Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

The impact of care pathways for exacerbation of Chronic Obstructive Pulmonary Disease: rationale and design of a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hospital treatment of chronic obstructive pulmonary disease (COPD) frequently does not follow published evidences. This lack of adherence can contribute to the high morbidity, mortality and readmissions rates. The European Quality of Care Pathway (EQCP) study on acute exacerbations of COPD (NTC00962468) is undertaken to determine how care pathways (CP) as complex intervention for hospital treatment of COPD affects care variability, adherence to evidence based key interventions and clinical outcomes.</p> <p>Methods</p> <p>An international cluster Randomized Controlled Trial (cRCT) will be performed in Belgium, Italy, Ireland and Portugal. Based on the power analysis, a sample of 40 hospital teams and 398 patients will be included in the study. In the control arm of the study, usual care will be provided. The experimental teams will implement a CP as complex intervention which will include three active components: a formative evaluation of the quality and organization of care, a set of evidence based key interventions, and support on the development and implementation of the CP. The main outcome will be six-month readmission rate. As a secondary endpoint a set of clinical outcome and performance indicators (including care process evaluation and team functioning indicators) will be measured in both groups.</p> <p>Discussion</p> <p>The EQCP study is the first international cRCT on care pathways. The design of the EQCP project is both a research study and a quality improvement project and will include a realistic evaluation framework including process analysis to further understand why and when CP can really work.</p> <p>Trial Registration number</p> <p><b>NCT00962468</b></p

Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels

Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically

Phylogenomic analysis of the Chlamydomonas genome unmasks proteins potentially involved in photosynthetic function and regulation

Chlamydomonas reinhardtii, a unicellular green alga, has been exploited as a reference organism for identifying proteins and activities associated with the photosynthetic apparatus and the functioning of chloroplasts. Recently, the full genome sequence of Chlamydomonas was generated and a set of gene models, representing all genes on the genome, was developed. Using these gene models, and gene models developed for the genomes of other organisms, a phylogenomic, comparative analysis was performed to identify proteins encoded on the Chlamydomonas genome which were likely involved in chloroplast functions (or specifically associated with the green algal lineage); this set of proteins has been designated the GreenCut. Further analyses of those GreenCut proteins with uncharacterized functions and the generation of mutant strains aberrant for these proteins are beginning to unmask new layers of functionality/regulation that are integrated into the workings of the photosynthetic apparatus

Nasal symptoms, epithelial injury and neurogenic inflammation in elite swimmers

A high burden of lower airway symptoms is found in elite swimmers. To what extent elite swimmers suffer from upper airway symptoms and how these associate with nasal inflammation is less clear. We here aimed to evaluate upper airway symptoms and nasal inflammation in elite athletes.status: publishe