Real-time imaging and analysis of differences in cadmium dynamics in rice cultivars (Oryza sativa) using positron-emitting107Cd tracer

<p>Abstract</p> <p>Background</p> <p>Rice is a major source of dietary intake of cadmium (Cd) for populations that consume rice as a staple food. Understanding how Cd is transported into grains through the whole plant body is necessary for reducing rice Cd concentrations to the lowest levels possible, to reduce the associated health risks. In this study, we have visualized and quantitatively analysed the real-time Cd dynamics from roots to grains in typical rice cultivars that differed in grain Cd concentrations. We used positron-emitting¹⁰⁷Cd tracer and an innovative imaging technique, the positron-emitting tracer imaging system (PETIS). In particular, a new method for direct and real-time visualization of the Cd uptake by the roots in the culture was first realized in this work.</p> <p>Results</p> <p>Imaging and quantitative analyses revealed the different patterns in time-varying curves of Cd amounts in the roots of rice cultivars tested. Three low-Cd accumulating cultivars (<it>japonica </it>type) showed rapid saturation curves, whereas three high-Cd accumulating cultivars (<it>indica </it>type) were characterized by curves with a peak within 30 min after¹⁰⁷Cd supplementation, and a subsequent steep decrease resulting in maintenance of lower Cd concentrations in their roots. This difference in Cd dynamics may be attributable to OsHMA3 transporter protein, which was recently shown to be involved in Cd storage in root vacuoles and not functional in the high-Cd accumulating cultivars. Moreover, the PETIS analyses revealed that the high-Cd accumulating cultivars were characterized by rapid and abundant Cd transfer to the shoots from the roots, a faster transport velocity of Cd to the panicles, and Cd accumulation at high levels in their panicles, passing through the nodal portions of the stems where the highest Cd intensities were observed.</p> <p>Conclusions</p> <p>This is the first successful visualization and quantification of the differences in whole-body Cd transport from the roots to the grains of intact plants within rice cultivars that differ in grain Cd concentrations, by using PETIS, a real-time imaging method.</p

Scoring systems for differentiating gastrointestinal stromal tumors and schwannomas from leiomyomas in the stomach

There is no practical predictive model for the diagnosis of gastrointestinal stromal tumors (GISTs). To establish a practical predictive model for the diagnosis of subepithelial lesions in the stomach, we reviewed patients with GISTs (n = 89), schwannomas (n = 7), and leiomyomas (n = 28). The tumor was more frequently found along the gastric cardia in the leiomyoma group (57.1%) than in the GIST/schwannoma group (2.1%, P < .01). Contrast enhancement (57.3% vs 0%, P < .01) and intra-tumoral necrosis (34.4% vs 0.0%, P < .01) were more frequently observed in the GIST/schwannoma group than in the leiomyoma group. On endoscopic ultrasonography, 58.3% of GISTs/schwannomas showed uneven echogenicity, whereas the echogenicity was uneven in 21.4% of leiomyomas (P < .01). There were no differences between the tumor color and the presence or absence of ulcer formation, tumor bleeding, irregularity of the tumor margin, cystic spaces, and hyperechoic spots between the 2 groups. Based on these results, we developed a 2-step diagnostic algorithm for GISTs/schwannomas. The first step comprises 1 endoscopic feature: a cardiac or non-cardiac location. Tumors with a cardiac location were judged as leiomyomas and those with a non-cardiac location were judged as GISTs/schwannomas, with 96.9% sensitivity and 57.1% specificity for GIST/schwannoma diagnosis. The second step comprises a combination of endoscopic (non-cardiac location), radiologic (positive contrast enhancement and intra-tumoral necrosis), and endosonographic (uneven echogenicity) features for a total of 4 points. We assigned 1 point to each feature. Tumors with scores of 2 to 4 were judged as GISTs/schwannomas, with 81.3% sensitivity and 92.9% specificity for GIST/schwannoma diagnosis. Our predictive model will be a practical guide for the management of gastric subepithelial lesions

Endoscopic findings of gastric neoplasms in familial adenomatous polyposis are associated with the phenotypic variations and grades of dysplasia

Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric neoplasms. However, endoscopic findings have not been sufficiently investigated. We investigated the phenotypic expression of gastric adenoma (low-grade dysplasia) and gastric cancer (high-grade dysplasia or carcinoma) in patients with FAP and clarified their relationships to endoscopic findings. Of 29 patients with FAP who underwent esophagogastroduodenoscopy between 2005 and 2020, 11 (38%) had histologically confirmed gastric neoplasms, including 23 lesions of gastric adenoma and 9 lesions of gastric cancer. The gastric neoplasms were classified into 3 phenotypes (gastric, mixed, or intestinal type) according to the immunostaining results and evaluated for location (U or M region: upper or middle third of the stomach or L region: lower third of the stomach), color (same as the background mucosa, whitish, or reddish), macroscopic type (elevated, flat, or depressed), background mucosal atrophy (present or absent), fundic gland polyps in the surrounding mucosa (present or absent), and morphologic changes in tumor size. Elevated whitish gastric adenomas were further subdivided by macroscopic type (flat elevated, protruded, or elevated with a central depression) and color (milky- or pinkish-white). The gastric adenomas included gastric (11/23, 48%), mixed (4/23, 17%), and intestinal (8/23, 35%) phenotypes. In contrast, no lesions of gastric cancers showed a gastric phenotype (0/9, 0%), while 5 (56%) and 4 (44%) lesions were intestinal and mixed phenotypes, respectively. Gastric cancers were significantly more likely than gastric adenomas to present as reddish depressed lesions with gastric atrophy. All gastric-type adenomas occurred in non-atrophic mucosa, in mucosa with fundic gland polyps in the periphery, in the U or M region, and as flat elevated or protruded lesions with a milky-white color. Half of the lesions increased in size. Meanwhile, the typical endoscopic features of intestinal-type adenomas included occurrence in the L region and elevated pinkish-white lesions with central depression. None of the intestinal-type adenomas increased in size during the observation period. We believe that these endoscopic features will be useful for the prompt diagnosis and appropriate management of gastric neoplasms in patients with FAP

MEDICAL TREATMENT OF UNRUPTURED CEREBRAL ANEURYSMS

Background: Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. Methods: Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. Results: Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. Conclusion: Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed

Arterial spin labeling灌流画像で得られる血管内高信号は内頚動脈の閉塞部位を予測する

Introduction Arterial spin labeling (ASL) involves perfusion imaging using the inverted magnetization of arterial water. If the arterial arrival times are longer than the post-labeling delay, labeled spins are visible on ASL images as bright, high intra-arterial signals (IASs); such signals were found within occluded vessels of patients with acute ischemic stroke. The identification of the occluded segment in the internal carotid artery (ICA) is crucial for endovascular treatment. We tested our hypothesis that high IASs on ASL images can predict the occluded segment. Methods Our study included 13 patients with acute ICA occlusion who had undergone angiographic and ASL studies within 48 h of onset. We retrospectively identified the high IAS on ASL images and angiograms and recorded the occluded segment and the number of high IAS-positive slices on ASL images. The ICA segments were classified as cervical (C1), petrous (C2), cavernous (C3), and supraclinoid (C4). Results Of seven patients with intracranial ICA occlusion, five demonstrated high IASs at C1–C2, suggesting that high IASs could identify stagnant flow proximal to the occluded segment. Among six patients with extracranial ICA occlusion, five presented with high IASs at C3–C4, suggesting that signals could identify the collateral flow via the ophthalmic artery. None had high IASs at C1–C2. The mean number of high IAS-positive slices was significantly higher in patients with intra- than extracranial ICA occlusion. Conclusion High IASs on ASL images can identify slow stagnant and collateral flow through the ophthalmic artery in patients with acute ICA occlusion and help to predict the occlusion site

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

Cシ ノ トクテイ コウレイシャ ニトッテ ケンコウジョウ ノ アンシン トハ

高齢化が進む東北地方のB県C市の特定高齢者にとって"健康上の安心"を構成する要素は何か記述することを目的に、13名の協力者に対し半構成的インタビューを行ない質的に分析した。その結果、安心を構成する要素の中核カテゴリーとして【つながっている】、大カテゴリーとして《人生を認め合える》《今現在のつながりが残っている》《自分の体をやりくりできる》が抽出された。C市の高齢者が健康上安心して生活できるためには、互いに人生を認め合い共に過ごしてきた仲間がいることとそこから生まれた自尊感情が基盤となり、そのつながりに支えられ、更に今現在もそのつながりが残っていることが必要であった。現在のつながりは人や情報、行きたい場所の存在と移動手段などであるが、それらのつながりに支えられて、自分のからだをやりくりできるという自己効力感の存在が認められ、それらが特定高齢者の安心を支えていた。特定高齢者の自己効力感に働きかけ、自尊感情を尊重しながら、活動や参加という場や手段の提供により人や情報とのつながりを維持していくという視点は、ICFの健康の概念である「生活機能-身体状況だけでなく活動・参加-で生きる全体をとらえる」ことに通じていることが明らかになり、これからの高齢者支援の重要な視点として再確認された。The purpose of this study is to identify some factors that make the "tokutei" elderly people living in C city feel secure about their health. Based on interviews with thirteen "tokutei" elders, three major caregories were found as well as a core category that constitutes their secure feeling of "being related to someone or something." Besides these categories, the study also shows that the "tokutei" elderly people have self&#8209;efficacy in their health management. As the notion of ICF suggests, the feeling of "being related" and selfefficacy will bring the elders confidence in their health management. Therefore, these findings should be taken into account when we try to build a support system for the "tokutei" elderly people