Fibrosis hepática de origen incierto en pacientes infectados por el VIH: prevalencia y factores asociados

Introducción: Recientemente se han documentado en sujetos con infección por el VIH casos de fibrosis hepática, incluyendo la presencia de cirrosis descompensada, de causa desconocida. Esta entidad, que podríamos denominar fibrosis hepática de origen incierto (FHOI), es extremadamente infrecuente en la población general, con una tasa de prevalencia menor del 0.01%. Su prevalencia en pacientes infectados por el VIH se encuentra entre el 0.3-17%. Se ha sugerido que podría estar relacionado con una exposición prolongada al tratamiento con didanosina (ddI). El objetivo de nuestro estudio fue evaluar la prevalencia de FHOI en pacientes infectados por el VIH y analizar los factores asociados con la presencia de la misma. Material y métodos: Estudio transversal con análisis de casos y controles realizado en la Unidad de Enfermedades Infecciosas de dos hospitales universitarios de Andalucía. Se evaluó la presencia de FHOI mediante elastometría hepática transitoria [FibroScan, Echosens, Paris, France] en pacientes infectados por el VIH sin coinfección por VHB ó VHC, ni enfermedad autoinmune o metabólica conocidas. La existencia de una medida de fibrosis hepática ¿ 7,2 Kpa fue considerada significativa, valor que será tomado como indicativo de FHOI. Se realizaron análisis univariantes y una regresión logística múltiple para identificar los factores asociados a la variable primaria del estudio. Resultados: Veintinueve (11,2%) pacientes presentaron FHOI. En el análisis multivariante, el consumo diario de alcohol > 50 g, un recuento de CD4 < 200 cél/mL, el tiempo de tratamiento antirretroviral, la exposición reciente a ABC, el tiempo de exposición a ABC y el tiempo de exposición a ddI se asociaron de manera independiente con la presencia de FHOI. Conclusiones: La elastometría hepática transitoria determina la presencia de FHOI en pacientes infectados por el VIH. Esta entidad tiene una prevalencia del 11,1% en pacientes con infección por el VIH. El consumo de alcohol, la inmunosupresión, el tiempo de tratamiento antirretroviral y la exposición a fármacos antirretrovirales como abacavir o didanosina son factores asociados a esta condición

Characterization of plant growth promoting bacteria isolated from red fruits. Studies on growth promotion and fruit quality in strawberries plants

Microoganisms associated to the rizosphere of cultivated plants used for human consumption are scarcely analyzed. However, nowadays, organic farming, where the use of microbial inoculants is essential, has arisen as an emergent alternative with great commercial interest. In this study, a collection of bacterial strains isolated from strawberry and blueberry rhizosphere (healthy and infected with Macrophomina phaseolina) as well as from the inside of stolons of strawberries plants (endophytic bacteria) has been constructed and characterized by their PGP and biocontrol properties. Three PGP properties have been determinate: auxin and siderophores production and phosphate solubilization. Regarding biocontrol activities, the presence of five enzymatic activities have been determined: protease, chitinase, cellulose, amylase and β-Glucosidase. On the other hand, the ability of the isolated strains to inhibit under in vitro conditions the growth of two pathogenic fungi of rump fruits, TOR 102 and TOR 872 (both belonging to the specie M. phaseolina) was tested. Strains reaching the better results were sequenced and identified as: Cupriavidius metalliduras, Bacillus proteolyticus, Arthrobacter pascens, Bacillus amyloliquefaciens, Raoultella planticola, Enterobacter roggernkampii, Bacillus megaterium, Pseudomonas multiresinivorans, Bacillus invictae, Pseudomonas aeruginosa, Chryseobacterium cucumelis, Klebsiella pneumonia, Achromobacter denitrificans, Bacillus velezenvelezensis, Burkholdelia contaminans, Bacillus niacin, Pantoea annatis, and Bacillus frigoritolerans. After that, a strawberry growth promotion assay was performed under controlled conditions. Strawberries plants were inoculated with three bacterial strains previously characterized by its high level of auxin production, namely Enterobacter rooggenkampii (AC8), Chryseobacterium cucumelis (ACH2) and Klebsiella pneumoniae (ACH7t). A greenhouse assay was carried out, with 6 replicates per treatment, including three strains as well as an uninoculated control. Biometric parameters (flowering precocity, number and weight or fruits, root and shoot dry weight), as well as quality ones (fruit size and Brix degrees) were determined at the end of the assay. Results showed that strains ACH7t was significantly superior in flowering precocity and number of fruits, while strains AC8 and ACH7t showed Brix values significantly different than the other treatments

