Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients

Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.This study was funded by the Consejería de Salud (Grant Number: PI-0119-2012), Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (Grant Numbers: GR09/0041, PI14-00165, and MPY110/18) and co-financed by European Development Regional Fund “A way to achieve Europe” ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015/0001)

Efficacy and safety of a booster dose of influenza vaccination in solid organ transplant recipients, TRANSGRIPE 1-2: study protocol for a multicenter, randomized, controlled clinical trial

BACKGROUND: Despite administration of annual influenza vaccination, influenza-associated complications in transplant recipients continue to be an important cause of hospitalization and death. Although influenza vaccination has been proven to be the most effective measure to reduce influenza infection after transplantation, transplant recipients are still vulnerable to influenza infections, with lower serological responses to vaccination compared to the general population. In order to assess the efficacy and safety of an alternative immunization scheme for solid organ transplant recipients, the TRANSGRIPE1-2 Study Group aimed to test a booster dose administration 5 weeks after the standard vaccination. The primary objective of this trial was to compare short-term and long-term neutralizing antibody immunogenicity of a booster dose of influenza vaccination to the standard single-dose immunization scheme. Secondary objectives included the evaluation of the efficacy and/or safety, cellular immune response, incidence of influenza infection, graft rejection, retransplant and mortality rates. METHODS/DESIGN: This phase III, randomized, controlled, open-label clinical trial was conducted between October 2012 and December 2013 in 12 Spanish public referral hospitals. Solid organ transplant recipients (liver, kidney, heart or lung), older than 16 years of age more than 30 days after transplantation were eligible to participate. Patients (N = 514) were stratified 1:1 by center, type of organ and time after transplantation and who either received the standard single dose (n = 257) or were treated according to a novel influenza vaccination schedule comprising the administration of a booster dose 5 weeks after standard vaccination (n = 254). Seroconversion rates were measured as a determinant of protection against influenza (main outcome). Efficacy and safety outcomes were followed until 1 year after influenza vaccination with assessment of short-term (0, 5, 10 and 15 weeks) and long-term (12 months) results. Intention-to-treat, per-protocol and safety analyses will be performed. DISCUSSION: This trial will increase knowledge about the safety and efficacy of a booster dose of influenza vaccine in solid organ transplant recipients. At the time the manuscript was submitted for publication, trial recruitment was closed with a total of 499 participants included during a 2-month period (within the seasonal influenza vaccination campaign). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01761435 (registered 13 December 2012). EudraCT Identifier: 2011-003243-21 (registered 4 July 2011)

Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC90 increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC90 decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.This study has been funded by Instituto de Salud Carlos III, through the projects PI17/01405 and PI20/01255, by the Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía, Industria y Competitividad, US-1381501 US/JUNTA/FEDER, UE, by the Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, and the Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0009) and co-funded by the European Union.Peer reviewe

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 10

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 10, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

COMPORTAMIENTO ESTRUCTURAL DE PUENTES EXTRADOSADOS DURANTE CONSTRUCCIÓN POR VOLADIZOS SUCESIVOS (STRUCTURAL BEHAVIOR OF EXTRADOSED BRIDGES DURING CANTILEVER CONSTRUCTION)

