Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents

Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and D-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.

Direct and indirect effects of pathological gambling on risk attitudes

We study individual decision making in a lottery-choice task performed by three different populations: gamblers under psychological treatment ("addicts"), gamblers’ spouses ("victims"), and people who are neither gamblers or gamblers’ spouses ("normals"). We find that addicts are willing to take less risk than normals, but the difference is smaller as a gambler’s time under treatment increases. The large majority of victims report themselves unwilling to take any risk at all. However, addicts in the first year of treatment react more than other addicts to the different values of the risk-return parameter.

Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Comparison of child morbidity in two contrasting medieval cemeteries from Denmark

This study compares associations between demographic profiles, long bone lengths, bone mineral content, and frequencies of stress indicators in the preadult populations of two medieval skeletal assemblages from Denmark. One is from a leprosarium, and thus probably represents a disadvantaged group (Naestved). The other comes from a normal, and in comparison rather privileged, medieval community (AEbelholt). Previous studies of the adult population indicated differences between the two skeletal collections with regard to mortality, dental size, and metabolic and specific infectious disease. The two samples were analyzed against the view known as the "osteological paradox" (Wood et al. [1992] Curr. Anthropol. 33:343-370), according to which skeletons displaying pathological modification are likely to represent the healthier individuals of a population, whereas those without lesions would have died without acquiring modifications as a result of a depressed immune response. Results reveal that older age groups among the preadults from Naestved are shorter and have less bone mineral content than their peers from AEbelholt. On average, the Naestved children have a higher prevalence of stress indicators, and in some cases display skeletal signs of leprosy. This is likely a result of the combination of compromised health and social disadvantage, thus supporting a more traditional interpretation. The study provides insights into the health of children from two different biocultural settings of medieval Danish society and illustrates the importance of comparing samples of single age groups.

Issues of water supply and contemporary urban society: the case of Greater Amman, Jordan

Over the last two decades, Jordan has suffered a chronic water crisis, and is the tenth most water-scarce nation on Earth. Such water stress has been well illustrated in the case of Greater Amman, the capital, which has grown dramatically from a population of around 2000 in the 1920s, to 2.17 million today. One of the distinctive characteristics of the water supply regime of Greater Amman is that since 1987 it has been based on a system of rationing, with households receiving water once a week for various durations. Amman is highly polarized socio-economically, and by means of household surveys, both quantitative and qualitative, conducted in high- and low-income divisions of the city, a detailed empirical evaluation of the storage and use of water, the strategies used by households to manage water and overall satisfaction with water supply issues is provided in this paper, looking specifically at issues of social equity. The analysis demonstrates the social and economic costs of water rationing and consequent management to be high, as well as emphasizing that issues of water quality are of central importance to all consumers regardless of their socio-economic status within the city.