The short-chain fatty acid uptake fluxes by mice on a guar gum supplemented diet associate with amelioration of major biomarkers of the metabolic syndrome

Studies with dietary supplementation of various types of fibers have shown beneficial effects on symptoms of the metabolic syndrome. Short-chain fatty acids (SCFAs), the main products of intestinal bacterial fermentation of dietary fiber, have been suggested to play a key role. Whether the concentration of SCFAs or their metabolism drives these beneficial effects is not yet clear. In this study we investigated the SCFA concentrations and in vivo host uptake fluxes in the absence or presence of the dietary fiber guar gum. C57Bl/6J mice were fed a high-fat diet supplemented with 0%, 5%, 7.5% or 10% of the fiber guar gum. To determine the effect on SCFA metabolism, C-13-labeled acetate, propionate or butyrate were infused into the cecum of mice for 6 h and the isotopic enrichment of cecal SCFAs was measured. The in vivo production, uptake and bacterial interconversion of acetate, propionate and butyrate were calculated by combining the data from the three infusion experiments in a single steady-state isotope model. Guar gum treatment decreased markers of the metabolic syndrome (body weight, adipose weight, triglycerides, glucose and insulin levels and HOMA-IR) in a dose-dependent manner. In addition, hepatic mRNA expression of genes involved in gluconeogenesis and fatty acid synthesis decreased dose-dependently by guar gum treatment. Cecal SCFA concentrations were increased compared to the control group, but no differences were observed between the different guar gum doses. Thus, no significant correlation was found between cecal SCFA concentrations and metabolic markers. In contrast, in vivo SCFA uptake fluxes by the host correlated linearly with metabolic markers. We argue that in vivo SCFA fluxes, and not concentrations, govern the protection from the metabolic syndrome by dietary fibers

Synthesis and review: tackling the nitrogen management challenge: from global to local scales

One of the 'grand challenges' of this age is the anthropogenic impact exerted on the nitrogen cycle. Issues of concern range from an excess of fixed nitrogen resulting in environmental pressures for some regions, while for other regions insufficient fixed nitrogen affects food security and may lead to health risks. To address these issues, nitrogen needs to be managed in an integrated fashion, at a variety of scales (from global to local). Such management has to be based on a thorough understanding of the sources of reactive nitrogen released into the environment, its deposition and effects. This requires a comprehensive assessment of the key drivers of changes in the nitrogen cycle both spatially, at the field, regional and global scale and over time. In this focus issue, we address the challenges of managing reactive nitrogen in the context of food production and its impacts on human and ecosystem health. In addition, we discuss the scope for and design of management approaches in regions with too much and too little nitrogen. This focus issue includes several contributions from authors who participated at the N2013 conference in Kampala in November 2013, where delegates compiled and agreed upon the 'Kampala Statement-for-Action on Reactive Nitrogen in Africa and Globally'. These contributions further underline scientifically the claims of the 'Kampala Statement', that simultaneously reducing pollution and increasing nitrogen available in the food system, by improved nitrogen management offers win-wins for environment, health and food security in both developing and developed economies. The specific messages conveyed in the Kampala Statement focus on improving nitrogen management (I), including the reduction of nitrogen losses from agriculture, industry, transport and energy sectors, as well as improving waste treatment and informing individuals and institutions (II). Highlighting the need for innovation and increased awareness among stakeholders (III) and the identification of policy and technology solutions to tackle global nitrogen management issues (IV), this will enable countries to fulfil their regional and global commitments

The European Nitrogen Problem in a Global Perspective

Nature of the problem (science/management/policy): Reactive nitrogen has both positive and negative effects on ecosystem and human health. Reactive nitrogen is formed through the use of fossil fuels releasing large amounts of nitrogen oxides into the atmosphere and through the production of ammonia by the Haber-Bosch process and using it in agriculture to increase our food, feed and fuel production. While the use of nitrogen as a fertilizer has brought enormous benefits, losses of fertilizer nitrogen and combustion nitrogen to the environment lead to many side effects on human health, ecosystem health, biodiversity and climate. Approaches: The European nitrogen problem is placed in a global perspective, showing the European nitrogen fixation, transport and environmental impacts compared to different regions of the globe. Key findings/state of knowledge: An overview is provided of the nitrogen issues and challenges in Europe and places them in a broader global context. Europe is one of the leading producers of reactive nitrogen, but it is also the first region in the world where the issue was recognized and in some parts of Europe the reactive nitrogen losses to the environment started to decrease. There is a clear policy on reducing nitrogen oxide emissions that led to reductions by implementation of end of pipe technology. Fertilizer production and use decreased in Europe in the early 1990s, in particular, due to the economic recession in the Eastern part of Europe. Currently, the fertilizer use in EU25 is about 12 Mton, which is 4 Mton lower than in the 1980s and gradually increasing. The nitrogen use efficiency of nitrogen in the EU, defined as the net output of N in products divided by the net input is about 36%. This is lower than the world average (50%) as fertilization rates are much higher. Major uncertainties/challenges: The effects related to losses of nitrogen in Europe include the exceedance of critical loads and the resulting biodiversity loss, ground water pollution and eutrophication of ecosystems; eutrophication of open waters and coastal areas resulting in algae blooms and fish kills; increased levels of NOx and aerosols in the atmosphere resulting in human health impacts and climate change; and the increased emissions of the greenhouse gas nitrous oxide resulting in climate change. Nitrogen also affects the biogeochemical cycles of other components such as carbon. Recommendations (research/policy): The complexity of multi-pollutant ¿ multiple-effect interactions is a major hurdle to improving public awareness.JRC.H.1-Water Resource

