Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Degradation of toxic piridinediols derived from mimosine by rumen bacteria: I. Microbiological aspects

La mimosina es un compuesto tóxico presente en la leguminosa tropical Leucaena leucocephala que limita el uso nutricional de esta planta en animales domésticos. Tanto animales monogástricos como rumiantes pueden intoxicarse con su consumo, pero algunos la toleran por poseer microorganismos ruminales que pueden degradar la mimosina y sus piridinedioles derivados 3,4- y 2,3-Dihidroxipiridina (3,4- y 2,3-DHP). En el presente trabajo se determinó la presencia de actividad degradadora del 2,3-DHP en cultivos bacterianos mixtos del rumen de animales consumiendo L. leucocephala en Venezuela y se caracterizó la degradación de este piridinediol por la bacteria ruminal Synergistes jonesii. Experimentos in vitro usando cultivos puros de S. jonesii indican que la degradación del 2,3-DHP ocurre al final de la fase logarítmica del crecimiento y además describe una cinética de degradación con una marcada inhibición por sustrato a altas concentraciones del piridinediol, sugiriendo que debe existir un umbral de concentración de enzimas que permita la degradación del 2,3-DHP del medio. S. jonesii es incapaz de degradar la mimosina, pero mostró actividad dagradadora contra los piridinedioles derivados 3,4-DHP y su isomero 2,3-DHP. El 3,4-DHP induce una actividad isomerasa que no está presente cuando el cultivo crece en presencia del 2,3-DHP, esta actividad es la responsable de la isomerización del 3,4-DHP en 2,3-DHP. Se demostró también que el sistema de degradación es inducible por sustrato, aunque la ausencia de sustrato puede causar la pérdida irreversible de la actividad degradadora. El 2,3-DHP se confirmó como sustrato intermediario en la degradación de piridinedioles pero también induce la expresión de enzimas degradadoras en la bacteria S. jonesii.222 - 232BimestralMimosine is a toxic compound presents in the tropical legume Leucaena leucocephala which restrict the nutritional use of this plant in domestic animals. Both monogastrics and ruminants could undergo toxicity consuming this plant. Soma ruminants can tolerate it because they have rumen microorganisms able to degrade mimosine and its pyridinediols derivatives: 3,4- y 2,3- Dihidroxypyridine (3,4- and 2,3-DHP). In the present study the existence of 2,3-DHP degrading-activity in mixed rumen bacterial cultures from cattle consuming L. leucocephala in Venezuela was determined, and the degradation of toxic pyridinediols by the rumen bacterium Synergistes jonesii was characterized. In vitro experiments using pure culture of S. jonesii indicated that the 2,3-DHP degradation was carried out at the end of the log-phase of bacterial growth and also the system showed substrato inhibition at high concentration of pyridinediols suggesting that a threshold of enzymes that allows 2,3-DHP-degradation from the medium is needed. S. jonesii is unable to degrade mimosine but it showed degrading activity against the mimosine derivatives 3,4-DHP and its isomer 2,3-DHP. 3,4-DHP induces an isomerase activity, which is lacking when the culture grows in 2,3-DHP. This latest activity is the responsible of the transformation of 3,4-DHP into 2,3-DHP. It, was also showed that the degradation is a substrate-induced enzymatic system. However, the lack of substrate might cause the irreversible lost of 2,3-DHP degrading-activity. 2,3-DHP .vas found as intermediary substrate and also induced the expression of degrading enzymes in S, jonesii

ASPECTOS BIOQUÍMICOS DE LA DEGRADACIÓN DE PIRIDINEDIOLES TÓXICOS DERIVADOS DE LA MIMOSINA POR LA BACTERIA RUMINAL SYNERGISTES JONESII

