G-Protein coupled receptor signalling in pluripotent stem cell-derived cardiovascular cells: Implications for disease modelling

Human pluripotent stem cell derivatives show promise as an in vitro platform to study a range of human cardiovascular diseases. A better understanding of the biology of stem cells and their cardiovascular derivatives will help to understand the strengths and limitations of this new model system. G-protein coupled receptors (GPCRs) are key regulators of stem cell maintenance and differentiation and have an important role in cardiovascular cell signaling. In this review, we will therefore describe the state of knowledge concerning the regulatory role of GPCRs in both the generation and function of pluripotent stem cell derived-cardiomyocytes, -endothelial, and -vascular smooth muscle cells. We will consider how far the in vitro disease models recapitulate authentic GPCR signaling and provide a useful basis for discovery of disease mechanisms or design of therapeutic strategies

Indocyanine green elimination test in orthotopic liver recipients.

OBJECTIVE: To determine its predictive capability on graft quality and resultant clinical outcome, the indocyanine green (ICG) elimination test was performed by a spectrophotometric method and a noninvasive finger-piece method with 50 orthotopic liver transplantations. BACKGROUND: Early detection of poor-functioning hepatic grafts is one of the most important issues in liver transplantation, but no reliable methods exist. METHODS: The ICG test was performed after 50 orthotopic liver transplantations on postoperative days 1, 3, and 7. Indocyanine green elimination constants (K(ICG)) were measured by both a standard spectrophotometric analysis (K(ICG)-B) and by a finger-piece method (K(ICG)-F). The patients were followed for a minimum of 3 months after transplantation. Results of ICG tests were correlated with various clinical determinations. RESULTS: Twelve of the 50 grafts were lost within three months, of which 7 were related to graft failure. Multivariate analysis using the Cox proportional hazard model revealed that K(ICG) on postoperative day 1 was a better predictor of liver-related graft outcome than any of the conventional liver function tests. Furthermore, K(ICG) values showed significant correlation with the severity of preservation injury, longer intensive care unit (ICU) and hospital stay, prolonged liver dysfunction, and septic complications. Correlation of K(ICG) values by the spectrophotometric method with those by the finger-piece method was highly satisfactory in the grafts that had K(ICG)-B <0.15 min-1 (y = 0.868x -0.011, r = .955). CONCLUSION: The ICG elimination test, conducted spectrophotometrically or optically on the day after liver transplantation, is a reliable indicator of graft quality and subsequent graft outcome early after liver transplantation

Early death or retransplantation in adults after orthotopic liver transplantation: Can outcome be predicted?

Early, reliable outcome prediction after a liver transplant would help improve organ use by minimizing unnecessary retransplantations. At the same time, early intervention in those cases destined to fail may ameliorate the high morbidity and mortality associated with retransplantation. The purpose of this study was to analyze several parameters that have been identified in the past as being associated with patient and graft outcome, and to try to develop a model that would allow us to make predictions based on data available in the early postoperative period. A total of 148 patients were followed in a prospective, observational study. Graft failure was defined as patient death or retransplantation within 3 months of surgery. Preoperative variables studied included patient demographics, need for life support, presence of ascites, serum bilirubin, serum albumin, prothrombin time, serum creatinine, and the results of the cytotoxic crossmatch. During the first 5 postoperative days, standard measurements included serum transaminases, serum bilirubin, ketone body ratio, prothrombin time, factor V, and serum lactate. Oxygen consumption was measured shortly after surgery, once the patients had rewarmed to 36°C. There were 131 successful transplants (88.5%) and 17 failures (11.5%). Most of the variables studied were found to be associated with outcome (by univariate analysis) at different points in the early postoperative period. However, receiver operating characteristic curve analysis showed that the predictive ability of even the best parameter was not adequate to make decisions on individual patients. Multivariate analysis, using stepwise logistic regression, yielded a model with an overall accuracy of 92.7%. Again, receiver operating characteristic curve analysis suggested that this model did not achieve the discriminating power needed for routine clinical use. We are still not able to accurately predict outcome in the early posttransplant period. We must be very careful when evaluating parameters, or scoring systems, that are said to accomplish this. It is especially important in this era of cost containment, with its renewed pressures to guide therapy based on our perceived understanding of a patient’s future clinical course. © 1994 by Williams & Wilkins

Do Multinational enterprises push up wages of domestic firms in the Italian Manufacturing sector?

This paper analyzes the effects of foreign direct investment on wages paid by domestic firms in the Italian manufacturing sector over the period 2002–2007. In particular, the authors investigate the im-pact of multinational enterprises on wages paid by local firms which operate in the same industry, known and horizontal wage spillovers, or have linkages with multinational enterprises in both downstream and upstream industries, known as vertical wage spillovers. By using a large panel dataset, consisting of 551,000 observations, the authors find evidence of wage spillovers only at inter-industry level and, more specifically, for those firms who supply their goods to multinational enterprises, described as backward wage spillovers. Moreover, findings suggest that the wage spillover effect is strongly affected by the technological gap between local and foreign firms: only workers employed in domestic firms with a low-medium technological absorptive capacity seem to benefit from the presence of multinational enterprises in terms of higher wages

Responding to Climate Change: The Economy and Economics - Part of the Problem and Solution

The Climate Change Starter’s Guide provides an introduction and overview for education planners and practitioners on the wide range of issues relating to climate change and climate change education, including causes, impacts, mitigation and adaptation strategies, as well as some broad political and economic principles. The aim of this guide is to serve as a starting point for mainstreaming climate change education into school curricula. It has been created to enable education planners and practitioners to understand the issues at hand, to review and analyse their relevance to particular national and local contexts, and to facilitate the development of education policies, curricula, programmes and lesson plans. The guide covers four major thematic areas: 1. the science of climate change, which explains the causes and observed changes; 2. the social and human aspects of climate change including gender, health, migration, poverty and ethics; 3. policy responses to climate change including measures for mitigation and adaptation; and 4. education approaches including education for sustainable development, disaster reduction and sustainable lifestyles. A selection of key resources in the form of publication titles or websites for further reading is provided after each of the thematic sections

Arterioportal fistula following liver biopsy - Three cases occurring in liver transplant recipients

Although liver biopsy is a very useful procedure used frequently in the diagnosis and management of liver dysfunction occurring after orthotopic liver transplantation, complications can occur with its use. An unusual complication of arterioportal fistula is reported here. Based upon this small series of an unusual event and the knowledge that the posttransplant liver may be more hypervascular than prior to OLTx and that it is uniquely susceptible to hepatic infarction and abscess formation, any attempt at fistula closure should be considered carefully prior to initiating the therapy (15). Unless a serious complication occurs [such as a transient biliary obstruction due to hemobilia as occurred in case 2, portal hypertension as also occurred in case 2, or systemic sepsis or other symptoms develop related directly to the fistula], simple observation may be the best choice of action. Should therapy be required, hepatic arterial embolization should be reserved for adults with intrahepatic fistulas. Primary surgical closure of intrahepatic fistula should be reserved for cases of extrahepatic fistula. © 1995 Plenum Publishing Corporation