Este artículo presenta el estudio del comportamiento durante construcción por voladizos sucesivos de un puente extradosado en concreto de tres luces (60+100+60 m), modelado numéricamente mediante elementos finitos en el software SAP2000. La fluencia y contracción del concreto, al igual que los efectos P-delta, se incluyeron en el modelamiento. El estudio se concentró en el comportamiento del tablero, los cables y los pilares, durante construcción y desde el momento del cierre hasta cincuenta años después, tiempo en el cual han ocurrido los efectos diferidos. Los resultados encontrados permiten vislumbrar la importancia de la consideración de estos efectos en el análisis por etapas del puente. Por ejemplo, en el tablero ocurren variaciones considerables en fuerzas internas y desplazamientos en el tiempo, y en los cables tiene lugar una pérdida de tensión máxima del 10 % con respecto a la tensión al final de construcción. En los pilares, los efectos diferidos en el tiempo causan desplazamientos horizontales de magnitud considerable en la corona, generando momentos flectores excesivos en la base. Lo anterior obliga a introducir una fuerza durante la construcción de la dovela de cierre para corregir dicho fenómeno.Abstract: This paper presents the results of the study of the structural behavior during cantilever construction of a concrete,three-span (60+100+60 m) extradosed bridge, numerically modeled using a finite element model developed in the software SAP2000. Creep and shrinkage of concrete, as P-delta effects were taken into account. The study focuses on deck, extradosed cables and piers behavior, during construction, and from the time when the bridge is closed until fifty years, at which time all differed effects have taken place. It was possible to glimpse the importance of considering thediffered effects over time in the staged-construction analysis of the bridge. For example, considerable variations in forces and displacements were found in the deck, while a 10% tension loss in extradosed cables occurs. In the piers, differed effects introduce large horizontal displacements at the top which generate excessive bending moments at the bottom. This fact makes it necessary to apply a force during the construction of the closing segment to correct such phenomenon.Sumário: Este artigo apresenta o estudo do comportamento durante construção por ressaltados sucessivos dum ponte extradorso em concreto de três luzes (60+100+60 m), modelado numéricamente mediante elementos finitos no software SAP2000. A fluência e contração do concreto, da mesma forma que os efeitos P-delta, incluíram-se no modelamento. Este estudo concentrou-se no comportamento do tabuleiro, os cabos e os pilares, durante construção e desde o momento do fecho até cinqüenta anos depois, tempo no qual aconteceram os efeitos diferidos. Os resultados encontrados permiten vislumbrar a importância da consideração destos efeitos na análise por etapas do ponte. Por exemplo, no tabuleiro acontecem variações consideráveis em forças internas e deslocamentos no tempo, e nos cabos tem lugar uma perda de tensão máxima do 10% com respeito à tensão ao final de construção. Nos pilares, os efeitos diferidos no tempo causam deslocamentos horizontais de magnitude considerável na coroa, gerando momentos flectores excessivos na base. O anterior obriga a introduzir uma força durante a construção da aduela de fecho para corrigir este fenômeno.Este artículo presenta el estudio del comportamiento durante construcción por voladizos sucesivos de un puente extradosado en concreto de tres luces (60+100+60 m), modelado numéricamente mediante elementos finitos en el software SAP2000. La fluencia y contracción del concreto, al igual que los efectos P-delta, se incluyeron en el modelamiento. El estudio se concentró en el comportamiento del tablero, los cables y los pilares, durante construcción y desde el momento del cierre hasta cincuenta años después, tiempo en el cual han ocurrido los efectos diferidos. Los resultados encontrados permiten vislumbrar la importancia de la consideración de estos efectos en el análisis por etapas del puente. Por ejemplo, en el tablero ocurren variaciones considerables en fuerzas internas y desplazamientos en el tiempo, y en los cables tiene lugar una pérdida de tensión máxima del 10 % con respecto a la tensión al final de construcción. En los pilares, los efectos diferidos en el tiempo causan desplazamientos horizontales de magnitud considerable en la corona, generando momentos flectores excesivos en la base. Lo anterior obliga a introducir una fuerza durante la construcción de la dovela de cierre para corregir dicho fenómeno.Abstract: This paper presents the results of the study of the structural behavior during cantilever construction of a concrete,three-span (60+100+60 m) extradosed bridge, numerically modeled using a finite element model developed in the software SAP2000. Creep and shrinkage of concrete, as P-delta effects were taken into account. The study focuses on deck, extradosed cables and piers behavior, during construction, and from the time when the bridge is closed until fifty years, at which time all differed effects have taken place. It was possible to glimpse the importance of considering thediffered effects over time in the staged-construction analysis of the bridge. For example, considerable variations in forces and displacements were found in the deck, while a 10% tension loss in extradosed cables occurs. In the piers, differed effects introduce large horizontal displacements at the top which generate excessive bending moments at the bottom. This fact makes it necessary to apply a force during the construction of the closing segment to correct such phenomenon.Sumário: Este artigo apresenta o estudo do comportamento durante construção por ressaltados sucessivos dum ponte extradorso em concreto de três luzes (60+100+60 m), modelado numéricamente mediante elementos finitos no software SAP2000. A fluência e contração do concreto, da mesma forma que os efeitos P-delta, incluíram-se no modelamento. Este estudo concentrou-se no comportamento do tabuleiro, os cabos e os pilares, durante construção e desde o momento do fecho até cinqüenta anos depois, tempo no qual aconteceram os efeitos diferidos. Os resultados encontrados permiten vislumbrar a importância da consideração destos efeitos na análise por etapas do ponte. Por exemplo, no tabuleiro acontecem variações consideráveis em forças internas e deslocamentos no tempo, e nos cabos tem lugar uma perda de tensão máxima do 10% com respeito à tensão ao final de construção. Nos pilares, os efeitos diferidos no tempo causam deslocamentos horizontais de magnitude considerável na coroa, gerando momentos flectores excessivos na base. O anterior obriga a introduzir uma força durante a construção da aduela de fecho para corrigir este fenômeno