Synergistes jonesii es una bacteria anaer&oacute;bica aislada del rumen de animales resistentes a los efectos t&oacute;xicos de la leguminosa Leucaena leucoc&eacute;fala que exhibe actividad degradadora sobre piridinedioles t&oacute;xicos derivados de la mimosina. En el siguiente trabajo extractos proteicos libres de c&eacute;lulas de cultivos anaer&oacute;bicos de la bacteria S. jonesii fueron analizados para estudiar algunos aspectos bioqu&iacute;micos del metabolismo de las piridinas. Se demostr&oacute; que la actividad degradadora de piridinedioles se lleva a cabo en presencia de a-ceto-&aacute;cidos (piruvato o a-cetoglutarato) bajo una atm&oacute;sfera de nitr&oacute;geno, o bien en presencia de metil viologen solamente en presencia de hidr&oacute;geno. La degradaci&oacute;n de piridinedioles en presencia de metil viologen e hidr&oacute;geno se lleva a cabo gracias a la existencia de enzimas hidrogenasas en el extracto enzim&aacute;tico. El requerimiento de a-ceto-&aacute;cidos y agentes reductores de bajo potencial redox en atm&oacute;sfera anaer&oacute;bica (N2 o H2 respectivamente), indica que durante la degradaci&oacute;n del anillo de 2,3-dihidroxipiridina (2,3DHP) concurren reacciones de reducci&oacute;n enzim&aacute;tica. Entre los intermediarios evaluados el flav&iacute;n aden&iacute;n dinucle&oacute;tido (FAD) y la coenzima A (CoA) estimularon la actividad degradadora en el sistema a-ceto-&aacute;cido/N2 pero no estimularon la degradaci&oacute;n del 2,3DHP por s&iacute; solos. La carencia de amonio en los productos finales de la degradaci&oacute;n del anillo de piridina sugiere que alguno de los compuestos intermediarios de la degradaci&oacute;n debe ser nitrogenado. Mediante el an&aacute;lisis por HPLC y GC de muestras de c&eacute;lulas de S. jonesii resuspendidas en soluci&oacute;n buffer carbonato, suplementada con amonio, se determin&oacute; la presencia de ornitina y &aacute;cido propi&oacute;nico como posibles compuestos intermediarios del metabolismo del 2,3DHP.Biochemical Aspects of Mimosine-Derived Toxic Pyridinediols Degradation by the Rumen Bacterium Synergistes jonesiiABSTRACTSynergistes jonesii is an anaerobic bacterium isolated from the rumen of animals resistant to the toxic effect of the legume Leucaena leucocephala, which exhibits degrading activity on mimosinederived toxic pyridinediols. The following work reports analyses on cell-free protein extracts from anaerobic cultures of S. jonesii that were used to study some biochemical aspects of the metabolism of pyridinediols. It was demonstrated that the pyridinediol-degrading activity was carried out when either a-keto acids (pyruvic or a-keto-glutaric acid) were present in anaerobic condition or methyl viologen was present only under hydrogen atmosphere. Pyrideniols degradation occurred under hydrogen and methyl viologen due to the presence of hydrogenases in the cell-free extract. The requirement for a-keto acids and low redox potential reducing agents under anaerobic conditions (N2 or H2) indicate that reduction mechanisms are involved in the degradation of 2,3- dihydroxypyridine (2,3DHP). From the intermediary compounds tested flavin adenine dinucleotide (FAD) and coenzyme A (CoA) stimulated the degrading activity in a-keto acid/N2 system but failed to stimulate the 2,3DHP degradation by themselves. Lack of ammonium in the end products from degradation of the aromatic pyridine suggests that at least some of the intermediary products could be a nitrogencontaining compound. HPLC and GC analyses of samples taken from S. jonesii cells resuspended in carbonate buffered solution supplemented with ammonium showed the presence of ornitine and propionate as possible intermediary products of the 2,3DHP metabolism

Corrosion studies of PPy/Ni organic–inorganic hybrid bilayer coatings on commercial carbon steel

© 2014, Springer-Verlag Berlin Heidelberg. Electrodeposition of polypyrrole (PPy) was achieved on AISI 1018 carbon steel (CS) using a constant potential regime and cyclic voltammetry techniques evaluating different synthesis parameters, in monomer-containing oxalic acid solutions. Thereafter, CS PPy/Ni bilayer films were produced by Ni deposition onto PPy films using a potentiostatic method. The electrochemical performance of PPy/Ni-coated carbon steel systems was investigated in 3.0 wt% NaCl solutions. For this purpose, scanning Kelvin probe (SKP), open-circuit potential (Eocp), polarization curves, and cyclic voltammetry techniques were used. The influence of electro-synthesis method and parameters were analyzed. It was found that the deviation in the Volta potentials is correlated to the interfacial interaction between the PPy/Ni bilayer coating and substrate. Considering both experimental methods to obtain PPy/Ni coatings, a more effective protection against corrosion can be formed when potentiodynamic (cyclic voltammetry) and potentiostatic techniques are combined.Peer Reviewe

Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes

Many genomic alterations associated with human diseases localize in noncoding regulatory elements located far from the promoters they regulate, making it challenging to link noncoding mutations or risk-associated variants with target genes. The range of action of a given set of enhancers is thought to be defined by insulator elements bound by the 11 zinc-finger nuclear factor CCCTC-binding protein (CTCF). Here we analyzed the genomic distribution of CTCF in various human, mouse and chicken cell types, demonstrating the existence of evolutionarily conserved CTCF-bound sites beyond mammals. These sites preferentially flank transcription factor–encoding genes, often associated with human diseases, and function as enhancer blockers in vivo, suggesting that they act as evolutionarily invariant gene boundaries. We then applied this concept to predict and functionally demonstrate that the polymorphic variants associated with multiple sclerosis located within the EVI5 gene impinge on the adjacent gene GFI1.This research was supported by the following grants: BFU2007-60042/BMC, BFU2010-14839, Petri PET2007_0158, CONSOLIDER CSD2007-00008 (Spanish Ministerio de Ciencia e Innovación (MICINN)) and Proyecto de Excelencia CVI-3488 (Junta de Andalucía) to J.L.G.-S.; BFU2009-07044 (MICINN) and Proyecto de Excelencia CVI 2658 (Junta de Andalucía) to F.C.; FIS PI081636 (ISCIII) to F.M.; PN-SAF2009-11491 (MICINN) and Proyecto de Excelencia P07-CVI-02551 (Junta de Andalucía) to A.A.; BFU2008-00838, CONSOLIDER CSD2007-00008 (MICINN), Regional Government of Madrid (CAM S-SAL-0190-2006) and the Pro-CNIC Foundation to M.M.; BFU2006-12185 and BIO2009-12697 (MICINN) to L.M.; Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (IN209403, IN214407 and IN203811) and Consejo Nacional de Ciencia y Tecnología, México (CONACyT: 42653-Q, 58767 and 128464) to F.R.-T.; Intramural Research Program of the US NCBI (NIH) to I.O. and BIO2006-03380, CONSOLIDER CSD2007-00050 (MICINN) and RETICS RD07/0067/0012 (Spanish MICINN) to R.G. L.M. thanks A. Fernández for technical assistance and L. Barrios for statistical analysis. F.R.-T. thanks G.G. Avendaño for technical assistance