Inpatient multidisciplinary care can prevent deterioration of renal function in patients with chronic kidney disease: a nationwide cohort study

BackgroundMultidisciplinary care is necessary to prevent worsening renal function and all-cause mortality in patients with chronic kidney disease (CKD) but has mostly been investigated in the outpatient setting. In this study, we evaluated the outcome of multidisciplinary care for CKD according to whether it was provided in an outpatient or inpatient setting.MethodsThis nationwide, multicenter, retrospective, observational study included 2954 Japanese patients with CKD stage 3–5 who received multidisciplinary care in 2015–2019. Patients were divided into two groups: an inpatient group and an outpatient group, according to the delivery of multidisciplinary care. The primary composite endpoint was the initiation of renal replacement therapy (RRT) and all-cause mortality, and the secondary endpoints were the annual decline in the estimated glomerular filtration rate (ΔeGFR) and the changes in proteinuria between the two groups.ResultsMultidisciplinary care was provided on an inpatient basis in 59.7% and on an outpatient basis in 40.3%. The mean number of health care professionals involved in multidisciplinary care was 4.5 in the inpatient group and 2.6 in the outpatient group (P < 0.0001). After adjustment for confounders, the hazard ratio of the primary composite endpoint was significantly lower in the inpatient group than in the outpatient group (0.71, 95% confidence interval 0.60-0.85, P = 0.0001). In both groups, the mean annual ΔeGFR was significantly improved, and proteinuria significantly decreased 24 months after the initiation of multidisciplinary care.ConclusionMultidisciplinary care may significantly slow deterioration of eGFR and reduce proteinuria in patients with CKD and be more effective in terms of reducing initiation of RRT and all-cause mortality when provided on an inpatient basis

Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells

BACKGROUND: We previously identified a set of genes called ECATs (ES cell-associated transcripts) that are expressed at high levels in mouse ES cells. Here, we examine the expression and DNA methylation of ECATs in somatic cells and germ cells. RESULTS: In all ECATs examined, the promoter region had low methylation levels in ES cells, but higher levels in somatic cells. In contrast, in spite of their lack of pluripotency, male germline stem (GS) cells expressed most ECATs and exhibited hypomethylation of ECAT promoter regions. We observed a similar hypomethylation of ECAT loci in adult testis and isolated sperm. Some ECATs were even less methylated in male germ cells than in ES cells. However, a few ECATs were not expressed in GS cells, and most of them targets of Oct3/4 and Sox2. The Octamer/Sox regulatory elements were hypermethylated in these genes. In addition, we found that GS cells express little Sox2 protein and low Oct3/4 protein despite abundant expression of their transcripts. CONCLUSION: Our results suggest that DNA hypermethylation and transcriptional repression of a small set of ECATs, together with post-transcriptional repression of Oct3/4 and Sox2, contribute to the loss of pluripotency in male germ cells

Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates

内在性レトロウイルス配列によってヒトのエピゲノムが変化してきたことを発見！ --ヒトとチンパンジーのiPS細胞の比較解析から--. 京都大学プレスリリース. 2022-10-12.Changes in the epigenome can affect the phenotype without the presence of changes in the genomic sequence. Given the high identity of the human and chimpanzee genome sequences, a substantial portion of their phenotypic divergence likely arises from epigenomic differences between the two species. In this study, the transcriptome and epigenome were determined for induced pluripotent stem cells (iPSCs) generated from human and chimpanzee individuals. The transcriptome and epigenomes for trimethylated histone H3 at lysine-4 (H3K4me3) and lysine-27 (H3K27me3) showed high levels of similarity between the two species. However, there were some differences in histone modifications. Although such regions, in general, did not show significant enrichment of interspecies nucleotide variations, gains in binding motifs for pluripotency-related transcription factors, especially POU5F1 and SOX2, were frequently found in species-specific H3K4me3 regions. We also revealed that species-specific insertions of retrotransposons, including the LTR5_Hs subfamily in human and a newly identified LTR5_Pt subfamily in chimpanzee, created species-specific H3K4me3 regions associated with increased expression of nearby genes. Human iPSCs have more species-specific H3K27me3 regions, resulting in more abundant bivalent domains. Only a limited number of these species-specific H3K4me3 and H3K27me3 regions overlap with species-biased enhancers in cranial neural crest cells, suggesting that differences in the epigenetic state of developmental enhancers appear late in development. Therefore, iPSCs serve as a suitable starting material for studying evolutionary changes in epigenome dynamics during development