Modulating fatty acid epoxidation vs. hydroxylation in a fungal peroxygenase

1 p.-3 fig.Unspecific peroxygenases (UPOs) are fungal secreted counterparts of the cytochrome P450 monooxygenases present in most living cells. Both enzyme types share the ability to perform selective oxygenation reactions. Moreover, the Marasmius rotula UPO (MroUPO) catalyzes reactions of interest compared with the previously described UPOs, including formation of reactive epoxy fatty acids. To investigate substrate epoxidation, the most frequent positions of oleic acid at the MroUPO heme channel were predicted using binding and molecular dynamics simulations. Then, mutations in neighbor residues were designed aiming at modulating the enzyme epoxidation vs hydroxylation ratio. Both the native (wild-type recombinant) MroUPO and the mutated variants were expressed in Escherichia coli as active enzymes, and their action on oleic and other fatty acids was investigated by gas chromatography−mass spectrometry in combination with kinetic analyses. Interestingly, a small modification of the cannel shape in the I153T variant increased the ratio between epoxidized oleic acid and its additionally hydroxylated derivatives. A fully opposite effect was attained with the double I153F/S156F variant that completely abolished the ability of the MroUPO to epoxidize oleic acid (while no activity was detected for the I153V variant). The rationale for these results was revealed by the substrate positioning in the above computational simulations, which predict a shorter distance between the oleic acid double bond and the oxygen atom of the peroxide-activated heme (compound I) in the I153T variant than in the native enzyme, promoting epoxidation. In contrast, the I153F/S156F double mutation fully prevents the approach of oleic acid in the bent conformation required for double-bond epoxidation, although its (sub)terminal hydroxylation was predicted and experimentally confirmed. The I153T mutation also increased the UPO selectivity on polyunsaturated fatty acid epoxidation, strongly reducing the ratio between simple epoxides and their hydroxylated derivatives, with respect to the native UPO.Peer reviewe

Unspecific peroxygenase enzyme variants for selective fatty acid epoxidation or hydroxylation

The invention relates to a recombinant Marasmius rotula unspecific peroxygenase (rMroURO) and two mutants thereof, wherein said mutants show enhanced selectivity towards either the epoxidation or the (sub)terminal ω/(ω- 1)-hydroxylation of unsaturated fatty acids. The invention also refers to the use of these enzyme variants for the specific epoxidation or hydroxylation of fatty acids such as oleic acid, linoleic acid and/or alpha-linolenic acid.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

A first step towards the development of a sustainable top-of-rail friction modifier based on avocado oil

Comunicación congreso presentado en el 9th International Tribology Conference, (ITC Fukuoka 2023 ) 25-30 sept. Fukuoka (Japan) (2023)A new approach for developing a top-of-rail friction modifier based on avocado oil has been explored. Our goal was to employ, when possible, only environmentally friendly and sustainable components and additives: residuals of avocado oil production, natural antioxidants, natural thickeners, and the additives to control friction and wear, since top-of-rail friction modifier ends up in the environment. There is special concern about the environmental safety of urban passenger railway transport. At the first stage of the study, the chemical, physical, rheological, and tribological properties of natural avocado oil were extensively explored. This is the first time that avocado oil has been studied for lubrication purposes for applications different from food, cosmetics, or pharmaceutics. It was found that avocado oil has the good lubricating capability and a viscosity index of 200 according to ASTM D2270-10(2016), as well as a complex non-linear rheological behaviour under low shear rates. The fatty acid profile was measured using reverse-phase liquid chromatography equipped with a Diode Array detector and coupled to QTOF Mass Spectrometer. The main components were the following: C18:1 oleic acid - 66.4%, C16:1 palmitic acid - 16.9%, C18:2 linoleic acid - 7.79%, and other acids in small quantities. The tribological properties of the natural oil (triglycerides) were compared with the isolated fatty acids and their methyl esters. In the "four balls" test under the ASTM D2783 standard. The natural oil showed better protection under extreme pressure conditions than the isolated fatty acids or methyl transesterified oil. No chemical changes in the oil were found after the tribological tests using FTIR and NMR spectroscopy. Natural avocado oil was less corrosive than the benchmark trimethylolpropane oleate according to the copper strip corrosion test (ASTM D 130-18)

