinic, but on the other hand, there remained wishes regarding emergency medical system and specialized medical service. There were also social and natural problems that the shopping was inconvenient, and that the poisonous snake harmed people, and so on

島嶼集落高齢者の生きがい感に及ぼす社会関連性の影響

本研究の目的は島嶼集落に居住する高齢者の生きがい感に及ぼす社会関連性の影響を検討することである。鹿児島県の離島にある小規模自治体の高齢者に配票調査を実施し、455人の回答を分析した。生きがい感は「ふつう」レベルであり、年齢が低い方が生きがい感が高い傾向にあった。社会関連性指標の因子分析の結果、安梅（2000）と同じ5因子が見いだされた。社会関連性指標の全体の得点に性差や年齢差は見られなかった。女性の方が男性よりも得点が高いのは｢他者とのかかわり」「生活の安心感」「生活の主体性」であった。前期高齢者の方が後期高齢者よりも得点が高いのは「社会への関心」「身近な社会参加」であり、後期高齢者の方が前期高齢者よりも得点が高いのは「生活の主体性」であった。重回帰分析の結果、男女で共通して生きがい感に影響を及ぼしていた因子は「生活の安心感」「社会への関心」「生活の主体性」であった。性と年齢ともに共通して生きがい感に影響を及ぼしていた因子は「生活の主体性」であった。The purpose of the study was to investigate the effects of the indices of social interaction on the feeling that life is worth living. The questionnaire was personally delivered to the elderly who live in villages of an island in Kagoshima prefecture and picked up by commissioned welfare volunteers. The number of people who responded to the question items was 455. The level of the feeling that life is worth living was moderate, and its average score of the elderly aged 75 or over was lower than those of the young-old. Factor analysis of the social interaction measures resulted in five factors as Anme (2000) found. There was no difference related to gender or age in the total score of social interaction. Females\u27 scores of "Interaction", "Feeling of safety", and "Independence" were higher than those of males. The young-old\u27s scores of "Social curiosity" and "Participation in the society" were higher than those of the elderly aged 75 or over. The old-old\u27s score of "Independence" was higher than that of the young-old. The results of multiple regression analysis showed that for both of men and women, "Feeling of safety", "Social curiosity" and "Independence" were found respectively to affect the degrees of the feeling that life is worth living. For the respondents of both gender and age, "Independence" was relevant to the degrees of feeling that life is worth living

島嶼集落における社会的かかわり状況と見守り、防災、医療体制について : 奄美市住用町における中高年者調査から

本研究の目的は奄美市住用町における中高年者の社会的かかわり状況と、見守り体制、災害への備え、医療体制などの現状と課題をアンケート調査により把握し、地域課題の改善に役立てることである。郵送調査により、５５歳以上74歳以下の476人を調査対象とし、175人から回答を得た（回収率36.8％)。回答者は夫婦世帯が多く、世帯収入は年金が多かった。地域の交流は少し減ってきていたが、地域への愛着は高かった。家族との交流、近所づき合い、相談相手、役割などは女性の方が男性よりも良好であった。見守りは自然な形でなされていたが、見守り体制作りへの要求もあった。集落の防災組織はうまく機能しているが、避難所の確保や水害対策などに課題を残していた。医療体制については診療所への肯定的評価がある一方、緊急医療や専門医療への要望が強かった。地域の課題では買い物が不便とか自然災害に弱いなど社会的・自然的課題があった。The purpose of the study was to assess the present state of the social interaction, the supporting system, the disaster prevention measures, and the medical system in Sumiyo Town of Amami City. A questionnaire was personally mailed to 476 residents of 55 to 74-year-old and later returned. The number of people who responded to the questionnaire was 175 and the rate of collection was 36.8%.The respondents to this survey were mostly couple households and their income was mainly a pension. Neighborhood interaction decreased a little. An attachment to the local community was strong. Social interaction of women (e.g. contact with family member, relations with neighbors, having counsel, and having active role) was stronger than men. Although there were spontaneous watch over activities in a natural way, the respondents hoped to have a supporting system for them. The voluntary organizations for disaster prevention were well functioned, but there were issues of making a safe shelter and establishing flood-control measures. With respect to the medical system, there was a satisfaction with the community clinic, but on the other hand, there remained demands for an emergency medical system and a specialized medical service. There were also social and natural problems that the shopping was inconvenient, the town was prone to natural disasters, and so on

奄美大島と八重山諸島における集落等の現状と課題 : 集落・町内会・自治会代表者へのアンケート調査から

本研究の目的は、琉球弧の島喚集落の現状と課題を明らかにすることであった。奄美大島と八重山諸島の集落・町内会・自治会の代表者を調査対象にした郵送調査を実施し、177人から回答を得た(回収率61.9%)。調査内容は、集落の団体、集落の行事、集落維持の見通し、郷友会、支え合い活動、災害対策の現状、集落の課題、回答者の個人属性等であった。結果、台風被害、伝統的行事の種類、郷友会の現状、支え合い活動については奄美大島と八重山諸島で共通性が見られた。一方、八重山諸島のように観光産業が盛んでない奄美大島では人口減少が大きいため課題を抱えた集落が多かった。また、伝統的行事の存続や集落の維持の見通しについても奄美大島の方がより深刻であった。The purpose of this study was to clarify the actual conditions and problems of the village communities in the islands of the Ryukyu arc. The questionnaire survey was conducted on 286 chiefs of the village communities and the neighborhood associations in Amami Oshima and the Yaeyama islands. The number of respondents was 177, and the response rate was 61.9%. The contents of the questions were concerning the associations in the village community, the present situations and the prospects for the maintenance of the traditional events, "Goyukai" (immigrant\u27s voluntary association), the situations of the reciprocal help activities, the disaster-related measures, the problems of the community, and the personal attributes of the respondents. Amami Oshima and the Yaeyama islands had many common features as to typhoon damage, traditional events, the present state of "Goyukai", and mutual support activities. On the other hand, since Amami Oshima was less active in the tourism industry than the Yaeyama islands, many village communities in Amami Oshima had some problems due to a decrease in population. They were also pessimistic about prospects for the maintenance of the traditional events and the community itself

奄美諸島と八重山諸島における高齢者の生活と福祉ニーズ : 将来の生活の不安と生きがい感、食生活、保健医療・福祉サービス、地域の問題(2)

本研究の目的は、琉球弧の北に位世する鹿児島県の奄美諸励と南に位置する沖縄県の八重山諸島における島嘆地域の高齢者の生活の現状と福祉ニーズを把握することである。調査対象地は、奄美諸島の中心である奄美市(島嶼都市部)および瀬戸内町の加計呂麻島、請島、与路島(島嶼集落部)、八重山諸島の中心である石垣市(島嶼都市部)、竹富町西表島西部および鳩間島(島嶼集落部)であった。鹿児島県の場合、特に島嘆集落は過疎高齢化が進行し、集落機能の低下を余儀なくされている。沖細県の場合、鹿児島県ほどの過疎高齢化は進んでいない状況であるが、島嶼地域のもつ生活上の課題を共有している。いずれも、相互扶助の伝統等の地域文化あるいはその精神が残っているという共通点を持つ地域である。本稿では、前稿に引き続き、日常生活の不安と生きがい感､食生活､保健医療･福祉サービス、暮らし向きと地域の問題等についての分析結果とそのまとめを示す。将来の生活不安は島喚集落部の方が島嶼都市部よりも不安を感じる人が多かった。一方、生きがい感は、島嶼都市部の方が高かった。食生活では、栄養面のバランスを欠きやすい環境下にあった。保健医療では、島嶼集落部は医療サービスの地域格差への不満や問題が見られると同時に、健康に対するセルフケア意識の高さが伺えた。福祉サービスでは、島嶼集落部では天候や交通手段によるサービスの中止や困難性などが生じていた。暮らし向きと地域の問題では地域差はなく、共通して台風､交際費､老後の生活の不安があげられ、特に瀬戸内町で地域の問題を感じている人が多かった。The purpose of the study was to investigate the life styles and the social welfare needs of the　elderly who live on the Amami Islands and the Yaeyama Islands through a questionnaire survey. The regions surveyed were the urban area of the Amami Ohshima (Amami City) and the rural area of the Kakeroma Islands (Setouchi Town) in Kagoshima prefecture, and the urban area of Ishigaki Island (Ishigaki City) and the rural area of Iriomote Island and Hatoma Island (Taketomi Town) in Okinawa Prefecture. The people who dwell on these remote islands are usually under unfavorable conditions geographically and economically and the communities there are under functional decline due to depopulation and aging. On the other hand, these islands keep the spirit of mutual helping and the traditional cultures. In this paper we report analyses of the anxiety about future life, the feeling that life is worth living, the eating habits, the evaluation of health-care services and welfare services, the family finances, and other regional issues. The anxiety about future life was higher in the rural areas of the islands than in the urban areas. On the other hand, the feeling that life is worth living was higher in the urban areas of the islands than in the rural areas. Respondents were prone to eat poor-balanced meals. In the rural areas of the islands, while they expressed their dissatisfaction with regional gaps of health-care services, they showed high awareness of self-care about their own health. In the rural areas of the islands, welfare services at home were sometimes cancelled by bad weather or transportation trouble by sea. There was no difference in the family finances and regional issues between areas. Regional issues shared by all islands were the vulnerability to typhoons, high social expenses, and the anxiety about life in the future, and especially the elderly in the Setouchi Town listed more regional issues than those in other areas.area of the Kakeroma Islands (Setouchi Town) in Kagoshima prefecture, and the urban area of Ishigaki Island (Ishigaki City) and the rural area of Iriomote Island and Hatoma Island (Taketomi Town) in Okinawa Prefecture. The people who dwell on these remote islands are usually under unfavorable conditions geographically and economically and the communities there are underfunctional decline due to depopulation and aging. On the other hand, these islands keep the spirit of mutual helping and the traditional cultures.In this paper we report analyses of the anxiety about future life, the feeling that life is worth living, the eating habits, the evaluation of health-care services and welfare services, the family finances, and other regional issues. The anxiety about future life was higher in the rural areas ofthe islands than in the urban areas. On the other hand, the feeling that life is worth living was higher in the urban areas of the islands than in the rural areas. Respondents were prone to eat poor-balanced meals. In the rural areas of the islands, while they expressed their dissatisfaction with regional gaps of health-care services, they showed high awareness of self-care about their own health. In the rural areas of the islands, welfare services at home were sometimes cancelled by bad weather or transportation trouble by sea. There was no difference in the family finances and regional issues between areas. Regional issues shared by all islands were the vulnerability to typhoons, high social expenses, and the anxiety about life in the future, and especially the elderly in the Setouchi Town listed more regional issues than those in other areas

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

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

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)