Shape Optimization of Slotted Steel Plate Dampers using the ‎Simulated Annealing Algorithm

This paper reports a procedure for maximizing the energy dissipation capacity (EDC) of a slotted steel plater damper by changing its initial geometrical shape. The methodology uses a simulated annealing algorithm to iteratively vary the slots' disposition, number, and geometry while improving the EDC. This capacity is computed for each tested configuration from a finite element analysis in ABAQUS, considering a cyclic displacement protocol. Five initial sections are enhanced, with the optimal one evoking a sand clock shape with two symmetric slots. The EDC increment is higher than 300%. It is observed that the objective function is multi-modal, and the optimal solution depends on the initial design. The proposed procedure is computationally easy to implement and requires less than fifty iterations to guarantee convergence in all cases

Antiagregantes y fractura de cadera

Fundamento y objetivo: El propósito de nuestro estudio ha sido comprobar si la terapia antiagregante de cualquier tipo, disminuye de forma significativa la mortalidad de los pacientes que sufren una fractura de cadera, en base a una reducción de la inflamación producida por la lesión. Pacientes y objetivo: Se ha realizado un estudio observacional, longitudinal y retrospectivo, en el que hemos incluido a todos los pacientes tratados en nuestro hospital en el año 2016. Se obtuvieron un total de 422 pacientes, que dividimos en dos grupos en función de si estuvieron o no antiagregados tras la fractura, para analizar su mortalidad intrahospitalaria, al mes, a los 12 meses y a los 40 meses. Resultados: El tratamiento con antiagregantes redujo la mortalidad de forma significativa en el mes tras la fractura (p=0.047), posteriormente, las diferencias no fueron significativas, con tendencia a igualarse entre las mortalidades de ambos grupos. Conclusiones: Creemos que la reducción de la mortalidad a corto plazo puede haberse producido por al efecto antiinflamatorio de los antiagregantes. Es necesario realizar un estudio más potente, que confirme nuestros resultados, y que nos permita conocer si estaría indicado tratar a todos los pacientes con fractura de cadera con antiagregantes.<br /

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

BACKGROUND In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES The authors aimed to determine the role of the calcineurin splicing variant CnA beta 1 in the context of cardiac hypertrophy and its mechanism of action. METHODS Transgenic mice overexpressing CnAb1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnA beta 1 (CnA beta 1(Delta i12) mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. RESULTS In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnA beta 1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAb1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnA beta 1. CnA beta 1(Delta i12) mice show increased cardiac hypertrophy and declined contractility. CONCLUSIONS The metabolic reprogramming induced by CnAb1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches. (J Am Coll Cardiol 2018; 71: 654-67) (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).This work was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-608027 to Dr. Lara-Pezzi; Meet-ITN-317433 to Dr. Enriquez; UE0/MCA1108 to Dr. Acin-Perez), from the Spanish Ministry of Economy and Competitiveness (SAF2015-65722-R and SAF2012-31451 to Dr. Lara-Pezzi; SAF2015-71521-REDC, BFU2013-50448, and SAF2012-32776 to Dr. Enriquez; RyC-2011-07826 to Dr. Acin-Perez; BIO2012-37926 and BIO2015-67580-P to Dr. Vazquez), from the Spanish Carlos III Institute of Health (CPII14/00027 to Dr. Lara-Pezzi; RD12/0042/066 to Drs. Garcia-Pavia and Lara-Pezzi), from the Regional Government of Madrid (2010-BMD-2321 ``Fibroteam´´ to Dr. Lara-Pezzi; 2011-BMD-2402 ``Mitolab´´ to Dr. Enriquez) and the FIS-ISCIII (PRB2-IPT13/0001 and RD12/0042/0056-RIC-RETICS to Dr. Vazquez). This work was also supported by the Plan Estatal de IthornDthornI 2013-2016-European Regional Development Fund (FEDER) ``A way of making Europe,´´ Spain. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Drs. Vazquez and Garcia-Pavia have served as consultants for VL39. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Padron-Barthe, Villalba-Orero, and Gomez-Salinero contributed equally to this work and are joint first authors. Robyn Shaw, MD, PhD, served as Guest Editor for this paper.S

Induction of the calcineurin variant CnAβ1 after myocardial infarction reduces post-infarction ventricular remodelling by promoting infarct vascularization

AIMS: Ventricular remodelling following myocardial infarction progressively leads to loss of contractile capacity and heart failure. Although calcineurin promotes maladaptive cardiac hypertrophy, we recently showed that the calcineurin splicing variant, CnAβ1, has beneficial effects on the infarcted heart. However, whether this variant limits necrosis or improves remodelling is still unknown, precluding translation to the clinical arena. Here, we explored the effects and therapeutic potential of CnAβ1 overexpression post-infarction. METHODS AND RESULTS: Double transgenic mice with inducible cardiomyocyte-specific overexpression of CnAβ1 underwent left coronary artery ligation followed by reperfusion. Echocardiographic analysis showed depressed cardiac function in all infarcted mice 3 days post-infarction. Induction of CnAβ1 overexpression 1 week after infarction improved function and reduced ventricular dilatation. CnAβ1-overexpressing mice showed shorter, thicker scars, and reduced infarct expansion, accompanied by reduced myocardial remodelling. CnAβ1 induced vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which resulted in increased infarct vascularization. This paracrine angiogenic effect of CnAβ1 was mediated by activation of the Akt/mammalian target of rapamycin pathway and VEGF. CONCLUSIONS: Our results indicate that CnAβ1 exerts beneficial effects on the infarcted heart by promoting infarct vascularization and preventing infarct expansion. These findings emphasize the translational potential of CnAβ1 for gene-based therapies.European Union [ERG-239158, CardioNeT-ITN-289600]; Spanish Ministry of Science and Innovation [BFU2009-10016, SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Fondo de Investigaciones Sanitarias [RD12/0042/0066]; Spanish Ministry of Economy and Competitiveness; Pro-CNIC FoundationS