Exploration of alternative base stock vegetable oils for the development of a sustainable top-of-rail friction modifier

Avocado oil or coffee oil obtained from residues can be a good alternative for the base stock of sustainable lubricants. In this work we explore avocado oil as a prospective base stock for a top-of-rail friction modifier. Our goal was to employ, when possible, only environmentally friendly and sustainable components and additives: residuals of avocado oil production, natural antioxidants, natural thickeners, and the additives to control friction and wear, since top-of-rail friction modier ends up in the environment. There is special concern about the environmental safety of urban passenger railway transport. Furthermore, the revalorization of agricultural residues can help the local society to increase income and reduce the pressure on the ecosystems. At the rst stage of the study, the chemical, physical, rheological, and tribological properties of natural avocado oil were extensively explored. This is the first time that avocado oil has been studied for lubrication purposes for applications different from food, cosmetics, or pharmaceutics. It was found that avocado oil has good lu- bricating capability and a viscosity index of 200 according to ASTM D2270-10(2016), as well as a complex non-linear rheological behaviour under low shear rates. The fatty acid prole was measured using reverse-phase liquid chromatography equipped with a Diode Array detector and coupled to QTOF Mass Spectrometer. The main components were the following: C18:1 oleic acid -66.4%, C16:1 palmitic acid -16.9%, C18:2 linoleic acid -7.79%, and other acids in small quantities. The tribological properties of the natural oil (triglycerides) were compared with the isolated fatty acids and their methyl esters. In the "four balls¿ test under the ASTM D2783 standard. The natural oil showed better protection under extreme pressure conditions than the isolated fatty acids or methyl transesterified oil. No chemical changes in the oil were found after the tribological tests using FTIR and NMR spectroscopy. Natural avocado oil was less corrosive than the benchmark trimethylolpropane oleate according to the copper strip corrosion test (ASTM D 130-18)

Engineering Collariella virescens Peroxygenase for Epoxides Production from Vegetable Oil

17 páginas.- 4 figuras.- 4 tablas.- 46 referencias.- Supplementary Materials: The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/antiox11050915/s1Vegetable oils are valuable renewable resources for the production of bio-based chemicals and intermediates, including reactive epoxides of industrial interest. Enzymes are an environmentally friendly alternative to chemical catalysis in oxygenation reactions, epoxidation included, with the added advantage of their potential selectivity. The unspecific peroxygenase of Collariella virescens is only available as a recombinant enzyme (rCviUPO), which is produced in Escherichia coli for protein engineering and analytical-scale optimization of plant lipid oxygenation. Engineering the active site of rCviUPO (by substituting one, two, or up to six residues of its access channel by alanines) improved the epoxidation of individual 18-C unsaturated fatty acids and hydrolyzed sunflower oil. The double mutation at the heme channel (F88A/T158A) enhanced epoxidation of polyunsaturated linoleic and α–linolenic acids, with the desired diepoxides representing > 80% of the products (after 99% substrate conversion). More interestingly, process optimization increased (by 100-fold) the hydrolyzate concentration, with up to 85% epoxidation yield, after 1 h of reaction time with the above double variant. Under these conditions, oleic acid monoepoxide and linoleic acid diepoxide are the main products from the sunflower oil hydrolyzate. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This research was funded by BioBased Industries Joint Undertaking under the European Unions Horizon 2020 Research and Innovation Programme, grant number 792063 (SusBind project; https://susbind.eu; to A.G and A.T.M.); the BIO2017-86559-R project of the Spanish Ministry of Science and Innovation (co-financed by FEDER funds; to A.T.M.); the PID2020-118968RB-I00 project by the Spanish MCIN/AEI/10.13039/501100011033 (to A.G.); the CSIC projects PIE-202040E185 (to A.G.) and PIE-202120E019 (to A.T.M.); the CSIC SusPlast platform (to A.T.M.); and the CSIC program for the Spanish Recovery, Transformation, and Resilience Plan funded by the Recovery and Resilience Facility of the European Union, established by the Regulation (EU) 2020/2094.Peer reviewe