European Nitrogen Assessment - Technical Summary

A century ago, when the world depended on fossil nitrogen and manure recycling, there wasinsuffi cient reactive nitrogen to feed the growing human population. With the invention of theHaber–Bosch process, humans found a way to make cheap reactive nitrogen from the almostinexhaustable supply of atmospheric di-nitrogen. What humans did not anticipate was that themassive increase in reactive nitrogen supply, exacerbated by fossil fuel burning, would lead toa web of new environmental problems cutting across all global-change challenges.Th e European Nitrogen Assessment presents the fi rst full, continental-scale assessmentof reactive nitrogen in the environment and sets the problem in context by providing amultidisciplinary introduction to the key processes in the nitrogen cycle. Issues of up-scalingfrom fi eld, farm and city to national and continental scales are addressed in detail withemphasis on opportunities for better management at local to global levels. A comprehensiveseries of maps showing nitrogen pools and fl uxes across Europe also highlight the locationof the major threats and allow a comparison of national budgets for the fi rst time. Five keysocietal threats posed by reactive nitrogen are assessed, providing a framework for a set ofpolicies that can be used for joined-up management of the nitrogen cycle in Europe. Th isincludes the fi rst cost–benefi t analysis for diff erent reactive nitrogen forms and considerationof future scenarios.JRC.DDG.H.2-Climate change and air qualit

Western-style diet does not negatively affect the healthy aging benefits of lifelong restrictive feeding

BACKGROUND: Lifelong consumption of a Western-style diet is a risk factor for developing metabolic disorders and therefore impairs healthy aging. Dietary restriction (DR) could delay the onset of age-related diseases and prolong life span, however, the extent to which this depends on diet type is poorly understood. OBJECTIVE: To study whether feeding a Western-style diet affects the healthy aging benefits of DR. METHODS: Mice fed a Western-style diet (ad libitum and DR) were compared to those fed a standard healthy diet (ad libitum and DR). Survival and several metabolic and endocrine parameters were analyzed. RESULTS: Lifelong consumption of a Western-style diet resulted in increased adiposity, elevated triglyceride levels in plasma, higher homeostatic model assessment-insulin resistance and higher resting metabolic rate in mice compared to the standard diet group. This was accompanied by reduced survival in the Western-style diet group. DR irrespective of diet type improved abovementioned parameters. CONCLUSIONS: Lifelong restricted consumption of Western-style diet led to improved metabolic and endocrine parameters, and increased survival compared to the ad libitum Western-style diet group. Interestingly, the survival was comparable in restricted Western-style and standard diet groups, suggesting that reduced food intake rather than diet composition play more important role in promoting longevity/survival

Nitrogen in Current European Policies

Europe, and especially the European Union (EU), has many governmental policy ¿ measures aimed at decreasing unwanted reactivenitrogen (N r ) emissions from combustion, agriculture and urban wastes. Many of these policy measures have an ¿eff ects-basedapproach¿, and focus on single N r compounds, single sectors and either on air or waters.¿ Th is chapter addresses the origin, objectives and targets of EU policy measures related to Nr emissions, considers which instrumentsare being used to implement the policies and briefl y discusses the eff ects of the policy measures.Approaches¿ Th e chapter starts with a brief description of the basic elements of governmental policy measures.¿ A review of the main international conventions and EU policies related to emissions of Nr to air and water is then provided.¿ Finally the chapter provides a semi-quantitative assessment of the eff ectiveness and effi ciency of European policy measures.Key fi ndings/state of knowledge¿ International conventions and other treaties have played a key role in raising awareness and establishing policy measures for Nr emissionsabatement in EU through so-called Directives and Regulations.¿ Th ere are many diff erent EU Directives, oft en addressing individual Nr compounds from individual sectors (e.g. NOx emissions fromcombustion; NH 3 emissions from agriculture, pollution of groundwater and surface water by nitrates from agriculture, discharge oftotal nitrogen from urban sewage to surface waters).¿ Many EU Directives have been revised following review and evaluation. Th ere are increasing eff orts to cluster single EU Directives intolarger Framework Directives.¿ Compliance with, and eff ectiveness of, the Directives diff ers between sectors; it decreases in the order (i) reducing NO x emissions fromcombustion sources, (ii) reducing nitrogen (and especially Phosphorus) discharges to waters from industries and households, and (iii)reducing NH 3 emissions and NO 3 leaching from agriculture.¿ Th ere is not much literature on the diff erences in the eff ectiveness and effi ciencies of Directives; a number of factors seem to be involvedin eff ectiveness and effi ciency, but these have not yet been analysed in a coherent manner.Major uncertainties/challenges¿ Th ere is a huge diversity in N r emission sources and pathways, while the number of policy instruments is limited. Th ere is need to fi ndthe optimal mix of policy instruments targeted to the emission sources as well as the stakeholders involved.¿ It has been indicated that some EU Directives addressing emissions of nitrogen compounds from specifi c sources have antagonisticeff ects. Th e magnitude of these eff ects is not yet well known.¿ Th ere is a delay in the environmental and ecological responses following the introduction of Directives; these are due to legislativedelays, lack of enforcement and control, constraints in practice and because of biogeochemical hysteresis eff ects; these eff ects are notyet well understood quantitatively.¿ In general, only modest reductions in Nr emissions from agriculture have been achieved to date; this refl ects the need for more eff ectiveand effi cient policy measures and/or greater enforcement of current policies.Recommendations¿ To examine further the diff erences between sectors of the factors that contribute to the eff ectiveness and effi ciency of policy measuresfor the abatement of N r emissions.¿ T o explore further the eff ectiveness and effi ciency of more integrated N management and integrated policy measures for the abatementof adverse impacts of N r emissions.JRC.DDG.H.2-Climate change and air qualit

Non-Invasive Visualization of the Cardiac Venous System in Coronary Artery Disease Patients Using 64-Slice Computed Tomography

ObjectivesThis study was designed to evaluate the value of 64-slice computed tomography (CT) to visualize the cardiac veins and evaluate the relation between variations in venous anatomy and history of infarction.BackgroundCardiac resynchronization therapy (CRT) is an attractive treatment for selected heart failure patients. Knowledge of venous anatomy may help in identifying candidates for successful left ventricular lead implantation.MethodsThe 64-slice CT of 100 individuals (age 61 ± 11 years, 68% men) was studied. Subjects were divided into 3 groups: 28 control patients, 38 patients with significant coronary artery disease (CAD), and 34 patients with a history of infarction. Presence of the following coronary sinus (CS) tributaries was evaluated: posterior interventricular vein (PIV), posterior vein of the left ventricle, and left marginal vein (LMV). Vessel diameters were also measured.ResultsCoronary sinus and PIV were identified in all individuals. Posterior vein of the left ventricle was observed in 96% of control patients, 84% of CAD patients, and 82% of infarction patients. In patients with a history of infarction, a LMV was significantly less observed as compared with control patients and CAD patients (27% vs. 71% and 61%, respectively, p < 0.001). None of the patients with lateral infarction and only 22% of patients with anterior infarction had a LMV. Regarding quantitative data, no significant differences were observed between the groups.ConclusionsNon-invasive evaluation of cardiac veins with 64-slice CT is feasible. There is considerable variation in venous anatomy. Patients with a history of infarction were less likely to have a LMV, which may hamper optimal left ventricular lead positioning in CRT implantation

Connected Growth: developing a framework to drive inclusive growth across a city-region

This ‘in perspective’ piece addresses the (re-)positioning of civil society within new structures of city-region governance within Greater Manchester (GM). This follows on from the processes of devolution, which have given the Greater Manchester City-Region (GMCR) a number of new powers. UK devolution, to date, has been largely focused upon engendering agglomerated economic growth at the city-region scale. Within GMCR, devolution for economic development has sat alongside the devolution of health and social care (unlike any other city-region in the UK) as well. Based on stakeholder mapping and semi-structured interviews with key actors operating across the GMCR, the paper illustrates how this has created a number of significant tensions and opportunities for civil society actors, as they have sought to contest a shifting governance framework. The paper, therefore, calls for future research to carefully consider how civil society groups are grappling with devolution; both contesting and responding to devolution. This is timely given the shifting policy and political discourse towards the need to deliver more socially-inclusive city-regions

Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor. and Glucagon-Like Peptide-1

The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention

Acute Beneficial Hemodynamic Effects of a Novel 3D-Echocardiographic Optimization Protocol in Cardiac Resynchronization Therapy

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT