133 research outputs found

    A Role for Platelets in Normal Pregnancy

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    Using the theory of planned behaviour to explore the multicultural nursing workforces' behavioural intentions to comply with nursing policies and procedures in Prince Military Medical City (PSMMC) in Kingdom of Saudi Arabia

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    Background & aims: mBarrett's esophagus (BE) increases risk for esophageal adenocarcinoma (EAC). Increased risk for BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma in CRTC1 and BARX1, and within 100 kb FOXP1. We aimed to identify SNPs that increased risk for BE in a genome-wide association study (GWAS) and to validate previously reported associations.Methods: we performed a GWAS to identify variants associated with BE and further analyzed promising variants identified by the BEACON. We performed genotype analysis of 10,158 patients with BE and 21,062 controls.Results: we identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10?11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10?9). The closest protein-coding genes were GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. We also identified 3 SNPS already identified by the BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, near ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10?9).Conclusions: we identified 2 loci associated with risk for BE and provide data to support a locus previously associated with risk in the BEACON. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory respons

    Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case–control plasma proteomics study

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    Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case–control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann–Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE

    Urinary Procoagulant Activity in Health and Disease Method Development and Clinical Development

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    The broad aims of this thesis are to: 1) develop and validate a novel and reliable Urine Tissue Factor (uTF) assay, 2) study uTF function, expression and origin, 3) address factors which might affect uTF measurements in health and renal disorders, 4) re-assess the diagnostic value of uTF levels in cancer, glomerular injuries and inflammatory conditions, 5) examine the hypothesis that uTF levels reflect tumour taken by relating these to disease stage, tumour recurrence and conventional markers of tumour progression and 6) investigate whether uTF levels mirror those of blood mTF activation.Urine and/or blood samples were collected from a total of 1658 subjects covering normal individuals, patients with renal insufficiency, four types of malignant tumours and corresponding benign conditions and glomerulonephritis.The new uTF method is reproducible (intra-assay CV 2.3%, inter-assay CV 8.1%) with very low variation in normal controls and no significant diurnal or day-to-day variation once values were corrected for urine concentration. uTF was expressed on lipid vesicles which are essential for its activity. Cellular TF antigen was localised to the distal and proximal tubules, uTF was stable and levels were not significantly affected by glomerular permeability and filtration, tubular function nor by the presence of contaminants in urine. Patients with malignant tumours, glomerular injury and various inflammatory conditions have significantly higher uTF activity compared to normal subjects or patients with benign non-inflammatory disease. Levels were significantly associated with histological tumour grade, malignant recurrence and other markers of tumour aggressiveness.</p

    Tissue factor: biological function and clinical significance

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    Tissue Factor is the principal cellular initiator of normal blood coagulation. It is frequently encrypted in the plasma membrane of cells in contact with blood, but under certain pathological conditions endothelial cells, monocytes or macrophages may express tissue factor; and hence trigger coagulation activation. Aberrant expression of tissue factor by these cells is thought to be responsible for the thrombophilia found in septic shock, atherosclerosis and cancer. Tissue factor is produced by tumor-associated macrophages where it is believed to play an important role in tumor growth and dissemination. It may also be involved in other cellular processes such as intracellular signalling, angiogenesis and embryonic blood-vessel development. Tissue factor can be found both as free (soluble tissue factor) and membrane bound forms. Several studies have shown that measurements of any of these forms may provided clinically significant information, particularly in patients with malignant and inflammatory diseases, and are cost-effective

    Back to basics: histological, microbiological, and biochemical sampling in wound care

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    Despite the advances in our understanding of normal and abnormal wound healing over the past decade, a specific biomarker which can be used clinically to identify 'hard-to-heal' wounds still remains elusive. Tissue and exudate samples extracted from the site of the wound are traditionally analysed using histological, microbiological and biochemical laboratory techniques. The aim of this paper is to review the advantages of these techniques, their limitations and the rapid developments in the fields of microbiology and proteomics, which are offering new insights into the differences between healing and non-healing wounds
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