Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina

<p>Abstract</p> <p>Background</p> <p>Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA).</p> <p>Methods</p> <p>From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10⁸± 4.3*10⁸mononuclear and 1.65*10⁷± 1.42*10⁷CD34⁺cells by PRCSP..</p> <p>Results</p> <p>ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019).</p> <p>Conclusions</p> <p>PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.</p

A fast refill of the Mediterranean after the Messinian salinity crisis? Looking for independent evidence

One of the main competing scenarios proposed for the termination of the Messinian salinity crisis consists of a geologically-rapid refill of the Mediterranean after a km-scale drawdown of the Mediterranean Sea level. The main evidence supporting this Zanclean Flood scenario is a nearly 400 km long and several hundred meters deep erosion channel across the Strait of Gibraltar. This erosion channel extends from the Gulf of Cadiz to the Algerian Basin and implies the excavation of ca. 1000 km3 of Miocene sediment and older bedrock. However, additional evidence supporting this catastrophic flood hypothesis is missing, other than the fast transition from MSC deposits to open-marine facies. Here we test two consequences that an outburst flood of the Mediterranean should imply: First, an excavated channel similar to the one across the Gibraltar Strait should be present in the old sill separating the east and west Mediterranean domains (none has been yet reported). A second smoking gun would be finding the present emplacement of the materials eroded during the Zanclean flood (but quantitative predictions of where to look for them are still missing).peer-reviewe

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. Methods: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. Results: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. Conclusions: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression

Influence of alongslope processes on modern turbidite systems and canyons in the Alboran Sea (southwestern Mediterranean)

International audienceThis is an interdisciplinary study that combines morphoseismics, sedimentology and numerical modelling to elucidate at different scales of resolution the influence of alongslope processes on the turbidite systems (TSs) and canyons in the Alboran Sea (southwestern Mediterranean). Nine TSs are mapped in the Spanish margin (La Linea, Guadiaro, Baños, Torrenueva, Fuengirola, Salobreña, Sacratif, Calahonda and Almeria) and two in the Alboran Ridge (Piedra Escuela and Al-Borani). In the Moroccan margin, there are only two canyons (Ceuta and Nekor). Distinctive morphoseismic and sedimentological signatures from TSs and canyons have enabled three regional models of alongslope influence to be distinguished: a) Alongslope processes are dominant. This scenario characterizes the canyons of the Moroccan margin. The diagnostic signature is the lack of leveed channels and lobes at the Ceuta and Nekor Canyon mouths. b) Different degrees of interplay exist between alongslope and downslope processes. This scenario occurs in the TSs of the western Spanish margin. Here, the alongslope influence on TSs (La Linea, Guadiaro, Baños, Torrenueva and Fuengirola) is evidenced by the lack of overbank deposits in the La Linea and Guadiaro Canyons and an alongslope trend in the morpho-architecture of the channelized lobes and in the textural distribution of canyon/channel deposits (mass-flow deposits and turbidites). Both signatures indicate sandier TSs as well as Bouma turbidite sequences lacking the finest levels towards the Strait of Gibraltar. Local intercalations of contourites are also present in the Guadiaro lobe deposits. c) Downslope processes are dominant. This scenario characterizes the TSs of the eastern and central Spanish margin and Alboran Ridge. There, TSs seem to be controlled solely by the characteristics of the downslope gravity flows that transport sediment. The hydrodynamic and sediment dispersion models confirm that the main oceanographic factors governing the variable alongslope influence in TSs and canyons are the following: a vigorous WMDW flow along the Moroccan margin and the energetic Atlantic Jet, western Atlantic anticyclonic gyre and general acceleration of the Mediterranean waters towards the Strait of Gibraltar, along the western Spanish margin. This study demonstrates the pivotal role that alongslope processes can play in the onset and formation of TSs and canyons at continental margins

Near-tetraploid cancer cells show chromosome instability triggered by replication stress and exhibit enhanced invasiveness.

A considerable proportion of tumors exhibit aneuploid karyotypes, likely resulting from the progressive loss of chromosomes after whole-genome duplication. Here, by using isogenic diploid and near-tetraploid (4N) single-cell-derived clones from the same parental cell lines, we aimed at exploring how polyploidization affects cellular functions and how tetraploidy generates chromosome instability. Gene expression profiling in 4N clones revealed a significant enrichment of transcripts involved in cell cycle and DNA replication. Increased levels of replication stress in 4N cells resulted in DNA damage, impaired proliferation caused by a cell cycle delay during S phase, and higher sensitivity to S phase checkpoint inhibitors. In fact, increased levels of replication stress were also observed in nontransformed, proliferative posttetraploid RPE1 cells. Additionally, replication stress promoted higher levels of intercellular genomic heterogeneity and ongoing genomic instability, which could be explained by high rates of mitotic defects, and was alleviated by the supplementation of exogenous nucleosides. Finally, our data found that 4N cancer cells displayed increased migratory and invasive capacity, both in vitro and in primary colorectal tumors, indicating that tetraploidy can promote aggressive cancer cell behavior.-Wangsa, D., Quintanilla, I., Torabi, K., Vila-Casadesus, M., Ercilla, A., Klus, G., Yuce, Z., Galofre, C., Cuatrecasas, M., Lozano, J. J., Agell, N., Cimini, D., Castells, A., Ried, T., Camps, J. Near-tetraploid cancer cells show chromosome instability triggered by replication stress and exhibit enhanced invasiveness

Clustered carbonate mounds in the upper continental slope of the Alboran Sea

IX Simpósio sobre a Margem Ibérica Atlântica (MIA 2018) - IX Simposio sobre el Margen Ibérico Atlántico - IX Symposium on the Iberian Atlantic Margin, 4-7 September de 2018, Coimbra.-- 2 pages, 1 figureHigh-resolution multibeam bathymetry, seismic reflection data and underwater imagery were used to characterize the morphostructure as well as the ancient and contemporary habitat-forming species in three fields of clustered mounds that were recently discovered in the northern Alboran Sea. A total of 150 small mounds were detected between 140 to 300 m water depth. They display reliefs ranging from 2 to 17 m and circular or mainly NW-SE elongated shapes. The seismic reflection data highlight the presence of stacked buried and exposed mounds that exhibit acoustically transparent facies. They have an heterogeneous composition, mainly consisting of bioclasts of solitary scleractinians, bivalves and rhodoliths that are covered with soft sediments. These mounds may have gone through a complex mound development with a further geological and biological evolution in interaction with bottom currents. The analysis of these carbonate mounds may shed new light on the enormous scale of carbonate deposition along the Iberian Mediterranean marginThis work is a contribution to MONCARAL, funded by the Instituto Español de Oceanografia and FAUCES (CMT2015-65461-C2-R/MINECO/FEDER) projectsPeer Reviewe

Morphostructure of three carbonate mounds fields in the upper continental slope of the Alboran Sea

34th International Association of Sedimentologists (IAS) Meeting of Sedimentology, Sedimentology to face societal challenges on risk, resources and record of the past, 10-13 September 2019, Rom

Morphostructure of three carbonate mounds fields in the upper continental slope of the Alboran Sea

34th International Association of Sedimentologists (IAS) Meeting of Sedimentology, Sedimentology to face societal challenges on risk, resources and record of the past, 10-13 September 2019, Rom