Introducción al análisis matemático mediado por las TICs

El presente documento es un avance del Proyecto “Propuesta curricular, con soporte en las NTIC, para favorecer el estudio independiente del Cálculo” aprobado por la Secretaría de Ciencia, Arte e Innovación Tecnológica de la Universidad Nacional de Tucumán y describe la experiencia de un aula virtual realizada por la cátedra de Matemática I (materia del Ciclo Básico) de la Facultad de Bioquímica, Química y Farmacia (FBQF), a través de la plataforma educativa Moodle 3.0 del Campus Virtual de la U.N.T. En este trabajo se exponen las ideas principales que sustentan una propuesta didáctica para el aprendizaje de los contenidos de Matemática I como recurso para mejorar la calidad del proceso de aprendizaje y formalizar la relación docente-alumno que actualmente existe a través de la cuenta de facebook: “Matemática Bioquímica”, utilizando Tecnologías de la Información y Comunicación. Para ello se planteó el diseño del aula en base a la extensión, estructura y profundidad de los contenidos. En esta ocasión se realizó una autoevaluación del tema “Límite de una Función” anterior al primer examen parcial y dos autoevaluaciones (teórica y práctica) que abarcaban todos los temas para el segundo examen parcial. Se tuvo especial cuidado que los mismos fueran significativos para los estudiantes y estén relacionados con situaciones de su interés.Eje 4: Implementación y usos de TIC's en aulaFacultad de Ciencias Exacta

Uso de un aula virtual como complemento en la enseñanza del tema límite de funciones

El presente documento es un avance del Proyecto “Propuesta curricular, con soporte en las NTIC, para favorecer el estudio independiente del Cálculo” aprobado por la Secretaría de Ciencia, Arte e Innovación Tecnológica de la Universidad Nacional de Tucumán y describe la experiencia de un aula virtual realizada por la cátedra de Matemática I (materia del Ciclo Básico) de la Facultad de Bioquímica, Química y Farmacia (FBQF), a través de la plataforma educativa Moodle 3.0 del Campus Virtual de la U.N.T. En este trabajo se exponen las ideas principales que sustentan una propuesta didáctica para el aprendizaje de los contenidos de Matemática I como recurso para mejorar la calidad del proceso de aprendizaje y formalizar la relación docente-alumno que actualmente existe a través de la cuenta de facebook: “Matemática Bioquímica”, utilizando Tecnologías de la Información y Comunicación. Para ello se planteó el diseño del aula en base a la extensión, estructura y profundidad de los contenidos. En esta ocasión se realizó una autoevaluación del tema “Límite de una Función” anterior al primer examen parcial y dos autoevaluaciones (teórica y práctica) que abarcaban todos los temas para el segundo examen parcial. Se tuvo especial cuidado que los mismos fueran significativos para los estudiantes y estén relacionados con situaciones de su interés.Eje 1: Innovación y exploración en cambios de modalidades en cursadasFacultad de Ciencias Exacta

Introducción al análisis matemático mediado por las TICs

El presente documento es un avance del Proyecto “Propuesta curricular, con soporte en las NTIC, para favorecer el estudio independiente del Cálculo” aprobado por la Secretaría de Ciencia, Arte e Innovación Tecnológica de la Universidad Nacional de Tucumán y describe la experiencia de un aula virtual realizada por la cátedra de Matemática I (materia del Ciclo Básico) de la Facultad de Bioquímica, Química y Farmacia (FBQF), a través de la plataforma educativa Moodle 3.0 del Campus Virtual de la U.N.T. En este trabajo se exponen las ideas principales que sustentan una propuesta didáctica para el aprendizaje de los contenidos de Matemática I como recurso para mejorar la calidad del proceso de aprendizaje y formalizar la relación docente-alumno que actualmente existe a través de la cuenta de facebook: “Matemática Bioquímica”, utilizando Tecnologías de la Información y Comunicación. Para ello se planteó el diseño del aula en base a la extensión, estructura y profundidad de los contenidos. En esta ocasión se realizó una autoevaluación del tema “Límite de una Función” anterior al primer examen parcial y dos autoevaluaciones (teórica y práctica) que abarcaban todos los temas para el segundo examen parcial. Se tuvo especial cuidado que los mismos fueran significativos para los estudiantes y estén relacionados con situaciones de su interés.Eje 4: Implementación y usos de TIC's en aulaFacultad de Ciencias Exacta

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score # 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.8 página

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

FUNDING. Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS. The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS. PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs. CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127, PI22/01796)Gilead Fellowships (GLD22/00147)NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHEBill and Melinda Gates Foundatio

Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes

[Background] Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors.[Methods] pDCs, CD4 and CD8 T-cells were isolated from 450 ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed.[Findings] pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC.[Interpretation] These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies.This work was supported by Gilead fellowship program (GLD17-00299), the Instituto de Salud Carlos III (ISCIII) and co-financed by the European Union, Fondos FEDER, “a way to make Europe” (research contracts CP19/00159 to AGV, FI17/00186 to MRJL, FI19/00083 to CGC, and research projects PI16/01684, PI19/01127 and PI22/01796) and the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020 and RD16/0025/0026 to E.R.M.), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016, Instituto de Salud Carlos III. ERM was granted by the Spanish National Research Council (CSIC).Peer reviewe

The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study

The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers