Uso de antivirales de acción directa en población coinfectada VIH/VHC

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 24-10-201

NaCl-induced physiological and biochemical adaptative mechanisms in the ornamental Myrtus communis L. plants

Physiological and biochemical changes in Myrtus communis L. plants after being subjected to different solutions of NaCl (44, and 88mM) for up to 30 days (Phase I) and after recovery from the salinity period (Phase II) were studied. Myrtle plants showed salinity tolerance by displaying a series of adaptative mechanisms to cope with salt-stress, including controlled ion homeostasis, the increase in root/shoot ratio, the reduction of water potentials and stomatal conductance to limit water loss. In addition, they displayed different strategies to protect the photosynthetic machinery, including limiting toxic ion accumulation in leaves, increase in chlorophyll content, and changes in chlorophyll fluorescence parameters, leaf anatomy and increases in catalase activity. Anatomical modifications in leaves, including a decrease in spongy parenchyma and increased intercellular spaces, allow CO2 diffusion in a situation of reduced stomatal aperture. In spite of all these changes, salinity produced oxidative stress in myrtle plants as monitored by increases in oxidative stress parameter values. The post-recovery period is perceived as a new stress situation, as observed through effects on plant growth and alterations in non-photochemical quenching parameters and lipid peroxidation values. © 2015 Elsevier GmbH.This work was supported by the Spanish Ministry of Economy and Competitiveness co-financed by FEDER funds (Project CICYT AGL 2011-30022-C02-01-02) and by The Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia (11883/PI/09 and 15356/PI/10). PDV acknowledges the CSIC and the Spanish Ministry of Economy and Competitiveness for his ‘Ramon y Cajal’ research contract, co-financed by FEDER funds.Peer Reviewe

Physiological and biochemical mechanisms of the ornamental Eugenia myrtifolia L. plants for coping with NaCl stress and recovery

Main Conclusion: We studied the response ofEugenia myrtifoliaL. plants, an ornamental shrub native to tropical and subtropical areas, to salt stress in order to facilitate the use of these plants in Mediterranean areas for landscaping.E. myrtifoliaplants implement a series of adaptations to acclimate to salinity, including morphological, physiological and biochemical changes. Furthermore, the post-recovery period seems to be detected by Eugenia plants as a new stress situation. Different physiological and biochemical changes in Eugenia myrtifolia L. plants after being subjected to NaCl stress for up to 30 days (Phase I) and after recovery from salinity (Phase II) were studied. Eugenia plants proved to be tolerant to NaCl concentrations between 44 and 88 mM, displaying a series of adaptative mechanisms to cope with salt-stress, including the accumulation of toxic ions in roots. Plants increased their root/shoot ratio and decreased their leaf area, leaf water potential and stomatal conductance in order to limit water loss. In addition, they displayed different strategies to protect the photosynthetic machinery, including the limited accumulation of toxic ions in leaves, increase in chlorophyll content, changes in chlorophyll fluorescence parameters, leaf anatomy and antioxidant defence mechanisms. Anatomical modifications in leaves, including an increase in palisade parenchyma and intercellular spaces and decrease in spongy parenchyma, served to facilitate CO2 diffusion in a situation of reduced stomatal aperture. Salinity produced oxidative stress in Eugenia plants as evidenced by oxidative stress parameters values and a reduction in APX and ASC levels. Nevertheless, SOD and GSH contents increased. The post-recovery period is detected as a new stress situation, as observed through effects on plant growth and alterations in chlorophyll fluorescence and oxidative stress parameters. © 2015, Springer-Verlag Berlin Heidelberg.This work was supported by the Spanish Ministry of Economy and Competitiveness co-financed by FEDER funds (Project CICYT AGL 2011-30022-C02-01-02) and by The Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia (11883/PI/09 and 15356/PI/10). Authors thank Mrs Ansley Evans for correction of the English.Peer Reviewe

Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPARγ and 5-LO-dependent pathways.

PPARγ-achieved neuroprotection in experimental stroke has been explained by the inhibition of inflammatory genes, an action in which 5-LO, Alox5, is involved. In addition, PPARγ is known to promote the expression of CD36, a scavenger receptor that binds lipoproteins and mediates bacterial recognition and also phagocytosis. As phagocytic clearance of neutrophils is a requisite for resolution of the inflammatory response, PPARγ-induced CD36 expression might help to limit inflammatory tissue injury in stroke, an effect in which 5-LO might also be involved. Homogenates, sections, and cellular suspensions were prepared from brains of WT and Alox5(-/-) mice exposed to distal pMCAO. BMMs were obtained from Lys-M Cre(+) PPARγ(f/f) and Lys-M Cre(-) PPARγ(f/f) mice. Stereological counting of double-immunofluorescence-labeled brain sections and FACS analysis of cell suspensions was performed. In vivo and in vitro phagocytosis of neutrophils by microglia/macrophages was analyzed. PPARγ activation with RSG induced CD36 expression in resident microglia. This process was mediated by the 5-LO gene, which is induced in neurons by PPARγ activation and at least by one of its products--LXA4--which induced CD36 independently of PPARγ. Moreover, CD36 expression helped resolution of inflammation through phagocytosis, concomitantly to neuroprotection. Based on these findings, in addition to a direct modulation by PPARγ, we propose in brain a paracrine model by which products generated by neuronal 5-LO, such as LXA4, increase the microglial expression of CD36 and promote tissue repair in pathologies with an inflammatory component, such as stroke.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness CSD2010-00045 (to M.A.M.) SAF2009-08145 and SAF2012-33216 (to M.A.M.), SAF2011-23354 (toI.L.), SAF2009-07466 and SAF2012-31483 (to M.R.), from Fondo Europeo de Desarrollo Regional (FEDER) “Instituto de Salud Carlos III” RETICS RD12/0014/0003 (to I.L. and from the local govern-ment of Madrid S2010/BMD-2336 (to M.A.M.) and S2010/BMD-2349 (to I.L.). I.B. and M.I.C. are fellows of the Spanish Ministry ofEconomy and Competitiveness. The authors thank Tamara Atanesand Roberto Cañadas for their technical assistance.S

Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients

We assessed the effect of co-infection by hepatitis C virus (HCV) on immunological and virological response at 48 weeks from initiation of antiretroviral therapy (ART).We included patients from the Cohort of Spanish HIV Research Network (CoRIS) starting ART between January 2004 and November 2014, had at least 1 CD4 T-cell count and viral load measurements both in the previous 6 months and at 48 (±12) weeks from ART initiation, and HCV serology before ART initiation. We used linear regression for mean differences in CD4 T-cell count increase from ART initiation and logistic regression to estimate odds ratios for virological response.Of 12,239 patients by November 30, 2015, 5070 met inclusion criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co-infected patients were more likely to have acquired HIV through injecting drugs use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational level, and having started ART with lower CD4 counts and acquired immunodeficiency syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/μL in HIV-monoinfected and 161.9 cell/μL in HIV/HCV-coinfected patients. The percentages of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in mono and coinfected patients, respectively. Multivariable analyses showed that at 48 weeks, coinfected patients increased 44.5 (95% confidence interval [CI]: 24.8-64.3) cells/μL less than monoinfected and had lower probability of virological response (odds ratio: 0.62; 95% CI: 0.44-0.88).HIV/HCV-coinfected patients have lower immunological and virological responses at 48 weeks from ART initiation than monoinfected patients.This work has been supported by the Spanish Medical Fund Research (PI12/02134) and Spanish Research Network of Excellence on HIV (RD12/0017/0018, RD16CIII/0002/0006) and Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP).S

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naive patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) & GE;200 copies/mL at 24 weeks or as a single determination of VL & GE;1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naive patients with CD4+ nadir <100 cells/& mu;L were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available

HIV and HCV screening by non-infectious diseases physicians: can we improve testing and hidden infection rates?

BackgroundMissed opportunities for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) testing remain high. We aimed to ascertain the knowledge of screening guidelines and attitudes of non-infectious disease (ID) hospital physicians and assess the impact of a 1-h session on screening rates and diagnoses.MethodsThis interventional study consisted of a 1-h training session on HIV and HCV epidemiology and testing guidelines for non-ID physicians. Pre-and post-session questionnaires compared the knowledge of the guidelines and attitudes toward screening before and after the session. Rates of screening and diagnoses were compared in three 6 months periods: before, immediately after, and 24 months ±4 after the session.ResultsA total of 345 physicians from 31 departments participated in these sessions. Before the session, 19.9% (28% medical, 8% surgical) and 17.9% (30% medical, 2.7% surgical) were aware of HIV and HCV testing guidelines, respectively. The willingness to routinely test increased from 5.6 to 22%, whereas not ordering tests decreased from 34.1 to 2.4%. HIV screening rates significantly increased by 20% after the session (7.7 vs. 9.3 tests per 103 patients; p &lt; 0.001), and the effect persisted until the long-term period. The HIV diagnosis rate increased globally (3.6 vs. 5.2 HIV diagnoses per 105 patients; p = 0.157), mainly because of medical services (4.7 vs. 7.7 per 105 patients; p = 0.082). The HCV screening rate increased significantly immediately and in the long term only in medical services (15.7 and 13.6%, respectively). The new active HCV infection rates increased immediately and declined steeply thereafter.ConclusionA short session for non-ID physicians can improve HIV/HCV screening, increase diagnosis, and contribute to disease elimination

