Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins

Aims/hypothesis: Previous studies have shown that glycation of LDL by methylglyoxal and glycolaldehyde, in the absence of significant oxidation, results in lipid accumulation in macrophage cells. Such 'foam cells' are a hallmark of atherosclerosis. In this study we examined whether LDL glycation by methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be inhibited by agents that scavenge reactive carbonyls. Such compounds may have therapeutic potential in diabetes-associated atherosclerosis. Materials and methods: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine. LDL modification was characterised by changes in mobility (agarose gel electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages was assessed by HPLC. Results: Inhibition of LDL glycation was detected with equimolar or greater concentrations of the scavengers over the reactive carbonyl. This inhibition was structure-dependent and accompanied by a modulation of cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's reagent P and hydralazine, cellular sterol levels returned to control levels despite incomplete inhibition of LDL modification. Conclusions/ interpretation: Inhibition of LDL glycation by interception of the reactive aldehydes that induce LDL modification prevents lipid loading and model foam cell formation in murine macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis. © Springer-Verlag 2006

Radically Relational: Using Textiles As A Platform To Develop Methods For Embodied Design Processes

This position paper builds on textiles as a metaphor to explore the experiential knowledge observed through embodied design processes. In order to build understanding, we have tailored our tools and methods to support our explorations so far. As literature shows articulating our sensory experiences with materials is a challenging task. In order to support our investigations, in this paper we present a reflection on our diverse approaches to introduce tools that support us in interrogating how designers relate with materials, particularly textiles, and use their sensorial body to experience them during the creative process. We build on our previous research that identified relevant embodied process to textile selection, and reflect on how we have explored how sensing technology can augment and empower each of these phases, to support the design process. We conclude by discussing the learning outcomes from introducing such tools, in order to reflect on the future of our research

Comparing behavior under risk and under ambiguity in a lifecycle experiment

Experiments on intertemporal consumption typically show that people have difficulties in optimally solving such problems. Previous studies have focused on contexts in which agents are faced with risky future incomes and have to plan over long horizons. We present an experiment comparing decision making under certainty, risk, and ambiguity, over a shorter lifecycle. Results show that behavior in the ambiguity treatment is markedly different than in the risk condition and it is characterized by a significant pattern of under-consumption

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Rapidly rotating second-generation progenitors for the blue hook stars of {\omega} Cen

Horizontal Branch stars belong to an advanced stage in the evolution of the oldest stellar galactic population, occurring either as field halo stars or grouped in globular clusters. The discovery of multiple populations in these clusters, that were previously believed to have single populations gave rise to the currently accepted theory that the hottest horizontal branch members (the blue hook stars, which had late helium-core flash ignition, followed by deep mixing) are the progeny of a helium-rich "second generation" of stars. It is not known why such a supposedly rare event (a late flash followed by mixing) is so common that the blue hook of {\omega} Cen contains \sim 30% of horizontal branch stars 10 , or why the blue hook luminosity range in this massive cluster cannot be reproduced by models. Here we report that the presence of helium core masses up to \sim 0.04 solar masses larger than the core mass resulting from evolution is required to solve the luminosity range problem. We model this by taking into account the dispersion in rotation rates achieved by the progenitors, whose premain sequence accretion disc suffered an early disruption in the dense environment of the cluster's central regions where second-generation stars form. Rotation may also account for frequent late-flash-mixing events in massive globular clusters.Comment: 44 pages, 8 figures, 2 tables in Nature, online june 22, 201

Parenthood and factors that influence outdoor recreational physical activity from a gender perspective

Background: A physically active life promotes both physical and mental health, increasing well-being and quality of life. Physical activity (PA) performed outdoors has been found to be particularly good for promoting well-being. However, participation in PA can change during the course of a lifetime. Parenthood has been found to be a life event associated with decreased PA, especially among women, although studies in the field are sparse. The aim of this study was to investigate participation in outdoor recreational PA, and factors influencing participation among parents-to-be, with and without previous children, from a gender perspective. Methods: This study included baseline data from parents-to-be, 224 women and 208 men, from the municipality of Karlskrona in south-east Sweden. Data collection was carried out during 2008-2009. We measured the self-reported amount of outdoor recreational PA undertaken during the last year and analysed the probability of participating in this PA using 25 variables covering individual and socioeconomic factors. Results: Seventy-six per cent of the women and 65% of the men had participated in outdoor recreational PA, varying from several times per month to every day, over a 12-month period prior to one month before pregnancy. Participation in PA indoors and owning a dog or a horse emerged as the most important factors associated with the probability of participation in outdoor recreational PA. Men were affected by a greater number of factors than women, for example men who had a family situation that permitted outdoor recreational PA participated in activities to a greater extent than men without such a family situation. The physical aspect, i.e. improved physical condition, staying power and vigour, also played a significant role with regard to participation among men. Conclusions: Becoming a parent is a life-changing event that affects participation in PA. By offering family-oriented PA choices that involve both parents and children, midwives and health promoters can encourage parents to be active and to support each other. The promotion of outdoor recreational PA, which also has restorative effects on well-being, needs to focus on activities which are attractive and affordable for the majority of both women and men

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

Associations between psychological intervention for anxiety disorders and risk of dementia: a prospective cohort study using national health-care records data in England.

BACKGROUND: Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. METHODS: In this prospective cohort study, data from nationally provided psychological therapy services in England termed Improving Access to Psychological Therapies from 2012 to 2019 were linked to medical records, including dementia diagnoses as defined by the tenth edition of the International Classification of Diseases, up to 8 follow-up years later. Inclusion criteria were as follows: (1) patients who were aged 65 years and older; (2) patients with a probable anxiety disorder; and (3) those with no previous or current diagnosis of dementia. Cox proportional hazards models were constructed to test whether reliable improvement in anxiety following psychological intervention was associated with future dementia incidence. The primary outcome was all-cause dementia and cases were identified using ICD-10 dementia codes from Hospital Episode Statistics, Mental Health Services Dataset, and mortality data. For main analyses, hazards ratios (HRs) are presented. FINDINGS: Data from 128 077 people aged 65 years and older attending a nationally provided psychological intervention service in England were linked to medical records. 88 019 (69·0%) of 127 064 participants with available gender data were women and 39 585 (31·0%) were men. 111 225 (95·9%) of 115 989 with available ethnicity data were of White ethnicity. The mean age of the sample was 71·55 years (SD 5·69). Fully adjusted models included data from 111 958 people after 16 119 were excluded due to missing data on key variables or covariates. 4510 (4·0%) of 111 958 participants had a dementia diagnosis. The remaining 107 448 (96·0%) were censored either at date of death or when the final follow-up period available for analyses was reached. People who showed reliable improvement in anxiety had lower rates of later dementia diagnosis (3·9%) than those who did not show reliable improvement (5·1%). Reliable improvement in anxiety following psychological intervention was associated with reduced incidence of all-cause dementia (HR 0·83 [95% CI 0·78-0·88]), Alzheimer's disease (HR 0·85 [0·77-0·94]), and vascular dementia (HR 0·80 [0·71-0·90]). Effects did not differ depending on anxiety disorder diagnosis. INTERPRETATION: Results showed that reliable improvement in anxiety from psychological therapy was associated with reduced incidence of future dementia. There are multiple plausible explanations for this finding and further research is needed to distinguish between these possibilities. Missing data in the sample limit reliability of findings. FUNDING: Alzheimer's Society, Medical Research Council, Wellcome Trust, and UCLH National Institute for Health and Care Research Biomedical Research Centre