Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians

Background/aims To investigate ethnic differences in retinal vascular function and their relationship to traditional risk indicators for cardiovascular disease (CVD). Methods A total of 90 normoglycaemic subjects (45 South Asian (SA) and 45 age- and gender-matched white Europeans (WEs)) were recruited for the present study. Retinal vessel reactivity to flickering light was assessed by means of the dynamic retinal vessel analyser according to a modified protocol. Fasting plasma glucose, triglycerides (TG), total, LDL and HDL cholesterol were also measured in all individuals. Results SA individuals showed higher fasting triglyceride (p=0.001) and lower HDL levels (p=0.007), leading to a higher TG:HDL-C ratio (p=0.001) than age-matched WE subjects. Additionally, in SAs, the retinal arterial reaction time in response to flicker stimulation was significantly longer in the last flicker cycle than in the WEs (p=0.039), and this change correlated positively with measured plasma TG levels (r=0.60; p=0.01). No such relationship was observed in the WEs (p>0.05). Conclusion Even in the absence of overt vascular disease, in otherwise healthy SAs there are potential signs of retinal vascular function impairment that correlates with established plasma markers for CVD risk.

Anticholinergic medication use and cognitive impairment in the older population:the Medical Research Council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=-0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.

The slope of the psychometric function and non-stationarity of thresholds in spatiotemporal contrast vision

The slope of the two-interval, forced-choice psychometric function (e.g. the Weibull parameter, ß) provides valuable information about the relationship between contrast sensitivity and signal strength. However, little is known about how or whether ß varies with stimulus parameters such as spatiotemporal frequency and stimulus size and shape. A second unresolved issue concerns the best way to estimate the slope of the psychometric function. For example, if an observer is non-stationary (e.g. their threshold drifts between experimental sessions), ß will be underestimated if curve fitting is performed after collapsing the data across experimental sessions. We measured psychometric functions for 2 experienced observers for 14 different spatiotemporal configurations of pulsed or flickering grating patches and bars on each of 8 days. We found ß ˜ 3 to be fairly constant across almost all conditions, consistent with a fixed nonlinear contrast transducer and/or a constant level of intrinsic stimulus uncertainty (e.g. a square law transducer and a low level of intrinsic uncertainty). Our analysis showed that estimating a single ß from results averaged over several experimental sessions was slightly more accurate than averaging multiple estimates from several experimental sessions. However, the small levels of non-stationarity (SD ˜ 0.8 dB) meant that the difference between the estimates was, in practice, negligible.

Executive function and emotional focus in autobiographical memory specificity in older adults

The current study examined the role of executive function in retrieval of specific autobiographical memories in older adults with regard to control of emotion during retrieval. Older and younger adults retrieved memories of specific events in response to emotionally positive, negative and neutral word cues. Contributions of inhibitory and updating elements of executive function to variance in autobiographical specificity were assessed to determine processes involved in the commonly found age-related reduction in specificity. A negative relationship between age and specificity was only found in retrieval to neutral cues. Alternative explanations of this age preservation of specificity of emotional recall are explored, within the context of control of emotion in the self-memory system and preserved emotional processing and positivity effect in older adults. The pattern of relationships suggests updating, rather than inhibition as the source of age-related reduction in specificity, but that emotional processing (particularly of positively valenced memories) is not influenced by age-related variance in executive control. The tendency of older adults to focus on positive material may thus act as a buffer against detrimental effects of reduced executive function capacity on autobiographical retrieval, representing a possible target for interventions to improve specificity of autobiographical memory retrieval in older adults.

Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis

Background - The negative feedback system is an important physiological regulatory mechanism controlling angiogenesis. Soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), acts as a potent endogenous soluble inhibitor of VEGF- and placenta growth factor (PlGF)-mediated biological function and can also form dominant-negative complexes with competent full-length VEGF receptors. Methods and results - Systemic overexpression of VEGF-A in mice resulted in significantly elevated circulating sFlt-1. In addition, stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF-A, induced a five-fold increase in sFlt-1 mRNA, a time-dependent significant increase in the release of sFlt-1 into the culture medium and activation of the flt-1 gene promoter. This response was dependent on VEGF receptor-2 (VEGFR-2) and phosphoinositide-3'-kinase signalling. siRNA-mediated knockdown of sFlt-1 in HUVEC stimulated the activation of endothelial nitric oxide synthase, increased basal and VEGF-induced cell migration and enhanced endothelial tube formation on growth factor reduced Matrigel. In contrast, adenoviral overexpression of sFlt-1 suppressed phosphorylation of VEGFR-2 at tyrosine 951 and ERK-1/-2 MAPK and reduced HUVEC proliferation. Preeclampsia is associated with elevated placental and systemic sFlt-1. Phosphorylation of VEGFR-2 tyrosine 951 was greatly reduced in placenta from preeclamptic patients compared to gestationally-matched normal placenta. Conclusion - These results show that endothelial sFlt-1 expression is regulated by VEGF and acts as an autocrine regulator of endothelial cell function.

