Why e-readers succeeded as a disruptive innovation in the US, but not in Japan

Amazon is part of the answer: in Japan no one offered a large selection of e-books to feed the devices, write Mark E. Parry and Tomoko Kawakam

The BRAF–MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells

The mitogen-activated protein kinase (MAPK) pathway is frequently activated in human cancers, leading to malignant phenotypes such as autonomous cellular proliferation. Here, we demonstrate a novel role of the activated MAPK pathway in immune evasion by melanoma cells with the mutation of BRAF, which encodes a MAPKKs, (BRAFV600E). MEK inhibitor U0126 or RNA interference (RNAi) for BRAFV600E decreased production of the immunosuppressive soluble factors interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to those after signal transducer and activator of transcription (STAT)3 inactivation. The suppressive activity of the culture supernatants from the melanoma cells on the production of inflammatory cytokines IL-12 and tumor necrosis factor α by dendritic cells upon lipopolysaccharide stimulation was markedly reduced after transduction with BRAFV600E RNAi, comparable to the effects observed with STAT3 RNAi transduction. No additive or synergistic effects were observed by the simultaneous transduction of RNAi for both BRAFV600E and STAT3. Furthermore, specific DNA binding and transcriptional activity of STAT3 were not affected by down-regulation of the MAPK signaling with the BRAF RNAi. These results indicate that the MAPK signal, along with the STAT3 signal, is essential for immune evasion by human melanomas that have constitutively active MAPK signaling and is a potential molecular target for overcoming melanoma cell evasion of the immune system

Theoretical Significance of Introduction of Toyota Production System into Medical Service Industries

近年，日本およびアメリカの病院においてトヨタ生産方式（Toyota Production System，以下TPS）の導入が進んでいる。本稿では，このようなTPSの導入現象を医療サービス分野におけるイノベーションの事例として注目し，その理論的意義について論じることを目的としている。以下では，まず初めに，日本およびアメリカにおける医療の現状を概観する。次に，病院のマネジメントとりわけTPSの導入に関する日米の先行研究をレビューし，研究展開の流れと発見事項を整理する。そして最後に，医療サービス分野のマネジメントに関する今後の研究課題と理論的貢献の可能性について論じる

Outer Membrane Vesicles of Helicobacter pylori TK1402 are Involved in Biofilm Formation

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>forms biofilms on glass surfaces at the air-liquid interface in <it>in vitro </it>batch cultures; however, biofilms of <it>H. pylori </it>have not been well characterized. In the present study, we analyzed the ability of <it>H. pylori </it>strains to form biofilms and characterized the underlying mechanisms of <it>H. pylori </it>biofilm formation.</p> <p>Results</p> <p>Strain TK1402 showed strong biofilm forming ability relative to the other strains in Brucella broth supplemented with 7% FCS. The strong biofilm forming ability of TK1402 is reflected the relative thickness of the biofilms. In addition, outer membrane vesicles (OMV) were detected within the matrix of only the TK1402 biofilms. Biofilm formation was strongly correlated with the production of OMV in this strain. We further observed that strain TK1402 did not form thick biofilms in Brucella broth supplemented with 0.2% β-cyclodextrin. However, the addition of the OMV-fraction collected from TK1402 could enhance biofilm formation.</p> <p>Conclusion</p> <p>The results suggested that OMV produced from TK1402 play an important role in biofilm formation in strain TK1402.</p

The treatment effect of endovascular therapy for chronic limb‐threatening ischemia with systemic sclerosis

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients

Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P \u3c 0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P \u3c 0.05). CoPP, in EC-SOD(−/−) mice, enhanced HO activity (P \u3c 0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice

Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis

Purpose: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by a variety of extra-pancreatic involvements which are frequently misdiagnosed as lesions of corresponding organs. The purpose of this study was to clarify the diagnostic imaging features of extra-pancreatic lesions associated with autoimmune pancreatitis. Materials and methods: We retrospectively analyzed diagnostic images of 90 patients with autoimmune pancreatitis who underwent computer-assisted tomography, magnetic resonance imaging, and/or gallium-67 scintigraphy before steroid therapy was initiated. Results: AIP was frequently (92.2%) accompanied by a variety of extra-pancreatic lesions, including swelling of lachrymal and salivary gland lesions (47.5%), lung hilar lymphadenopathy (78.3%), a variety of lung lesions (51.2%), wall thickening of bile ducts (77.8%), peri-pancreatic or para-aortic lymphadenopathy (56.0%), retroperitoneal fibrosis (19.8%), a variety of renal lesions (14.4%), and mass lesions of the ligamentum teres (2.2%). Characteristic findings in CT and MRI included lymphadenopathies of the hilar, peri-pancreatic, and para-aortic regions; wall thickening of the bile duct; and soft tissue masses in the kidney, ureters, aorta, paravertebral region, ligamentum teres, and orbit. Conclusions: Recognition of the diagnostic features in the images of various involved organs will assist in the diagnosis of autoimmune pancreatitis and in differential diagnoses between autoimmune pancreatitis-associated extra-pancreatic lesions and lesions due to other pathologies.ArticleEUROPEAN JOURNAL OF RADIOLOGY. 76(2):228-238 (2010)journal articl

PO-158 Association Of Glucose Metabolism and Physical Activity By Chronotype in Elderly Japanese Adults: There is no full text article associated with this abstract

Objective Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. Although evening chronotype has been reported to be associated with bad glucose control and low physical activity in middle-aged adults, it is not known whether it is true in elderly people. Therefore, the aim of this study was to investigate the relationship between glucose metabolism and physical activity by chronotype (circadian rhythm) in elderly Japanese adults. Methods A cross-sectional study was conducted in 178 adults (72 men and 106 women), aged 60-79 years, who were classified into three chronotype groups, ”definitely morning type (DMT)”, “moderately morning type (MMT)” and “neither type (NET)”, based on the Morningness/Eveningness Questionnaire scores (MEQ-Score). All participants were required to report their daily rhythms of behavior, such as meal time and sleep-wake cycle. Additionally, their physical activity were measured by an uniaxial accelerometer (Kenz Lifecorder EX, SUZUKEN, Nagoya, Japan). Energy intake was assessed by a brief self-administered diet-history questionnaire. Blood was drawn for biochemical analysis after an overnight fast. Results BMI and serum insulin in the DMT group was significantly higher than MMT and NET groups in male. The DMT group had a significantly shorter time interval between dinner and sleep than the other two groups, both in male and female. After adjustment for covariates (age, smoking and alcohol status, energy intakes, moderate-vigorous physical activity (MVPA) and sleep duration), the BMI, serum insulin, fasting blood glucose (FBG) and HOMA-IR in the DMT group was significantly higher than other groups. However, after adjustment for the time interval between dinner and sleep, the significant difference had disappeared. There was significant difference in terms of low-intensity physical activity between male and female. And MVPA in the DMT group, the subjects with low MVPA (&lt;23Mets·hour/week) had higher FBG, serum insulin and HOMA-IR than the subjects with high MVPA (&gt;23Mets·hour/week) in men, but not in women. Conclusions This study demonstrated that the DMT group with early sleep-wake lifestyle had higher BMI, &nbsp;FBG, serum insulin and HOMA-IR, specially in elderly Japanese men with low MVPA, but not in women