Robust prognostic prediction model developed with integrated biological markers for acute myocardial infarction

Commonly used prediction methods for acute myocardial infarction (AMI) were created before contemporary percutaneous coronary intervention was recognized as the primary therapy. Although several studies have used machine learning techniques for prognostic prediction of patients with AMI, its clinical application has not been achieved. Here, we developed an online application tool using a machine learning model to predict in-hospital mortality in patients with AMI. A total of 2, 553 cases of ST-elevation AMI were assigned to 80% training subset for cross validation and 20% test subset for model performance evaluation. We implemented random forest classifier for the binary classification of in-hospital mortality. The selected best feature set consisted of ten clinical and biological markers including max creatine phosphokinase, hemoglobin, heart rate, creatinine, systolic blood pressure, blood sugar, age, Killip class, white blood cells, and c-reactive protein. Our model achieved high performance: the area under the curve of the receiver operating characteristic curve for the test subset, 0.95: sensitivity, 0.89: specificity, 0.91: precision, 0.43: accuracy, 0.91 respectively, which outperformed common scoring methods. The freely available application tool for prognostic prediction can contribute to risk triage and decision-making in patient-centered modern clinical practice for AMI

OCT with a Visible Broadband Light Source Applied to High-Resolution Nondestructive Inspection for Semiconductor Optical Devices

Optical coherence tomography with a visible broadband light source (vis-OCT) was developed for high-resolution and nondestructive measurements of semiconductor optical devices. Although a near-infrared (NIR) light source should be used for medical OCT to obtain deep penetration of biological samples, a visible broadband light source is available as a low-coherence light source for industrial products. Vis-OCT provides higher axial resolution than NIR-OCT, because the axial resolution of an OCT image is proportional to the square of the center wavelength of the light source. We developed vis-OCT with an axial resolution of less than 1 μm in air and obtained cross-sectional profiles and images of ridge-type waveguides having heights and widths of several μm. Additionally, we performed cross-sectional measurements and imaging of a stacked semiconductor thin layer. The measured values were similar to those measured by scanning electron microscopy, and the effectiveness of vis-OCT for nondestructive inspection of semiconductor optical devices was demonstrated

骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.博士（医学）・甲第656号・平成28年11月24日© Copyright 2016 American Association of Neurological SurgeonsThe definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250

MicroRNA-494-3p inhibits formation of fast oxidative muscle fibres by targeting E1A-binding protein p300 in human-induced pluripotent stem cells.

MYOD-induced microRNA-494-3p expression inhibits fast oxidative myotube formation by downregulating myosin heavy chain 2 (MYH2) in human induced pluripotent stem cells (hiPSCs) during skeletal myogenesis. However, the molecular mechanisms regulating MYH2 expression via miR-494-3p remain unknown. Here, using bioinformatic analyses, we show that miR-494-3p potentially targets the transcript of the E1A-binding protein p300 at its 3\u27-untranslated region (UTR). Myogenesis in hiPSCs with the Tet/ON-myogenic differentiation 1 (MYOD1) gene (MyoD-hiPSCs) was induced by culturing them in doxycycline-supplemented differentiation medium for 7 days. p300 protein expression decreased after transient induction of miR-494-3p during myogenesis. miR-494-3p mimics decreased the levels of p300 and its downstream targets MYOD and MYH2 and myotube formation efficiency. p300 knockdown decreased myotube formation efficiency, MYH2 expression, and basal oxygen consumption rate. The binding of miR-494-3p to the wild type p300 3\u27-UTR, but not the mutated site, was confirmed using luciferase assay. Overexpression of p300 rescued the miR-494-3p mimic-induced phenotype in MyoD-hiPSCs. Moreover, miR-494-3p mimic reduced the levels of p300, MYOD, and MYH2 in skeletal muscles in mice. Thus, miR-494-3p might modulate MYH2 expression and fast oxidative myotube formation by directly regulating p300 levels during skeletal myogenesis in MyoD-hiPSCs and murine skeletal muscle tissues

Ketone bodies : A double-edged sword for mammalian life span.

Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role of endogenous ketogenesis in mammalian life span, and the safety and efficacy of the long-term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole-body Hmgcs2 deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3-butanediol, a precursor of β-hydroxybutyrate. Furthermore, feeding the 1,3-butanediol-containing diet from early in life increases midlife mortality in normal mice, but in aged mice it extends life span and prevents the high mortality associated with atherosclerosis in ApoE-deficient mice. By contrast, an ad libitum low-carbohydrate ketogenic diet markedly increases mortality. In conclusion, endogenous ketogenesis affects mammalian survival, and ketone body supplementation may represent a double-edged sword with respect to survival, depending on the method of administration and health status

地震発生帯における深部掘削孔を用いた長期計測

Large earthquakes occur frequently in subduction zones. Most earthquakes are generated in the seismogenic zone, a fairly limited area confined to the shallower regions of the subduction plate boundary. To understand the processes of earthquake generation, it is essential to monitor the physical and mechanical properties of the seismogenic zone over long periods. At present, there are no deep borehole observations of the seismogenic zone more than 3km below seafloor, because it has, until now, been impossible to penetrate to such depths below the sea floor. The Integrated Ocean Drilling Program (IODP), scheduled to begin in 2003, plans to drill boreholes beneath the ocean floor using a multiple-drilling platform operation. The IODP riser-quipped drilling ship (Chikyu) enables the emplacement of boreholes up to 0km beneath the ocean floor, and will provide opportunities to conduct long-term deep borehole observations in the seismogenic zone. Long-term borehole observations in the seismogenic zone are expected to require the development of advanced sampling, monitoring, and recording technology. Here, we discuss the scientific objectives, engineering and technical challenges, and experimental design for a deep borehole, long-term deepborehole monitoring system aimed at understanding the processes of earthquake generation in the seismogenic zone of subduction plate boundaries. We focus specifically on the relationships between environmental conditions in the deep subsurface, details of monitoring and recording, and design and implementation of scientific tools and programs

リゾフォスファチジルコリンはヒトTリンパ球におけるヘパリン結合性表皮増殖因子様増殖因子の発現を増加する

京都大学0048新制・課程博士博士(医学)甲第6805号医博第1905号新制||医||666(附属図書館)15877UT51-97-H189京都大学大学院医学研究科内科系専攻(主査)教授 淀井 淳司, 教授 篠山 重威, 教授 北 徹学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Nardilysin prevents amyloid plaque formation by enhancing α-secretase activity in an Alzheimer's disease mouse model.

Amyloid beta (Aβ) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Alpha-cleavage of APP by α-secretase has a potential to preclude the generation of Aβ because it occurs within the Aβ domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances α-cleavage of APP, which results in the decreased generation of Aβ in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents Aβ deposition in the AD mouse model. The activity of α-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the Aβ plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls Aβ formation through the regulation of α-secretase