Liver Stiffness Measurements in Patients with Non‐cirrhotic Portal Hypertension – The Devil is In the Details

Non‐cirrhotic portal hypertension (NCPH) is often a diagnostic challenge due to signs and symptoms of portal hypertension that overlap with cirrhosis. The etiology of NCPH is broadly classified as prehepatic, hepatic (pre‐sinusoidal and sinusoidal) and post‐hepatic.1 Some common etiologies of NCPH encountered in clinical practice include portal vein thrombosis (prehepatic) and nodular regenerative hyperplasia (NRH) (hepatic)

グリコーゲンシンターゼキナーゼ-3βの阻害によるc-Mycを介したMGMT promoter メチル化促進に起因する膠芽腫細胞のテモゾロミド感受性増強効果

第12回　高安賞最優秀論文賞受

Long-term exposure to transportation noise in relation to metabolic and cardiovascular outcomes

Transportation noise exposure is increasing because of rapid urbanization and transportation growth. Environmental noise exposure affects a large part of the population and gives rise to widespread annoyance and sleep disturbances. However, the evidence on metabolic and cardiovascular effects of long-term exposure to transportation noise from different sources is mostly limited and of low quality, hampering comprehensive risk assessment, although such effects may be of great public health significance. The main aim of this thesis was to study the development of obesity and cardiovascular outcomes in relation to exposure to noise from road traffic, railways and aircraft, and particularly the role of interactions. The four cohorts under study were based in Stockholm County and included a total of more than 22,000 adults followed for up to 20 years. Three of the papers in the thesis used only one of these cohorts, the SDPP cohort, including close to 8,000 subjects at recruitment. Individual assessment of exposure to noise from road traffic, railways or aircraft was based on a detailed residential history for each study participant as well as a newly developed database containing longitudinal information on determinants of noise levels generated by the three transportation noise sources. Data on air pollution exposure was obtained from dispersion models based on a similar methodology. Information on covariates and health outcomes was based on questionnaires and registers, and the health outcome data were further supplemented with information from clinical investigations. For obesity markers, the strongest associations were observed in relation to aircraft noise. A 10 dB higher level in exposure was associated with a waist circumference increase and weight gain of 0.16 cm/year (95% CI 0.14–0.17) and 0.03 kg/year (95% CI 0.01–0.04), respectively. Road traffic noise exposure was related to a waist circumference increase of 0.04 cm/year (95% CI 0.02–0.06) per 10 dB Lden, while no clear association was observed for railway noise. The incidence rate ratio of central obesity in relation to number of sources of transportation noise exposure increased from 1.22 (95% CI 1.08–1.39) among those exposed to only one source to 2.26 (95% CI 1.55–3.29) among those exposed to all three transportation noise sources. Moreover, aircraft noise exposure was related to incidence of hypertension (hazard ratio: 1.16; 95% CI 1.08–1.24 per 10 dB Lden), but no associations appeared for other transportation noise sources. No clear or consistent associations were observed between transportation noise exposure and risk of ischemic heart disease (IHD) or stroke. However, there appeared to be an increased risk of IHD in women related to road traffic noise exposure, while the opposite held true for men. Higher risks appeared of both IHD and stroke incidence in those exposed to all three noise sources, with hazard ratios of 1.57 (95% CI 1.06–2.32) and 1.42 (95% CI 0.87–2.32), respectively. In conclusion, our findings indicate adverse effects of long-term transportation noise exposure on some metabolic and cardiovascular outcomes, and suggest that combined exposure to different transportation noise sources may be particularly harmful

Glycogen synthase kinase 3β inhibition sensitizes human glioblastoma cells to temozolomide by affecting O6-methylguanine DNA methyltransferase promoter methylation via c-Myc signaling

13301甲第3924号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：Carcinogenesis. 34(10) pp.2206-2217 2013. Oxford University Press. 共著者：Ilya V. Pyko, Mitsutoshi Nakada, Hemragul Sabit, Lei Teng, Natsuki Furuyama, Yutaka Hayashi, Kazuyuki Kawakami, Toshinari Minamoto, Аliaksandr S. Fedulau and Jun-ichiro Hamad

Investigation of putative roles for GSK3b in glioblastoma stemness phenotype and the underlying biological mechanisms

Studies in vitro and in animal model were carried out complementary to optimize treatment of glioblastoma (GBM) by enhancing anti-tumor effect by combination of GSK3β inhibition and temozolomide (TMZ). For in vitro study, we examined effect of GSK3β inhibition and TMZ on patient derived GBM stem-like cells (SCs). I found that GSK3β inhibition enhances effect of TMZ against GBM-SCs and participate in regulation of GBM stemness phenotype. For animal model study, I have developed software pharmacokinetics model and determined optimal concentration of GSK3β inhibitor for continuous intra-tumor infusion by subcutaneous pumps for treatment of orthotopic GBM models and examined the effects of continuous intra-tumor infusion of GSK3β inhibitor, against GBM in mice bearing human GBM-SCs. Our experiments showed that GSK3β inhibition is effective for treatment of experimental GBM generated by inoculation of most malignant GBM-SCs characterized by shortest survival in control animals. We investigated biological mechanisms by which GSK3β regulate GBM stemness phenotype and revealed changes in stem cell markers’ expression in GBM-SCs under GSK3β inhibition, which can be associated with regulation of GBM stemness phenotype by GSK3β via multiple signaling pathways.研究課題/領域番号:18K16553, 研究期間(年度):2018-04-01 - 2020-03-31出典：「Investigation of putative roles for GSK3b in glioblastoma stemness phenotype and the underlying biological mechanisms」研究成果報告書　課題番号18K16553（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18K16553/）を加工して作

