Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Analysis of proliferative activity in oral gingival epithelium in immunosuppressive medication induced gingival overgrowth

BACKGROUND: Drug-induced gingival overgrowth is a frequent adverse effect associated principally with administration of the immunosuppressive drug cyclosporin A and also certain antiepileptic and antihypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and accumulation of excessive amounts of connective tissue. The mechanism by which the drugs cause gingival overgrowth is not yet understood. The purpose of this study was to compare proliferative activity of normal human gingiva and in cyclosporine A-induced gingival overgrowth. METHODS: Gingival samples were collected from 12 generally healthy individuals and 22 Cyclosporin A-medicated renal transplant recipients. Expression of proliferating cell nuclear antigen was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and a monoclonal antibody for this antigen. RESULTS: There were differences between the Cyclosporin A group and control group in regard to proliferating cell nuclear antigen and epithelial thickness. In addition, the degree of stromal inflammation was higher in the Cyclosporin A group when compared with the control group. CONCLUSION: The results suggest that the increased epithelial thickness observed in Cyclosporin A-induced gingival overgrowth is associated with increased proliferative activity in keratinocytes

Humoral immune response to MUC5AC in patients with colorectal polyps and colorectal carcinoma

BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by colorectal polyps and carcinoma. It has been hypothesized that aberrant expression of MUC5AC in colorectal carcinoma tissues increased the overall survival of patients with colorectal carcinoma. The present study investigates the incidence of naturally occurring MUC5AC antibodies in the sera of normal individuals, patients with colonic polyps and patients with advanced colorectal carcinoma. A second aim was to determine the relationship of MUC5AC antibody with the prognosis of colorectal carcinoma. METHODS: Free circulating MUC5AC antibodies were measured using an enzyme-linked immunosorbent assay with a synthetic peptide corresponding to an 8 aa. segment of MUC5AC tandem repeat region. Immunohistochemical analysis was completed to demonstrate MUC5AC expression in the polyp specimens. RESULTS: MUC5AC antibodies were detected in 6 of 22 (27.3%) healthy subjects, 9 of 20 (45%) polyp patients, 18 of 30 (60%) patients with colorectal cancer. The presence of circulating free MUC5AC antibody levels was significantly correlated with expression of MUC5AC in polyp sections. Serum MUC5AC antibody positivity was higher in patients with colon located tumors, advanced stage and poorly differentiated tumors were found negatively affecting patient survival in our study. MUC5AC antibody positivity was higher in patients with poor prognostic parameters. Disease free survival and overall survival were shorter in this group of patients. In the multivariate analysis MUC5AC antibody positivity didn't find an independent prognostic factor on prognosis. CONCLUSION: Decreased survival in colorectal carcinoma patients with MUC5AC antibody positivity may be due to a decrease in the MUC5AC expression in tumor tissues of surviving carcinoma patients

Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure.</p> <p>Methods</p> <p>A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay.</p> <p>Discussion</p> <p>The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure.</p> <p>Trial Registration</p> <p>Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01143909">NCT01143909</a></p