Oxaliplatin-Associated Amaurosis Fugax

Oxaliplatin-associated amaurosis fugax has not been reported, and its clinical course and treatment remain largely unclear. A 70-year-old man with advanced gastric cancer was treated with the SOX regimen. After cycle 1 of oxaliplatin infusion, the patient realized that his right eye had visual field impairment, which he described as darkening of the right half of his visual field and loss of vision lasting about 1 min and occurring about 7 times a day. The daily frequency of this occurrence gradually decreased, and his visual field impairment improved in 1 week. However, as the same symptoms recurred from cycle 2 to cycle 5 of treatment, oxaliplatin was discontinued from cycle 6 and switched to S-1 monotherapy. Subsequently, the patient’s amaurosis fugax improved. To our knowledge, this is the first report describing clinical course and treatment of oxaliplatin-associated amaurosis fugax

Validity and reliability of a smartphone application for self-measurement of active shoulder range of motion in a standing position among healthy adults

[Background] Shoulder range of motion (ROM) is one of the most important indicators of shoulder disease severity, function, and physical assessment. A universal goniometer (UG) was used as a gold standard for ROM measurement. Recently, smartphone applications for ROM measurement have attracted attention as alternatives to UG. This study aimed to investigate the validity and reliability of active ROM measurements using a smartphone application goniometer that can be used by patients in a standing position. [Methods] The dominant shoulders of 19 healthy participants were included in the study. The 2 observers who were physical therapists used the UG, whereas the participants used a smartphone application goniometer to measure the shoulder ROM. A recorder, who is a physical therapist independent of the observer and participant, read and recorded the shoulder ROM measurements. The order of the measurement movements and devices used was randomized. [Results] Agreement between the smartphone application goniometer and UG (percentage of participants for whom the difference between the UG and application measurements was within ±20% of the mean of the goniometer and application measurements) ranged between 42% and 100%. The intraclass correlation coefficient values (3, 1) for the agreement between the smartphone application goniometer and UG was between 0.72 and 0.97, showing significant and approximately perfect correlations. [Conclusion] High agreement with the UG showed excellent validity, indicating that the smartphone application goniometer used by the participants in the standing position is an excellent method and instrument. The results suggest a simpler, more reliable, practical, and inexpensive method for measuring ROM required for telerehabilitation

Mix Cropping Trial of Determinate and Indeterminate Soybean Lines in Kawatabi Field Science Center

Poster Session

Hochuekkito (TJ-41), a Kampo Formula, Ameliorates Cachexia Induced by Colon 26 Adenocarcinoma in Mice

Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer

尊厳ある食と排泄ケアを考える啓発活動 : しまね女性ファンド助成事業実施報告

咀嚼や嚥下機能に障害があっても安全に楽しくおいしい食生活が送れるよう、知恵と工夫を出し合う“場”と“情報”と“サービス”を提供していきたいと考え、 3年前に「食べ蔵（たべぞう）の会」を設立し、活動してきた。食の問題だけでなく、同時に尊厳ある排泄ケアにも取り組んでいく必要があると考えるようになった。そこで、学び合い、啓発を目的に、 しまね女性ファンド助成により「豊かに生きる－食べること・出すこと・・・自分らしく－」をテーマに、研修会を企画・実施した。その結果、継続の必要性を実感し、参加者のアンケート結果を元に、今後の活動の方向性を検討した

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

地域在住高齢者の趣味の有無と認知機能の関連

高齢者の趣味の有無が認知機能と関連しているとの報告が多くなされている。今回、地域在住一般高齢者272名（平均年齢72.3歳）を対象に趣味の有無と認知機能の関連を検討した。趣味を有する群（186名）と無趣味群（86名）では、主観的幸福感、抑うつ程度、 日常生活動作には有意差は見られなかったが、認知機能においては、趣味を有する群では無趣味群に比して有意に高値であった。また、趣味を有する群では、無趣味群に比して、物事に好奇心があり、社交的な性格であった。認知症予防において、趣味を持つことを積極的に勧めることは重要と思われる

地域在住高齢者の認知機能とビタミンEの関連

抗酸化ビタミンの１つであるビタミンEと認知機能の関連について検討した。対象は地域在住一般高齢者254名（73.1±5.2歳、男性101名、女性153名）で、認知機能はミニメンタルテスト（MMSE）で測定し、また、MMSE特典の1年間の変化により、改善群（MMSEにて2-6ポイント増加）24名（平均年齢72.9歳）、不変群（1ポイント以内）45名（73.5歳）、悪化群（2-6ポイント減少）25名（73.9歳）の3群に分け検討した。年齢、主観的幸福感、抑うつ程度、日常生活動作と血漿ビタミンE値の間には相関はみられなかったが、MMSEとビタミンE値とは弱いながらも正相関が認められた（p=0.046）。MMSE改善群、不変群、悪化群の血漿ビタミンE値は、それぞれ10.5±2.5μg/mL、11.1±4.3μg/mL、10.5±3.9μg/mLと各群間には有意差は認められなかった。ビタミンEは認知機能の程度とは関連している可能性があるが、認知機能低下の進行とは関連が見られなかった

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care