Mitochondrial dysfunction, inflammation and mutant bone morphogenetic protein receptor (BMPR)2 are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by ...pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC-deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production and glycolysis, induces mitochondrial fission, and a pro-inflammatory state. These features are recapitulated in PAEC from PAH patients with mutant BMPR2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4-12 years old) determined the prevalence ...of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P = 0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's Index--chi 2 linear trend = 59.2, P < 0.0001; body mass index--chi 2 linear trend = 91.6, P < 0.0001; and age-gender-adjusted Japanese standard index of weight for height--chi 2 linear trend = 93.2, P < 0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: chi 2 linear trend = 159, P < 0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.
We report that transgenic mice expressing measles virus nucleocapsid protein (MVNP) in osteoclasts (OCLs) (MVNP mice) are Paget's disease (PD) models and that OCLs from patients with PD and MVNP mice ...express high levels of OCL-derived IGF1 (OCL-IGF1). To determine OCL-IGF1's role in PD and normal bone remodeling, we generated WT and MVNP mice with targeted deletion of Igf1 in OCLs (Igf1-cKO) and MVNP/Igf1-cKO mice, and we assessed OCL-IGF1's effects on bone mass, bone formation rate, EphB2/EphB4 expression on OCLs and osteoblasts (OBs), and pagetic bone lesions (PDLs). A total of 40% of MVNP mice, but no MVNP/Igf1-cKO mice, had PDLs. Bone volume/tissue volume (BV/TV) was decreased by 60% in lumbar vertebrae and femurs of MVNP/Igf1-cKO versus MVNP mice with PDLs and by 45% versus all MVNP mice tested. Bone formation rates were decreased 50% in Igf1-cKO and MVNP/Igf1-cKO mice versus WT and MVNP mice. MVNP mice had increased EphB2 and EphB4 levels in OCLs/OBs versus WT and MVNP/Igf1-cKO, with none detectable in OCLs/OBs of Igf1-cKO mice. Mechanistically, IL-6 induced the increased OCL-IGF1 in MVNP mice. These results suggest that high OCL-IGF1 levels increase bone formation and PDLs in PD by enhancing EphB2/EphB4 expression in vivo and suggest OCL-IGF1 may contribute to normal bone remodeling.
The Standard Specifications for Concrete Structures of the Japan Society of Civil Engineers, which are the main technical standards for the design and construction of concrete structures in the field ...of civil engineering in Japan, have been revised for the first time in five years. This paper gives an outline of the Design and the Materials & Construction editions which were published in March 2018. Besides incorporating technical advances, these revised editions aim to promote deeper coordination among the stages of design, construction and maintenance to promote smoother execution in practice, and more effective handling of issues that involve two or more of these stages. Further, content related to precast concrete, which contributes to higher construction productivity, has been enhanced, and lessons learned from disasters and accidents including the Great East Japan Earthquake are also incorporated.
