Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease.

BACKGROUND: Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. METHODS: Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. RESULTS: A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. CONCLUSION: The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage. Some of these particular up-regulated and down-regulated genes are related to inflammatory processes and could be considered as biomarker candidates for disease progression in subjects at risk to develop RA.

Fertilization and connectivity in the Garrucha Canyon (SE-Spain) implications for Marine Spatial Planning.

Marine Spatial Planning is usually based on benthic georeferenced information or GPS tracked human activities, whereas the pelagic ecosystem is often ignored because of scarce and limited surface information. However, the 3-D pelagic ecosystem plays a key role connecting all the other ecosystems by physical (currents) and biological (migration) processes. According to remote sensing the Garrucha Canyon is oligotrophic, but 3-D sampling reveals subsurface upwelling, and converts it into the richest area around the Cape of Gata. Vertical connectivity by means of zooplankton migration, measured at two sampling stations, is 40 and 220 times faster than microphytoplankton settling and vertical water velocities respectively. Thus coupled physical-biological connectivity models are necessary to estimate the ecosystem connection and the fate of carbon, but also other substances (e.g. radioactivity), that might accumulate throughout the food-web. This is especially important in the Garrucha Canyon and the Coastal Areas Management Programme Levante de Almería where natural heritage and extractive fishery are important for the local economy.

Angiomatosis leptomeníngea temporo-occipital de diagnóstico en edad adulta / Adult diagnosis of temporo-occipital leptomeningeal angiomatosis

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Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinically isolated syndromes.

BACKGROUND: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS. METHODS: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof-Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0. RESULTS: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof-Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%. CONCLUSION: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.

Hematoma intracerebral agudo isodenso / Isodense acute intracranial haematoma

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