A use-case analysis of Clinical Data Interchange Standards Consortium/Study Data Tabulation Model in academia in an investigator-initiated clinical trial

Submitting data compliant with the Clinical Data Interchange Standards Consortium (CDISC) standards is mandatory for new drug applications (NDAs). The standards set by CDISC are widely adopted in the pharmaceutical business world. Introduction of CDISC standards in academia can be necessary to reduce labor, resolve the shortage of data managers in academia, and gain new knowledge through standardized data accumulation. However, the introduction of CDISC standards has not progressed in communities within the academia that do not apply for NDAs. Therefore, herein, we created study data tabulation model (SDTM)-compliant datasets within the academia, without outsourcing, to reduce costs associated with investigator-initiated clinical trials. First, we input data from paper case report forms (CRFs) into an electronic data capture system with minimal function for paper CRFs, “Ptosh,” which is compatible with SDTM. Then, we developed a generic program to convert data exported from Ptosh into fully SDTM-compliant datasets. The consistency was then verified with an SDTM validator, Pinnacle21 Community V3.0.1 (P21C). This resulted in generation of SDTM datasets, resolving all “Rejects” in P21C, thereby achieving the required quality level. Although Ptosh directly exports data in SDTM format, manual mapping of items on CRFs to SDTM variables prepared in Ptosh is necessary. SDTM mapping requires extensive knowledge and skills, and it was assumed that mapping is challenging for the staff without in-depth knowledge of CDISC standards and datasets. Therefore, for CDISC dissemination in academia, it is crucial to secure the staff, time, and funding to acquire the knowledge.departmental bulletin pape

Study of Early Childhood Education in Ho Chi Minh City

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Calorie restriction alters the mechanisms of radiation-induced mouse thymic lymphomagenesis

Calorie restriction (CR) suppresses not only spontaneous but also chemical- and radiation-induced carcinogenesis. Our previous study revealed that the cancer-preventive effect of CR is tissue dependent and that CR does not effectively prevent the development of thymic lymphoma (TL). We investigated the association between CR and the genomic alterations of resulting TLs to clarify the underlying resistance mechanism. TLs were obtained from previous and new experiments, in which B6C3F1 mice were exposed to radiation at 1 week of age and fed with a CR or standard (non-CR) diet from 7 weeks throughout their lifetimes. All available TLs were used for analysis of genomic DNA. In contrast to the TLs of the non-CR group, those of the CR group displayed suppression of copy-neutral loss of heterozygosity (LOH) involving relevant tumor suppressor genes (Cdkn2a, Ikzf1, Trp53, Pten), an event regarded as cell division–associated. However, CR did not affect interstitial deletions of those genes, which were observed in both groups. In addition, CR affected the mechanism of Ikzf1 inactivation in TLs: the non-CR group exhibited copy-neutral LOH with duplicated inactive alleles, whereas the CR group showed expression of dominant-negative isoforms accompanying a point mutation or an intragenic deletion. These results suggest that, even though CR reduces cell division–related genomic rearrangements by suppressing cell proliferation, tumors arise via diverse carcinogenic pathways including inactivation of tumor suppressors via interstitial deletions and other mutations. These findings provide a molecular basis for improved prevention strategies that overcome the CR resistance of lymphomagenesis

An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/ thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of transGolgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria

大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポート ─ライフコースとケアリング関係の視点からの分析─

本研究の目的は,ライフコースとケアリング関係の視点から,大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポートとの関連を分析し,地域包括ケアの課題を検討することである。東京都A 市B 団地居住高齢者429 名への訪問調査を2011 年5-6 月に実施した(有効N=196 名,有効回答率:46.0%)。主な結果として,1)生活ニーズのある人(全体の1 割弱)の2-4 割に支援者がおらず,有支援者の2 割弱が家事,買い物,ゴミだし,当番の場合に近所の人を担い手としてあげた(複数回答),2)困りごとの相談相手がいない人は2 割弱で,男性の方が女性よりいない割合が高い,3)ロジスティック回帰分析の結果,独居,男性,近隣ネットワークが小さい方が相談者がいない確率が高いことがわかった。独居や男性など既存の社会ネットワークを活用したソーシャルサポートの活用可能性が乏しいグループには適切な支援策が必要であることが示唆された。小規模調査の限界もあるが,団地居住高齢者の多様な社会関係とソーシャルサポートの現状をふまえての地域包括ケアの課題があきらかになった。The purpose of this study is two-fold: 1) to examine the association between social relationships and support for meeting the daily life needs of elderly people in an urban housing complex from the lifecourse and caring-relations perspectives and 2) to discuss the challenges of community comprehensive care. Structured home-visit interviews were conducted among 429 elderly people at Housing Complex B in City A, in the Tokyo Metropolitan area, from May to June, 2011. Valid responses were obtained from 196 persons, for a response rate of 46.0%. The results are as follows: 1) among the elderly who had daily-life needs (less than ten percent of total respondents), twenty percent relied on neighbors for doing housework, shopping, taking out garbage, and performing duties in the housing complex (multiple answer); 2) less than twenty percent of respondents had no one they could turn to for advice regarding their day-to-day difficulties; and 3) as a result of logistic regression analysis, single people, males, and respondents with small networks of neighbors were found to be less likely than couples, females, and those with large networks of neighbors to have anyone to turn to for advice. Our findings indicate thatit is necessary to have an appropriate support system for those who have limited support available in their existing social network (e.g. single people, males). In spite of the limitation of a small sample, we could clarify some of the challenges for community comprehensive care for elderly people by considering the diverse social relations and social support available to them in a housing complex

A foot-care program to facilitate self-care by the elderly: A non-randomized intervention study UMIN000029632 UMIN

金沢大学医薬保健研究域保健学系Objective: We aimed to evaluate a foot-care awareness program designed to improve foot morphology, physical functioning, and fall prevention among the community-dwelling elderly. Eleven independent community-dwelling elderly women (aged 61-83 years) were provided with foot-care advice and shown effective foot-care techniques to perform regularly for 6 months, and compared with a control group of 10 elderly women who did not receive any intervention. Measurements of foot form, functional capacity, subjective foot movement, and physical function were taken at baseline and 6-month follow-up. Results: At follow-up, improvements were seen in the intervention group in foot morphology, subjective foot movement, foot pressure, and balance. In the intervention group, 90% of women had maintained or improved foot form and none of them had fallen during the post-intervention period, compared to the control group where 30% improved foot form (p = 0.0075) and four (40%) of them had fallen. Therefore, a foot-care program may have the potential to prevent falls and improve mobility among the elderly. Trial Registration UMIN-CTR No. UMIN000029632. Date of Registration: October 19, 2017 © 2017 The Author(s)

Paracrine IL-33 Stimulation Enhances Lipopolysaccharide-Mediated Macrophage Activation

BACKGROUND: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation

Activity Report of the KUD Health Sciences Team in Response to the 2024 Noto Peninsula Earthquake

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