Induction of Glucose Metabolism in Stimulated T Lymphocytes Is Regulated by Mitogen-Activated Protein Kinase Signaling

T lymphocytes play a critical role in cell-mediated immune responses. During activation, extracellular and intracellular signals alter T cell metabolism in order to meet the energetic and biosynthetic needs of a proliferating, active cell, but control of these phenomena is not well defined. Previous studies have demonstrated that signaling from the costimulatory receptor CD28 enhances glucose utilization via the phosphatidylinositol-3-kinase (PI3K) pathway. However, since CD28 ligation alone does not induce glucose metabolism in resting T cells, contributions from T cell receptor-initiated signaling pathways must also be important. We therefore investigated the role of mitogen-activated protein kinase (MAPK) signaling in the regulation of mouse T cell glucose metabolism. T cell stimulation strongly induces glucose uptake and glycolysis, both of which are severely impaired by inhibition of extracellular signal-regulated kinase (ERK), whereas p38 inhibition had a much smaller effect. Activation also induced hexokinase activity and expression in T cells, and both were similarly dependent on ERK signaling. Thus, the ERK signaling pathway cooperates with PI3K to induce glucose utilization in activated T cells, with hexokinase serving as a potential point for coordinated regulation

Universal health care no guarantee of equity: Comparison of socioeconomic inequalities in the receipt of coronary procedures in patients with acute myocardial infarction and angina

<p>Abstract</p> <p>Background</p> <p>In Australia there is a socioeconomic gradient in morbidity and mortality favouring socioeconomically advantaged people, much of which is accounted for by ischaemic heart disease. This study examines if Australia's universal health care system, with its mixed public/private funding and delivery model, may actually perpetuate this inequity. We do this by quantifying and comparing socioeconomic inequalities in the receipt of coronary procedures in patients with acute myocardial infarction (AMI) and patients with angina.</p> <p>Methods</p> <p>Using linked hospital and mortality data, we followed patients admitted to Western Australian hospitals with a first admission for AMI (n = 5539) or angina (n = 7401) in 2001-2003. An outcome event was the receipt, within a year, of a coronary procedure—angiography, angioplasty and/or coronary artery bypass surgery (CABG). Socioeconomic status was assigned to each individual using an area-based measure, the SEIFA Index of Disadvantage. Multivariable proportional hazards regression was used to model the association between socioeconomic status and procedure rates, allowing for censoring and adjustment of multiple covariates. Mediating models examined the effect of private health insurance.</p> <p>Results</p> <p>In the AMI patient cohort, socioeconomic gradients were not evident except that disadvantaged women were more likely than advantaged women to undergo CABG. In contrast, in the angina patient group there were clear socioeconomic gradients for all procedures, favouring more advantaged patients. Compared with patients in the most disadvantaged quintile of socioeconomic status, patients in the least disadvantaged quintile were 11% (1-21%) more likely to receive angiography, 52% (29-80%) more likely to undergo angioplasty and 30% (3-55%) more likely to undergo CABG. Private health insurance explained some of the socioeconomic variation in rates.</p> <p>Conclusions</p> <p>Australia's universal health care system does not guarantee equity in the receipt of high technology health care for patients with ischaemic heart disease. While such a system might ensure equity for patients with AMI, where guidelines for treatment are relatively well established, this is not the case for angina patients, where health care may be less urgent and more discretionary.</p

Assessing the impact of prescribed medicines on health outcomes

This paper reviews methods that can be used to assess the impact of medicine use on population health outcomes. In the absence of a gold standard, we argue that a convergence of evidence from different types of studies using multiple methods of independent imperfection provides the best bases for attributing improvements in health outcomes to the use of medicines. The major requirements are: good evidence that a safe and effective medicine is being appropriately prescribed; covariation between medicine use and improved health outcomes; and being able to discount alternative explanations of the covariation (via covariate adjustment, propensity analyses and sensitivity analyses), so that medicine use is the most plausible explanation of the improved health outcomes. The strongest possible evidence would be provided by the coherence of the following types of evidence: (1) individual linked data showing that patients are prescribed the medicine, there are reasonable levels of patient compliance, and there is a relationship between medicine use and health improvements that is not explained by other factors; (2) ecological evidence of improvements in these health outcomes in the population in which the medicine is used. Confidence in these inferences would be increased by: the replication of these results in comparable countries and consistent trends in population vital statistics in countries that have introduced the medicine; and epidemiological modelling indicating that changes observed in population health outcomes are plausible given the epidemiology of the condition being treated

Pacific island regional preparedness for El Niño

The El Niño Southern Oscillation (ENSO) cycle is often blamed for disasters in Pacific island communities. From a disaster risk reduction (DRR) perspective, the challenges with the El Niño part of the ENSO cycle, in particular, are more related to inadequate vulnerability reduction within development than to ENSO-induced hazard influences. This paper analyses this situation, filling in a conceptual and geographic gap in El Niño-related research, by reviewing El Niño-related preparedness (the conceptual gap) for Pacific islands (the geographic gap). Through exploring El Niño impacts on Pacific island communities alongside their vulnerabilities, resiliences, and preparedness with respect to El Niño, El Niño is seen as a constructed discourse rather than as a damaging phenomenon, leading to suggestions for El Niño preparedness as DRR as part of development. Yet the attention which El Niño garners might bring resources to the Pacific region and its development needs, albeit in the short term while El Niño lasts. Conversely, the attention given to El Niño could shift blame from underlying causes of vulnerability to a hazard-centric viewpoint. Instead of focusing on one hazard-influencing phenomenon, opportunities should be created for the Pacific region to tackle wider DRR and development concerns