A new computational framework for electro-activation in cardiac mechanics

This paper presents a novel computational framework for the numerical simulation of the electromechanical response of the myocardium during the cardiac cycle. The paper presents the following main novelties. (1) Two new mixed formulations, tailor-made for active stress and active strain coupling approaches, have been developed and used in conjunction with two different ionic models, namely Bueno-Orovio [1] and Ten Tusscher [2]. Taking as a reference the mixed formulations introduced by Bonet et al. [3] in the context of nonlinear elasticity, the proposed formulations include as unknown fields the geometry and the transmembrane potential (and possibly a Lagrange multiplier enforcing weakly the incompressibility constraint) as well as the deformation gradient tensor, its cofactor, its determinant, the gradient of the transmembrane potential and their respective work conjugates. The Finite Element implementation of these formulations is shown in this paper, where a static condensation procedure is presented in order to yield an extremely competitive computational approach. (2) A comprehensive and rigorous study of different ionic models (i.e Bueno-Orovio and Ten Tusscher) and electromechanical activation couplings (i.e active strain and active stress) has been carried out. (3) An analytical and numerical analysis of the possible loss of ellipticity and polyconvexity of one of the most widely used constitutive models in the context of cardiac mechanics is carried out in this paper, putting forward possible polyconvexifications of the existing model. (4) In addition, an invariant representation of Guccione's constitutive model is proposed. Finally, a series of numerical examples are included in order to demonstrate the applicability and robustness of the proposed formulations

Fluid flow in the subduction channel: Tremolite veins and associated blackwalls in antigoritite (Villa Clara serpentinite mélange, Cuba)

Exotic blocks of massive antigorite-serpentinite (antigoritite) document a deep-seated subduction channel in the Villa Clara serpentinite-matrix mélange, central Cuba. The petrological and geochemical characteristics of antigoritite allow distinguishing two types of rock: i) antigoritite and ii) dolomite-bearing antigoritite. Both types are intimately related in field exposures and represent deep peridotite infiltrated by H2O-CO2 fluid mixtures that triggered antigoritization and local carbonation. Fluid infiltration continued after antigoritization forming a vein network as a potential response to hydrofracturing that precipitated tremolitite in the veins and triggered fluid-antigoritite reaction forming blackwalls. The mineralogical and chemical zoning in the blackwalls (Atg + Chl + Tr adjacent to antigoritite and Chl + Tr adjacent to the tremolitite vein) attest for multi-step metasomatic processes during fluid-rock interaction characterized by advection of infiltrating fluid towards the blackwall and, possibly, by diffusion out of the blackwall towards the fluid-filled vein. Tentative thermodynamic modeling of the blackwall domain Atg + Chl + Tr points vein network formation at 400–500 °C and 5–10 kbar during exhumation in the subduction channel, suggesting the infiltration of deep-seated pressurized fluid that triggered hydrofracturing. The chemical compositions of antigoritites, veins and blackwalls indicate a LILE- and LREE-enriched fluid evolved from the subducting plate, while Srsingle bondNd isotope systematics are compatible with an external fluid composed of a mixture of fluids evolved from sediments and, probably to a lesser extent, altered oceanic crust.This research was funded by projects MICINN PID2019-105625RB-C21 (co-funded by Fondo Europeo de Desarrollo Regional, FEDER), Junta de Andalucía P20_00550, Catalonian project SGR 2014-1661 and the University of Granada. LD acknowledges PhD grant BES-2013-063205 of the Spanish Ministry of Economy and Competitiveness and scholarship of Fundació Universitària Agustí Pedro i Pons. Funding for open access charge: Universidad de Granada / CBUA

A comparison of Clinical Risk Index for babies (CRIB-II), Score for Neonatal Acute Physiology (SNAP-II) and SNAPPE-II in predicting parenteral nutrition necessity in low birth weight preterm neonates.