Expression of 20-hydroxyecdysone-induced genes in the silkworm brain and their functional analysis in post-embryonic development

金沢大学理工研究域自然システム学系The insect brain is the center of developmental control, from which ecdysone governs brain morphogenesis and regulates gene expression cascades associated with molting and metamorphosis. In order to identify the 20-hydroxyecdysone (20E)-inducible genes responsible for molting and metamorphosis, we constructed a 20E-induced subtraction complementary DNA library from the fifth instar larval brain of the silkworm Bombyx mori. We isolated 10 genes, designated as bombeil-1 to bombeil-10, three of which did not show any sequence similarity to previously identified Bombyx genes. Whole-mount in situ hybridization revealed that all of these bombeil messenger RNAs were exclusively located in two pairs of lateral neurosecretory cells in the larval brain, known as prothoracicotropic hormone (PTTH)-producing cells. RNA-interference knockdown targeting bombeil-2 resulted in larval-pupal molt defects, and adult wing and leg malformations. These results, together with the cell-specific co-localization of bombeil transcripts with PTTH, suggest that bombeil genes play important roles during larval-pupal-adult development. © 2008 Elsevier Ltd. All rights reserve

Organic electroluminescent diodes as a light source for polymeric integrated devices

Symposium on Integrated Optics, 2001, San Jose, CA, United StatesYutaka Ohmori, Hirotake Kajii, Takahisa Tsukagawa, Katsumi Yoshino, Masanori Ozaki, Akihiko Fujii, Makoto Hikita, Satoru Tomaru, Sabro Imamura, Hisataka Takenaka, Junya Kobayashi, and Fumio Yamamoto "Organic electroluminescent diodes as a light source for polymeric integrated devices", Proc. SPIE 4279, Organic Photonic Materials and Devices III, (15 June 2001). DOI: https://doi.org/10.1117/12.42939

Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells

Deep LearningとALS iPS細胞を用いた疾患予測テクノロジー --人工知能のALS検知・診断への応用--. 京都大学プレスリリース. 2021-02-24.Deep learning amyotrophic lateral sclerosis by taking pictures. 京都大学プレスリリース. 2021-02-24.In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence‐based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research. ANN NEUROL 202

Deep Learning and ALS

In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence-based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research

The bifurcation angle is associated with the progression of saccular aneurysms

The role of the bifurcation angle in progression of saccular intracranial aneurysms (sIAs) has been undetermined. We, therefore, assessed the association of bifurcation angles with aneurysm progression using a bifurcation-type aneurysm model in rats and anterior communicating artery aneurysms in a multicenter case-control study. Aneurysm progression was defined as growth by ≥ 1 mm or rupture during observation, and controls as progression-free for 30 days in rats and ≥ 36 months in humans. In the rat model, baseline bifurcation angles were significantly wider in progressive aneurysms than in stable ones. In the case-control study, 27 and 65 patients were enrolled in the progression and control groups. Inter-observer agreement for the presence or absence of the growth was excellent (κ coefficient, 0.82; 95% CI, 0.61-1.0). Multivariate logistic regression analysis showed that wider baseline bifurcation angles were significantly associated with subsequent progressions. The odds ratio for the progression of the second (145°-179°) or third (180°-274°) tertiles compared to the first tertile (46°-143°) were 5.5 (95% CI, 1.3-35). Besides, the bifurcation angle was positively correlated with the size of aneurysms (Spearman's rho, 0.39; P = 0.00014). The present study suggests the usefulness of the bifurcation angle for predicting the progression of sIAs

Upshaw-Schulman症候群の糸球体障害には補体活性とADAMTS13欠損が関連している可能性がある

Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.博士（医学）・甲第792号・令和3年3月15日Copyright © 2018 Elsevier Ltd. All rights reserved