Metodología sistemática de análisis de patologías en morteros

En la actualidad, existe una clara necesidad de implantar metodologías que contribuyan a facilitar la comunicación entre los profesionales de diferentes campos del conocimiento implicados en el ámbito de las patologías en construcción, para disminuir la subjetividad inherente a cada profesional a la hora de tomar decisiones con respecto a la aplicación de técnicas analíticas que permitan identificar el problema que se ha producido. Con este trabajo se busca aprovechar las sinergias existentes entre los agentes implicados en el proceso constructivo con conocimientos transversales en el campo del análisis, conservación, reparación y restauración en su caso, cuya finalidad sería la de obtener mayor número de datos de entrada y, por tanto, enriquecer los contenidos y las conclusiones previas a la fase de intervención propiamente dicha, desarrollando una metodología para la selección de técnicas analíticas y/o ensayos aplicables a una patología en cada caso concreto. El presente trabajo de investigación, el cual se encuentra en fase inicial, tiene como objetivo final desarrollar una propuesta metodológica que sirva de guía a los profesionales implicados en el proceso constructivo, a la hora de seleccionar las técnicas de análisis y/o ensayos más adecuados de análisis para el estudio de las distintas patologías que pudieran aparecer en los diferentes tipos de morteros y para cada caso concreto. La investigación se inicia llevando a cabo una recopilación de todas las patologías posibles, ya sean comunes o de escasa incidencia, en todo tipo de morteros y aplicaciones constructivas. Esto se hará en base al análisis bibliográfico, consultas a laboratorios especializados y a datos estadísticos, así como a diversos grupos de investigación especializados en la materia. Una vez estudiadas y clasificadas todas las patologías en función de la tipología de mortero y su función constructiva, se establecerán para cada una de ellas las técnicas posibles de análisis que permitan establecer la causa u origen más probable de la lesión en cuestión. El paso final será desarrollar una propuesta metodológica que será validada mediante la aplicación del método Delphi de manera que permita establecer el grado de idoneidad de las diferentes técnicas de análisis para cada patología, pudiendo seleccionar las más apropiada en función de su adecuación al problema y a la casuística que lo acompaña. Este método de pronóstico consiste en una consulta a un grupo de expertos en forma individual por medio de la interacción sucesiva de un cuestionario apoyado por los resultados promedio de la ronda anterior con el fin de generar convergencia de opiniones de manera que se comprobaría, verificando o modificando la hipótesis planteada en la metodología propuesta

Multidomain Healthy-Age Programme. Recomendations for Healthy Ageing: On Behalf of the Healthy-Age Network

La Red de investigación en Envejecimiento Activo, Ejercicio y Salud: HEALTHY-AGE (referencias: 06/ UPR/19 y 08/UPR/20) está respaldada por subvención del Consejo Superior de Deportes (CSD) del Ministerio de Cultura y Deporte del gobierno de España –convocatoria de 2019 y 2020 de Redes de Ciencias del Deporte–. Los autores declaran no poseer conflictos de interés.El envejecimiento es un proceso natural asociado a un declive que repercute en un mayor riesgo de padecer discapacidad física y cognitiva, y/o afección emocional y social. En consecuencia, diversos estudios muestran los múltiples beneficios de los programas de entrenamiento multicomponente. Además, las directrices actuales amplían este enfoque hacia los programas multidominio. Por ello, el objetivo de este trabajo es presentar el programa de intervención multidominio Healthy-Age que sigue las recomendaciones de las principales instituciones y literatura científica e incluye los principales dominios (físico, social, cognitivo y motivacional) en las personas mayores. Su finalidad es la de prevenir, mantener o mejorar la salud integral (física, psíquica, emocional y social) y educarles para un envejecimiento saludable. Además de incluir unas recomendaciones generales de actividad física, se muestran recomendaciones para el entrenamiento de la resistencia aeróbica, el equilibrio, la coordinación, la fuerza y resistencia muscular, la flexibilidad y el entrenamiento cognitivo; y se presentan dos modalidades; un plan de 5 días supervisado y un plan de 3 días supervisado más 2 días autónomo.Ageing is a natural process associated with a decline that results in an increased risk of physical and cognitive disability and/or emotional and sentimental impairment. Consequently, several studies show the multiple benefits of multi-component training programmes. The current guidelines extend this approach to multi-domain programmes. For this reason, the objective of this paper is to present the Healthy-Age multi-domain intervention programme that follows the recommendations of the main institutions and scientific literature and includes the main domains (physical, social, cognitive and motivational) in older people. Its purpose is to prevent, maintain or improve the overall health (physical, psychological, emotional and social level) for a healthy ageing. In addition to including general recommendations of physical activity, recommendations are shown for aerobic resistance, balance, coordination, muscular strength and resistance, flexibility and cognitive training; and two modalities are presented; a 5-day supervised plan and a 3-day supervised plan plus 2 autonomous days.Consejo Superior de Deportes (CSD) del Ministerio de Cultura y Deporte del gobierno de España (06/ UPR/19 y 08/UPR/20

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.S