Advances in perinatal care have made it possible to improve survival of low birth weight neonates. Clinical risk index for babies (CRIB-II), score for neonatal acute physiology (SNAP-II), and SNAP-perinatal extension-II (SNAPPE-II) have been used as mortality predictors for preterm infants. Feeding intolerance is very frequent in preterm neonates, and the development of an early effective biomarker for its prediction could be useful for carrying out a proper feeding strategy. Our aim was to compare the ability of CRIB-II, SNAP-II and SNAPPE-II in predict the feeding intolerance and parenteral nutrition necessity in preterm neonates. Methods: A retrospective cohort study on preterm neonates’ born at Jaen Hospital Complex with low birth weight and ≤ 36 weeks of gestation was done. Epidemiological, clinical and clinical scores CRIB II, SNAP-II and SNAPPE-II were recorded. Results: 255 low birth weight preterm neonates, 131 males (51.4%), aged ≤32 weeks of gestation (71%), were enrolled at our hospital. Parenteral nutrition needed were significantly higher in preterm neonates weighed 2500-1500 g (73.3%) and ≤ 1000g (87%). CRIB-II, SNAP-II and SNAPPE-II mean values were higher in neonates group subjected to parenteral nutrition compared with oral nutrition (p<0.05). CRIB-II and SNAPPE-II scores significantly correlated with parenteral nutrition days (p<0.05). Overall mortality rate was 11%. The 78.6% of all deceased infants needed parenteral nutrition. Conclusion: Clinical Risk Index for babies (CRIB-II) better than SNAPPE-II correlated with the feeding intolerance and thus the parenteral nutrition days in preterm neonates with low birth weight.Subvencionado: Ayuda del Plan Propio de Investigación de la UMA. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Oracion fúnebre que en las solemnes exequias del Ilmo. Sr. D. Vicente Roman y Linares Obispo de Dan-Sara ...

Adorno xil. al principio del text

Electron-scattering cross sections for collisions with tetrahydrofuran from 50 to 5000 eV

In this paper, we report on total electron tetrahydrofuran (C4H8O) scattering cross-section measurements for energies in the range from 50 to 5000 eV with experimental errors of about 5%. In addition, integral elastic and inelastic cross sections have been calculated over a broad energy range (1–10 000 eV), with an optical potential method assuming a screening-corrected independent atom representation. Partial and total ionization cross sections have been also obtained by combining simultaneous electron and ion measurements with a time-of-flight analysis of the ionic induced fragmentation. Finally, an average energy distribution of secondary electrons has been derived from these measurements in order to provide data for modeling electron-induced damage in biomolecular systems

The extracellular proteins of Lactobacillus acidophilus DSM 20079T display anti-inflammatory effect in both in piglets, healthy human donors and Crohn’s Disease patients

Lactobacillus genus includes both probiotic and representative strains of the human gut microbiota. Independent studies have reported on the anti-inflammatory properties of different Lactobacillus strains, although we are far from understanding the underlying molecular interplay. In this work we show that a daily administration of Lactobacillus acidophilus DSM20079T (DSM20079) to healthy piglets resulted in plasmatic increases of the anti-inflammatory IL10, whilst IL12 and the pro-inflammatory ratio IL12+TNFα/IL10 decreased. The extracellular protein fraction of DSM20079 was identified as the responsible for the crosstalk interaction that elicited these tolerogenic effects. This strain was able to activate innate immune pathways in dendritic cells and to decrease the production of pro-inflammatory cytokines in both CD4+/CD8+ T cell subsets in healthy donors and in Crohn’s Disease patients. The tolerogenic effect exerted by the extracellular proteins of this strain suggests their potential use as coadjutant for therapeutic applications targeting chronic inflammatory illnesses.Asociación Española Contra el Cancer | Ref. PS-2016Fundação para a Ciência e a Tecnologia | | Ref. UID/BIO/04469/2013Agencia Estatal de Investigación | Ref. AGL2016-78311-RPrincipado de Asturias | Ref. PCTI 2018–2020Xunta de Galicia | Ref. ED431C2018/5

Neutral evolution of drug resistant colorectal cancer cell populations is independent of their KRAS status

Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1) do mutations in the target/pathway confer resistance? (2) Are these mutations pre-existing? (3) What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC). We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g) and regression (d, decay) of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor) antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia

In silico and functional analyses of immunomodulatory peptides encrypted in the human gut metaproteome

This work supports the massive presence of potential immunomodulatory peptides in the human gut metaproteome. These peptides were identified through the MAHMI database as potentially anti-inflammatory, and sixteen of them synthesized for characterize their mechanism of action. From them, peptide HM14 was encrypted in an extracellular protein produced by Bifidobacterium longum, a common member of the human microbiota, and displayed the highest anti-inflammatory capability. Molecular mechanism of action of HM14 pointed to a specific interaction between this immunomodulatory peptide and antigen presenting cells, which resulted in a higher formation of iTreg cells. Moreover, HM14 was effective in decreasing pro-inflammatory parameters in PBMCs isolated from a cohort of Crohn's patients. Finally, non-targeted metabolomics confirmed the ability of HM14 to modulate the metabolic activity of PBMCs to fulfil its energy and biosynthetic requirements. Overall, our combined in silico/multiomics approach supports the human gut metaproteome as a source for immunomodulatory peptides.Ministerio de Economía y Competitividad | Ref. AGL2013-44761-PAgencia Estatal de Investigación | Ref. AGL2016-78311-