Depth‐Related Controls on the Quantitative Composition of Rhodolith Matrices in the High Arctic

ABSTRACT The calcareous matrix of rhodoliths can be composed of one or more crustose coralline algae (CCA) taxa as well as a mixed assemblage of various encrusting organisms. Studies on modern and fossil rhodoliths assume such associations to vary with water depth. Our study explores the quantitative biological composition of calcareous rhodolith matrices along a bathymetric gradient at the Arctic Svalbard archipelago. Using a methodological combination of virtual micro‐CT cross‐sections with a modified point counting approach, we found five different taxonomic groups: CCA, bivalves, serpulids, bryozoans and balanids. While water depth does not influence the general taxon richness as well as the abundance of bivalves, it significantly affects the proportional matrix composition of encrusting organisms by a combination of environmental factors and biological interactions. The decrease in CCA skeletal material with increasing water depth is significantly governed by impaired irradiance conditions. Regular rhodolith movement in shallow waters fosters the proportion of CCA, while decreased movement in deeper waters spurs the proportion of other encrusters. This potentially results from post‐mortem fouling of dead rhodolith parts followed by a recolonization with slow‐growing CCA species Boreolithothamnion glaciale . Our results highlight mechanisms controlling the biogenic composition of calcareous rhodolith matrices and underline the potential of matrices compositions for palaeogeography and palaeobathymetry. Our study contributes to an improved understanding of the composition and developmental patterns of rhodoliths. This can add to a better comprehension of the respective ecosystems on a broader scale and be beneficial for conservation purposes.Dr. Hertha und Helmut Schmauser‐StiftungDF

Road traffic noise and incident ischemic heart disease, myocardial infarction, and stroke:A systematic review and meta-analysis

Background: This systematic review aimed to estimate relative risks for incident ischemic heart disease (IHD), myocardial infarction (MI), and stroke in relation to long-term road traffic noise exposure and to evaluate exposure-response functions. Methods:We systematically searched databases for longitudinal studies in humans on incident IHD, MI, and/or stroke, including quantitative estimates on individual exposure to residential road traffic noise based on validated models or measurements. Risk of bias was evaluated in each study based on predefined criteria. Pooled linear exposure-response functions were generated from random-effect models in meta-analyses of study-specific risk estimates. Restricted cubic spline models were used to capture potential nonlinear associations. Results: Twenty eligible studies were identified based on more than 8.4 million individuals, mostly from Europe, including between 160,000 and 240,000 cases for each of the outcomes. Pooled relative risk estimates were 1.017 (95% confidence interval [CI]: 0.990, 1.044) for IHD, 1.029 (95% CI: 1.011, 1.048) for MI, and 1.025 (95% CI: 1.009, 1.041) for stroke per 10 dB Lden in road traffic noise exposure. Risk estimates appeared higher in combined analyses of studies with a low risk of exposure assessment bias. Restricted cubic spline analyses of these studies showed clear risk increases with exposure for all three cardiovascular outcomes. Conclusions: The evidence indicates that long-term exposure to road traffic noise increases the incidence of IHD, including MI, and stroke. Given the abundant exposure, traffic noise is a cardiovascular risk factor of public health importance. High-quality assessment of noise exposure appears essential for the risk estimation

Two-step algorithm for the automated analysis of fluorescent microscopy data in biomedical applications

© 2017 IEEE. Measurement automation is essential in various biomedical and biotechnological applications become increasingly important with their intensification and wide utilization. Estimation of both pro- and eukaryotic cells subpopulations in different cultures, samples and tissues, including differentiation of live and dead bacterial cells, stem cells in eukaryotic cell culture and so on are essential in multiple biomedical and biotechnological applications. Fluorescent microscopy is a widely used methodology to obtain the above estimates. Wide utilization of biotechnologies increases the importance of automatic microscopic image processing tools design aiming at both qualitative and quantitative assessment of cells sub-populations. Existing methods are mostly based either on cell detection and counting or on the statistical analysis of image areas with similar staining. However, these methods exhibit known drawbacks including their inapplicability to the communities of cells adherent to each other and to external surfaces with biofilms being a prominent example. Another limitation of standard image processing tools in their high level of automation limiting the ability of the operator to adjust the algorithm parameters to particular microscopic imaging conditions as well as to specific features of the studied cells subpopulations. Here we present a two-step algorithm including preliminary adjustment of its parameters to the imaging conditions based on several representative images from the studied cohort in the first step and fully automated analysis of a large series of images with fixed algorithm parameters in the second step. Out results indicate that the suggested methodology is barely sensitive to the decision threshold value that allows to reduce the parameterization of the algorithm