Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation

Hyperglycemia is a defining feature of Type 1 and 2 diabetes. Hyperglycemia also causes insulin resistance, and our group (Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB. Am J Physiol Endocrinol Metab Endocrinol Metab 290: E471–E479, 2006) has recently demonstrated that hyperglycemia generated by glucose infusion results in insulin resistance after 5 h but not after 3 h. The aim of this study was to investigate possible mechanism(s) by which glucose infusion causes insulin resistance in skeletal muscle and in particular to examine whether this was associated with changes in insulin signaling. Hyperglycemia (∼10 mM) was produced in cannulated male Wistar rats for up to 5 h. The glucose infusion rate required to maintain this hyperglycemia progressively lessened over 5 h (by 25%, P < 0.0001 at 5 h) without any alteration in plasma insulin levels consistent with the development of insulin resistance. Muscle glucose uptake in vivo (44%; P < 0.05) and glycogen synthesis rate (52%; P < 0.001) were reduced after 5 h compared with after 3 h of infusion. Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3β] over the same time course. In isolated soleus strips taken from control or 1- or 5-h glucose-infused animals, insulin-stimulated 2-deoxyglucose transport was similar, but glycogen synthesis was significantly reduced in the 5-h muscle sample (68% vs. 1-h sample; P < 0.001). These results suggest that the reduced muscle glucose uptake in rats after 5 h of acute hyperglycemia is due more to the metabolic effects of excess glycogen storage than to a defect in insulin signaling or glucose transport.

Population-level perspectives on global change : genetic and demographic analyses indicate various scales, timing, and causes of scyphozoan jellyfish blooms

Whether a perceived increase in the abundance of jellyfishes is related to changing marine environments has been considered primarily using large-scale analyses of multi-species assemblages. Yet jellyfish blooms-rapid increases in the biomass of pelagic coelenterate species-are single-species demographic events. Using published and new genetic analyses and population surveys, we investigate whether there may be a critical knowledge gap between the scales of recent analyses and the scales of natural phenomena. We find that scyphomedusae may show population genetic structure over scales of tens to hundreds of kilometers, that environments vary regionally and locally, and that populations of medusae can display uncorrelated dynamics on these scales. These findings suggest genetic differences between populations and/or environmental differences between sites are important determinants of population dynamics in these jellyfishes. Moreover, the local abundance of medusae may be most strongly correlated with preceding rather than current local environmental conditions, indicating there is a cumulative time-course to the formation of 'blooms'. Broad-scale macro-ecological analyses will need to build from coordinated, long-term, fine-grained studies to synthesize, rather than mask, population-level phenomena in larger-scale analyses. © 2014 Springer International Publishing Switzerland.

PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle

Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)-/- mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5-/- mice developed skeletal muscle insulin resistance, which was associated with ceramide accumulation. Liver insulin sensitivity was improved in Plin5-/- mice, indicating tissue-specific effects of PLIN5 on insulin action. We conclude that PLIN5 plays a critical role in coordinating skeletal muscle triacylglycerol metabolism, which impacts sphingolipid metabolism, and is requisite for the maintenance of skeletal muscle insulin action. © 2014 The Authors.

Laboratory features of common causes of fever in returned travelers

There can be considerable overlap in the clinical presentation and laboratory features of dengue, malaria, and enteric fever, three important causes of fever in returned travelers. Routine laboratory tests including full blood examination (FBE), liver function tests (LFTs), and C-reactive protein (CRP) are frequently ordered on febrile patients, and may help differentiate between these possible diagnoses.

Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. FUNDING: Bill & Melinda Gates Foundation.

A community based systems diagram of obesity causes

INTRODUCTION: Application of system thinking to the development, implementation and evaluation of childhood obesity prevention efforts represents the cutting edge of community-based prevention. We report on an approach to developing a system oriented community perspective on the causes of obesity. METHODS: Group model building sessions were conducted in a rural Australian community to address increasing childhood obesity. Stakeholders (n = 12) built a community model that progressed from connection circles to causal loop diagrams using scripts from the system dynamics literature. Participants began this work in identifying change over time in causes and effects of childhood obesity within their community. The initial causal loop diagram was then reviewed and elaborated by 50 community leaders over a full day session. RESULTS: The process created a causal loop diagram representing community perceptions of determinants and causes of obesity. The causal loop diagram can be broken down into four separate domains; social influences; fast food and junk food; participation in sport; and general physical activity. DISCUSSION: This causal loop diagram can provide the basis for community led planning of a prevention response that engages with multiple levels of existing settings and systems.

Territorial separatism in global politics : causes, outcomes and resolution

This volume examines the various aspects of territorial separatism, focusing on how and why separatist movements arise.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

Don't eat that, you'll get fat! Exploring how parents and children conceptualise and frame messages about the causes and consequences of obesity

Family interactions about weight and health take place against the backdrop of the wider social discourse relating to the obesity epidemic. Parents (and children) negotiate complex and often contradictory messages in constructing a set of beliefs and practices around obesity and weight management. Despite this, very little research attention has been given to the nature of family-unit discourse on the subject of body weight and it's potential influence on the weight-related behaviours of family members. This includes the broad influence that dominant socio-cultural discourses have on family conceptualisations of weight and health. Using in-depth qualitative interviews with 150 family 'groups' comprised of at least one parent and one child in Victoria and South Australia, we explored how parents and children conceptualise and discuss issues of weight- and health-related lifestyle behaviours. Data were analysed using Attride-Stirling's (2001) thematic network approach. Three thematic clusters emerged from the analysis. First, both parents and children perceived that weight was the primary indicator of health. However, parents focused on the negative physical implications of overweight while children focused on the negative social implications. Second, weight and lifestyle choices were highly moralised. Parents saw it as their responsibility to communicate to children the 'dangers' of fatness. Children reported that parents typically used negatively-framed messages and scare tactics rather than positively-framed messages to encourage healthy behaviours. Third was the perception among parents and children that if you were thin, then eating habits and exercise were less important, and that activity could provide an antidote to food choices. Results suggest that both parents and children are internalising messages relating to obesity and weight management that focus on personal responsibility and blame attribution. These views reflect the broader societal discourse, and their consolidation at the family level is likely to increase their potency and make them resistant to change.