82 research outputs found

    The delirium and population health informatics cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population.

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    Background: Delirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline? Methods: The Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged ≥70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years. Discussion: DELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged ≥70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes

    Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis

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    To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L−1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (−4.14 [−8.17, −0.11] mg.L−1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (−0.30 [−3.67, 3.07] mg. L−1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn

    A PSTOL-like gene, TaPSTOL, controls a number of agronomically important traits in wheat

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    Background Phosphorus (P) is an essential macronutrient for plant growth, and is required in large quantities by elite varieties of crops to maintain yields. Approximately 70% of global cultivated land suffers from P deficiency, and it has recently been estimated that worldwide P resources will be exhausted by the end of this century, increasing the demand for crops more efficient in their P usage. A greater understanding of how plants are able to maintain yield with lower P inputs is, therefore, highly desirable to both breeders and farmers. Here, we clone the wheat (Triticum aestivum L.) homologue of the rice PSTOL gene (OsPSTOL), and characterize its role in phosphate nutrition plus other agronomically important traits. Results TaPSTOL is a single copy gene located on the short arm of chromosome 5A, encoding a putative kinase protein, and shares a high level of sequence similarity to OsPSTOL. We re-sequenced TaPSTOL from 24 different wheat accessions and (3) three T. durum varieties. No sequence differences were detected in 26 of the accessions, whereas two indels were identified in the promoter region of one of the durum wheats. We characterised the expression of TaPSTOL under different P concentrations and demonstrated that the promoter was induced in root tips and hairs under P limiting conditions. Overexpression and RNAi silencing of TaPSTOL in transgenic wheat lines showed that there was a significant effect upon root biomass, flowering time independent of P treatment, tiller number and seed yield, correlating with the expression of TaPSTOL. However this did not increase PUE as elevated P concentration in the grain did not correspond to increased yields. Conclusions Manipulation of TaPSTOL expression in wheat shows it is responsible for many of the previously described phenotypic advantages as OsPSTOL except yield. Furthermore, we show TaPSTOL contributes to additional agronomically important traits including flowering time and grain size. Analysis of TaPSTOL sequences from a broad selection of wheat varieties, encompassing 91% of the genetic diversity in UK bread wheat, showed that there is very little genetic variation in this gene, which would suggest that this locus may have been under high selection pressure

    Dysglycaemia and South Asian ethnicity: a proteomic discovery and confirmation analysis highlights differences in ZAG

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    Aims To (1) explore and verify differences in the plasma proteome of white European (WE) and South Asian (SA) adults with normal glycaemic control (NGC) or non-diabetic hyperglycaemia (NDH) and to (2) validate these findings using a separate WE and SA cohort at a high risk of NDH. Methods Mass spectrometry analysis was performed on fasted samples from 72 WE or SA men with NGC or NDH. These results were verified using specific biochemical assays and validated by repeating the analysis in an additional cohort of 30 WE and 30 SA adults. Proteomic results were analysed using independent samples t test and univariate analysis. The targeted assay results were analysed using generalised linear models with adjustment for appropriate covariates including age, BMI, fasting plasma glucose, high-density lipoprotein-cholesterol, triglycerides and sex. Results Only zinc-alpha-2-glycoprotein (ZAG) significantly differed between both ethnicities and glycaemic control groups. ZAG-specific biochemical assays verified the lower circulating ZAG in SAs (41.09 versus 37.07 (mg L−1); p = 0.014), but not the difference between NGC and NDH groups (p = 0.539). Validation of the ethnicity difference in a separate cohort confirmed that, after adjustment for covariates, ZAG was lower in SAs (p = 0.018). There was no association between ZAG and glycaemic control in the validation cohort. Conclusions Our analyses identified that ZAG is lower in SAs compared to WEs, but its difference between glycaemic control statuses was uncertain. Further research is needed to establish whether lower ZAG in SAs is associated with, or prognostic of, health outcomes, particularly regarding the risk of dysglycaemia
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