Optimización del tratamiento anticipado de la infección por citomegalovirus en el receptor de transplante de órgano sólido.

El objetivo principal de la presente tesis doctoral es definir acciones que nos permitan optimizar el tratamiento anticipado como estrategia preventiva de la infección por citomegalovirus utilizando los nuevos avances tecnológicos y del conocimiento, de los que ahora disponemos, que facilitan y mejoran el diagnóstico y la monitorización virológica e inmunológica de la infección. Para ello en primer lugar, se plantea como objetivo determinar un umbral estándar de replicación para el inicio del tratamiento anticipado según el riesgo del paciente de desarrollar infección por citomegalovirus. En segundo lugar, determinar las diferencias entre infección primaria y recurrente y, analizar el impacto de la adquisición de la respuesta inmune específica de células T frente a CMV y el uso de la profilaxis secundaria en la ocurrencia de infección recurrente en el paciente con serología negativa para litomegalovirus previa al trasplante. En tercer lugar, analizar el impacto clínico de la neutropenia relacionada con el tratamiento anticipado con valganciclovir, determinando los factores de riesgo que la producen y aquellos que pueden minimizarla. Apoyándonos sobre estos tres pilares, podremos individualizar el tratamiento anticipado, mejorar su manejo y su aplicabilidad clínica en el receptor de trasplante de órgano sólido infectado por citomegalovirus.Premio Extraordinario de Doctorado U

An N-annulated, rylene-based twistacene as scaffold for long supramolecular polymers

The multistep synthesis of the N-annulated rylenecarbodiimide 1 is reported. The large p-surface and the operation of a fourfold array of H-bonding interactions between the trialkoxybenzamide units yield highly stable supramolecular polymers, the stability of which has been quantified by applying the denaturation model. The operation of these non-covalent interactions affords long 1D-supramolecular polymers that have been visualized by atomic force microscopy (AFM)

Prevalence and Risk Factors for Multidrug-Resistant Organisms Colonization in Long-Term Care Facilities Around the World: A Review

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.The study was funded by the Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness (grant number: PI17-02195) and was partially funded by the European Development Regional Fund “A way to achieve Europe”. A.R.V. and A.B.G.G. are supported by the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain. A.R.V. grant number: CM18/00122. A.B.G.G. grant number: CM19/00029. C.M.G. and J.C.C.R. are supported by the Instituto de Salud Carlos III (grant number: PI17-02195) and co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0009).G.P. is supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001)- co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020. M.E.P.I. is a postdoctoral researcher belonging to the program “Nicolás Monardes” (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. J.M.C. received funding for research from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0009), co-financed by the European Development Regional Fund “A way to achieve Europe”.Ye

Redox-Active Hybrid Polyoxometalate-Stabilised Gold Nanoparticles

We report the design and preparation of multifunc-tional hybrid nanomaterials through the stabilization of goldnanoparticles with thiol-functionalised hybrid organic–inor-ganic polyoxometalates (POMs). The covalent attachment ofthe hybrid POM forms new nanocomposites that are stable attemperatures and pH values which destroy analogous electro-statically functionalised nanocomposites. Photoelectrochemi-cal analysis revealed the unique photochemical and redoxproperties of these systems.Leverhulme Trust del Reino Unido-RPG-2016-442Engineering and Physical Sciences Research Council del Reino Unido (EPSRC)-EP/ P002382/1Centre of Advanced Materials for Integrated Energy Systems del Reino Unido-CAM-IESGeneralitat Valenciana-CIDEGENT/2018/03

Chlorophyll catabolism in olive fruits (var. Arbequina and Hojiblanca) during maturation

3 Tablas.-- 3 FigurasThe central reaction of chlorophyll (chl) breakdown pathway occurring during olive fruits maturation is the cleavage of the macrocycle pheophorbide a to a primary fluorescent chl catabolite (pFCC) and it is catalyzed by two enzymes: pheophorbide a oxygenase (PaO) and red chl catabolite reductase (RCCR). In subsequent steps, pFCC is converted to different fluorescent chlorophyll catabolites (FCCs) and nonfluorescent chlorophyll catabolites (NCCs). This work demonstrated that RCCR activity of olive fruits is type II. During the study of evolution of PaO and RCCR activities through the olive fruits maturation in two varieties: Hojiblanca and Arbequina, a significant increase in PaO and RCCR activity was found in ripening stage. In addition, the profile and structure of NCCs present in epicarp of this fruit was studied using HPLC/ESI-TOF-MS. Five different NCCs were defined and for the first time the enzymatic reactions implied in chlorophyll degradations in olive fruits elucidated.This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT-EU, Spanish and European Government, AGL 2015-63890-R) and by Junta de Andalucía (AGR 6271-2011)

More about the safety of tigecycline for the treatment of infectious diseases: The role of superinfection rates

We have read with great interest papers published concerning the efficacy and safety of tigecycline and the ensuing correspondence. Mortality has been reported in most of the publications to be higher with tigecycline in comparison with other antimicrobial agents. However, we would like to make some remarks on the role of superinfection rates during treatment with tigecycline, and the impact on safety. Tigecycline was approved by the US FDA for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections (2005), and for community-acquired pneumonia (2009). Due to the high rates of multidrug-resistant (MDR) pathogens and the scarcity of new antibacterial agents, the use of tigecycline was extended to the treatment of colistin-resistant Acinetobacter baumannii infections, and as an alternative for patients allergic to β-lactam antimicrobial agents, by the Commission of Infections and Antimicrobial Policy in our hospital.The Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD06/0008) supported this work.Peer Reviewe

Comparison of two quantitative real-time CMV-PCR tests calibrated against the 1st WHO international standard for viral load monitoring of renal transplant patients

Cytomegalovirus (CMV) replication in organ transplant recipients is commonly diagnosed by quantitative PCR methods. However, there has been a poor inter-laboratory correlation of viral load values due to the lack of an international reference standard. In a recent study, the COBAS(R) AmpliPrep/COBAS(R) TaqMan(R) (CAP/CTM) CMV test calibrated to the 1st WHO CMV standard, showed good reproducibility in CMV load values across multiple laboratories. Fifty-seven follow-up plasma specimens from 10 kidney transplant recipients with CMV replication were examined using the new quantitative CAP/CTM CMV test and the "in-house" quantitative CMV real-time PCR method, also calibrated against the 1st WHO CMV standard for their clinical applicability for monitoring CMV load in renal transplant patients. By CAP/CTM CMV test 49/57 specimens were CMV-DNA positive compared to 44/57 by the "in-house" PCR test. The "in-house" PCR and CAP/CTM CMV test correlated well in monitoring individual kidney transplant patients. Conversion of the CMV-DNA copies to IUs made the results of the "in-house" PCR and CAP/CTM CMV test less uniform in analysis of the patient samples. In specimens of one patient, significant underquantification of CMV load with "in-house" PCR emerged during follow-up due to a point mutation in the "in-house" PCR primer sequence. The CAP/CTM CMV test was found suitable for diagnosing and monitoring CMV replication in renal transplant patients. Multicenter studies are needed to provide more information of the commutability of the 1st WHO CMV standard and to define the clinical thresholds. J. Med. Virol. (c) 2013 Wiley Periodicals, Inc