Objectives Prolonged sitting is a health risk for cardiovascular diseases and all-cause mortality, independent of moderate-to-vigorous physical activity. Epidemiological evaluation of occupational ...sitting has received little attention, even though it may have a potential impact on workers' health. We prospectively examined the association between occupational sitting time and all-cause mortality. Methods Community-dwelling, Japanese workers aged 50-74 years who responded to a questionnaire in 2000-2003 were followed for all-cause mortality through 2011. Cox proportional hazard models were employed to calculate hazard ratios (HR) of all-cause mortality among middle (1-<3 hours/day) or longer (≥3 hours/day) occupationally sedentary subjects by gender or types of engaging industry ("primary industry" and "secondary or tertiary industry"). Results During 368 120 person-years of follow-up (average follow-up period, 10.1 years) for the 36 516 subjects, 2209 deaths were identified. Among workers in primary industry, longer duration of occupational sitting was significantly or marginally associated with higher mortality HR 1.23, 95% confidence interval (95% CI) 1.00-1.51 among men; HR 1.34, 95% CI 0.97-1.84 among women. No associations were found among secondary or tertiary industry workers (men: HR 0.87,95% CI 0.75-1.01 ; women: HR 1.03,95% CI 0.77-1.39). Conclusions Occupational sitting time increased all-cause mortality among primary industry workers, however similar relationships were not observed for secondary-tertiary workers. Future studies are needed to confirm detailed dose-response relationships by using objective measures. In addition, studies using cause-specific mortality data would be important to clarify the physiological underlying mechanism.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, UL, UM, UPUK
A new seawater standard for oceanographic and engineering applications has been developed that consists of three independent thermodynamic potential functions, derived from extensive distinct sets of ...very accurate experimental data. The results have been formulated as Releases of the International Association for the Properties of Water and Steam, IAPWS (1996, 2006, 2008) and are expected to be adopted internationally by other organizations in subsequent years. In order to successfully perform computations such as phase equilibria from combinations of these potential functions, mutual compatibility and consistency of these independent mathematical functions must be ensured. In this article, a brief review of their separate development and ranges of validity is given. We analyse background details on the conditions specified at their reference states, the triple point and the standard ocean state, to ensure the mutual consistency of the different formulations, and the necessity and possibility of numerically evaluating metastable states of liquid water. Computed from this formulation in quadruple precision (128-bit floating point numbers), tables of numerical reference values are provided as anchor points for the consistent incorporation of additional potential functions in the future, and as unambiguous benchmarks to be used in the determination of numerical uncertainty estimates of double-precision implementations on different platforms that may be customized for special purposes.
ABSTRACT
Objectives: To integrate public health nursing (PHN) competencies into a comprehensive performance review instrument for nurses at multiple practice levels in an urban public health ...department.
Design: Based on thorough review of PHN competency literature, the tool evaluates performance for 5 nursing practice classifications (Staff RN, Public Health Nurse, Nurse Practitioner, Clinical Nurse Specialist, Nursing Supervisor) in eight PHN domains (assessment, policy development/program planning, evaluation, communication, cultural competency, partnership/collaboration, disease prevention/health promotion, leadership/systems thinking).
Sample: Tool was piloted with over 50 nurses from PHN workforce (n>400) of Public Health‐Seattle & King County (Washington).
Method: Pilot testing includes all components of the performance appraisal system: Public Health Competency Grid, statement of general workplace expectations, Nursing Performance Appraisal Tool, and supporting documents defining performance elements by job classification.
Results: Supervisors find the tool easy to use and report that it provides opportunity for real communication between employee and supervisor. Nurses at all practice levels report that it effectively describes/evaluates their practice.
Conclusions: This tool is an efficient performance appraisal instrument providing meaningful feedback to nursing employees within a framework of PHN competencies. Adopting such tools in PHN practice can help nurses to better understand their role in population‐based public health efforts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Background: Staged hepatectomy after emergency transcatheter arterial embolization (TAE) has been advocated in ruptured hepatocellular carcinoma (HCC). However, there have been no reports of clinical ...series of this strategy. The purpose of this study was to evaluate the protocol of this therapeutic strategy.
Methods: Sixteen patients with suspected rupture of HCC were included in the study. After emergency TAE, tumor resectability was assessed, followed by staged hepatectomy or repeated TAE. The patients were reevaluated with regard to rupture of HCCs.
Results: Primary hemostasis was achieved successfully in all patients. Eleven patients were finally judged to have experienced HCC rupture. Seven of them underwent staged hepatectomy; the other four underwent repeated TAE because their tumors were considered unresectable. Survival time tended to be longer, but not to a significant extent, in patients who underwent hepatectomy (range, 139 to 1527 days; median, 375 days) than in those treated by TAE alone (range, 43 to 1317 days; median, 158 days).
Conclusions: Staged hepatectomy after TAE is a rational treatment for patients with ruptured HCC. Although TAE is highly effective for initial hemostasis, hepatectomy appears to provide better long-term survival. (Surgery 1998;124:526-35.)
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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