Acute and long-term effects of peroxisome proliferator-activated receptor-γ activation on the function and insulin secretory responsiveness of clonal beta-cells

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2-100 M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 M) enhanced (p

Role, function and responsibilities of the safety practitioner in the United Kingdom

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Effects of short-term detraining on postprandial metabolism, endothelial function, and inflammation in endurance-trained men:dissociation between changes in triglyceride metabolism and endothelial function

Endurance-trained athletes experience a low level of postprandial lipaemia, but this rapidly increases with detraining. We sought to determine whether detraining-induced changes to postprandial metabolism influenced endothelial function and inflammation. Eight endurance-trained men each undertook two oral fat tolerance tests [blood taken fasted and for 6 h following a high-fat test meal (80 g fat, 80 g carbohydrate)]: one during a period of their normal training (trained) and one after 1 wk of no exercise (detrained). Endothelial function in the cutaneous microcirculation was assessed using laser Doppler imaging with iontophoresis in the fasted state and 4 h postprandially during each test. Fasting plasma triglyceride (TG) concentrations increased by 35% with detraining (P = 0.002), as did postprandial plasma (by 53%, P = 0.002), chylomicron (by 68%, P = 0.02) and very low-density lipoprotein (by 51%, P = 0.005) TG concentrations. Endothelial function decreased postprandially in both the trained (by 17%, P = 0.03) and detrained (by 22%, P = 0.03) conditions but did not differ significantly between the trained and detrained conditions in either the fasted or the postprandial states. These results suggest that, although fat ingestion induces endothelial dysfunction, interventions that alter postprandial TG metabolism will not necessarily concomitantly influence endothelial function.

Data Assimilation Technique For Flood Monitoring and Prediction

This paper focuses on the development of methods and cascade of models for flood monitoring and forecasting and its implementation in Grid environment. The processing of satellite data for flood extent mapping is done using neural networks. For flood forecasting we use cascade of models: regional numerical weather prediction (NWP) model, hydrological model and hydraulic model. Implementation of developed methods and models in the Grid infrastructure and related projects are discussed.

On the Mellin Transforms of Dirac’S Delta Function, The Hausdorff Dimension Function, and The Theorem by Mellin

Mathematics Subject Classification: 44A05, 46F12, 28A78

Generalization of the Modified Bessel Function and Its Generating Function

2000 Mathematics Subject Classification: 33C10, 33-02, 60K25

On the Generalized Confluent Hypergeometric Function and Its Application

2000 Mathematics Subject Classification: 26A33, 33C20

Arthur Lindo Patterson, his function and element preferences in early crystal structures

In 1934, Arthur Lindo Patterson showed that a map of interatomic vectors is obtainable from measured X-ray diffraction data without phase information. Such maps were interpretable for simple crystal structures, but proliferation and overlapping of peaks caused confusion as the number of atoms increased. Since the peak height of a vector between two particular atoms is related to the product of their atomic numbers, a complicated structure could effectively be reduced to a simple one by including just a few heavy atoms (of high atomic number) since their interatomic vectors would stand out from the general clutter. Once located, these atoms provide approximate phases for Fourier syntheses that reveal the locations of additional atoms. Surveys of small-molecule structures in the Cambridge Structural Database during the periods 1936-1969, when Patterson methods were commonly used, and 1980-2013, dominated by direct methods, demonstrate large differences in the abundance of certain elements. The moderately heavy elements K, Rb, As and Br are the heaviest elements in the structure more than 3 times as often in the early period than in the recent period. Examples are given of three triumphs of the heavy atom method and two initial failures that had to be overcome. © 2014 © 2014 Taylor & Francis.