Advanced glycation inhibition and protection against endothelial dysfunction induced by coumarins and procyanidins from Mammea neurophylla.

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified

Stakeholder perspectives on shale gas fracking: A Q-method study of environmental discourses

The rapid expansion of shale gas exploration worldwide is a significant source of environmental controversy. Successful shale gas policymaking is dependent upon a clear understanding of the dynamics of competing stakeholder perspectives on these issues, and so methods are needed to delineate the areas of agreement and conflict that emerge. This empirical study, based in the United Kingdom, examines emergent perspectives on a range of environmental, health and socio-economic impacts associated with shale gas fracking using Q- methodology: a combined qualitative-quantitative approach. The analysis reveals three typologies of perspectives amongst key industry, civil society and non-affiliated citizen stakeholders; subsequently contextualised in relation to Dryzek’s typology of environmental discourses. These are labelled A) “Don’t trust the fossil fuels industry: campaign for renewables” (mediating between sustainable development and democratic pragmatism discourses); B) “Shale gas is a bridge fuel: economic growth and environmental scepticism” (mediating between economic rationalism and ecological modernisation discourses); and C) “Take place protective action and legislate in the public interest” (reflecting a discourse of administrative rationalism). The implications of these competing discourses for nascent shale gas policy in the UK are discussed in light of recent Government public consultation on changes to national planning policy

The Local Economic Impact of Shale Gas Extraction

Advocates of UK shale gas expansion have focused upon predicted national economic benefits, but local and/or regional impact has been largely neglected. This paper seeks to address this deficit by creating a unique dataset, combining industry data with consumer and supply chain surveys, thereby overcoming the current absence of suitable secondary data. Local economic impact in the Bowland field is estimated via a simple Keynesian local income multiplier model. Results emphasize the importance of facilitating local employment opportunities, through skills initiatives, and development of regional supply chain clusters, to anchor economic benefits within the local economy. Policy implications are discussed

Interest of the task of “Stepping in place” in the assessment of freezing in Parkinson's disease patients

International audienc

INTEREST OF CSF ABETA/TAU INDEX IN ALZHEIMER’S POSITIVE DIAGNOSIS.

International audienceBackground : Alzheimer’s disease (AD) is a devastating neurodegenerative affection that is approaching epidemic proportions in the industrialized world due to aging of the populations. Recently, new revisited AD diagnosis criteria point out the major interest of CSF biomarkers. The dosage of tau, its phosphorylated form p-tau181 and amyloïd Aβ42 peptide in CSF have come to the fore. Based on Aβ42 and tau values obtained using Innogenetics ELSIA kits, a index called IATI could be calculated and seemed very interesting to discriminate AD from other dementias. Aim : To investigate the diagnostic value of CSF IATI in AD positive diagnosis. Method : CSF tau, p-tau181 and Aβ42 biomarkers were analysed in a consecutive cohort of 167 patients with neurological disease. Eighteen AD and 46 non Alzheimer’s dementias were identified in this population. The AD diagnosis was based on NINCDS/ADRDA criteria. Lombar punctures were performed after informed consent was obtained from the patient or the legal representative. The IATI was defined as Aβ42(240+1.18 x tau). The sensitivity, sensibility and ROC analysis were computed. Results : The IATI is considered pathologic if inferior to 1. The IATI sensitivity was above 90% in our series while its specificity was lower, around 60%. On the other hand, p-tau had a better specificity (>90%) but a lower sensitivity (close to 80%). Discussion : Depending on the clinical situation, the utilization of IATI, p-tau or both appears to be very interesting. The IATI<1 provides an excellent sensibility to confirm a positive diagnosis of AD in patients with strong clinical diagnostic presumption. Besides, when the diagnosis is doubtful, p-tau is a useful biomarker to identify AD from other dementias

Increased prevalence of neurocognitive impairment in aging people living with human immunodeficiency virus : the anrs ep58 hand 55-70 study

Background.There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. Methods.This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load -200 cells/uL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in >-2 neurocognitive domains were secondary outcomes of NCI. Results.Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/uL, and median nadir T-CD4 lymphocyte level was 176 cells/uL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). Conclusions.In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications