Impacto de la colonización respiratoria y de la bacteria asintomática sobre el riesgo de infección en candidatos a trasplante hepático y cardiaco

Existen pocas descripciones de la epidemiología de la infección en pacientes candidatos a trasplante hepático1, y ninguna de pacientes candidatos a trasplante cardíaco. Varios autores han demostrado como el desarrollo de infecciones en pacientes con hepatopatía o cardiopatía avanzada empeoran el pronóstico y son causa de una buena parte de los ingresos hospitalarios de estos pacientes2,3. Existen sin embargo estudios que no encuentran una asociación entre el desarrollo de infecciones previamente al trasplante y el pronóstico posterior 4. Así mismo, se desconoce el impacto clínico de los aislamientos microbiológicos bacterianos o fúngicos en muestras respiratorias o en urocultivos de pacientes asintomáticos con hepatopatía o cardiopatía avanzada. El aislamiento previo de algunos microorganismos como S.aureus en muestras procedentes de la vía respiratoria puede predecir una infección posterior por el mismo 5,6. Por este motivo, la erradicación de la colonización microbiológica mediante el empleo de un tratamiento antibiótico se ha planteado como una posible estrategia para reducir la incidencia de ciertos tipos de infección. Aunque se han desarrollado varios estudios en este sentido, los resultados han sido contradictorios 7,8,9. La presencia de bacteriuria asintomática se ha relacionado con un peor pronóstico en algunos subgrupos de pacientes cirróticos10. Sin embargo, el tratamiento de la bacteriuria asintomática sólo ha demostrado utilidad en ciertos subgrupos de población muy específicos, como mujeres embarazadas o pacientes que van a ser sometidos a una intervención urológica11. Recientemente se ha reevaluado la utilidad del tratamiento de la bacteriuria asintomática en pacientes trasplantados renales 12. No se ha evaluado el impacto o la utilidad del tratamiento de la bacteriuria asintomática en pacientes candidatos a trasplante cardíaco o hepático

Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

Gonadotropin-primed immature rats (GPIR) constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG) synthesis indomethacin (INDO) and a progesterone (P) receptor (PR) antagonist (RU486). Immature Wistar rats were primed with equine chorionic gonadotropin (eCG) at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG) 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC) was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age

Conservación y puesta en valor del yacimiento argárico de Castellón Alto (Galera, Granada)

The magnificent preservation of the archaeological site of Castellón Alto permitted reconstruction of the urbanism of this settlement and the life of its inhabitants. In addition to the necessary conservation, two interventions have been carried out with the principal objective of facilitating access, visiting, and the understanding of the site by the majority of the public. The first intervention happened in 1989 and the main task was centered on the consolidation, restoration, and delimiting of the archaeological bed. The second one happened in 1997 and was centered in the consolidation and reconstruction of both a hut and two tombs. With the opening of the Archaeological Museum of Galera, the cultural and touristic contribution of Castellón Alto will be complete. It will provide an interpretation of this prehistoric village, as well as the Argaric culture in general and all the other archaeological sites of the area.La magnífica conservación del registro arqueológico del Castellón Alto permitía reconstruir el urbanismo del poblado y la vida de estas poblaciones. Se han efectuado dos actuaciones con el objetivo principal de facilitar, además de la necesaria conservación, el acceso, la visita y la comprensión del poblado prehistórico por parte de un público mayoritario. La primera actuación se realizó en 1989 y los trabajos se centraron principalmente en la consolidación, restauración y cerramiento del área del yacimiento. La segunda se realizó en 1997 y se centró en el acondicionamiento y reconstrucción de una cabaña y dos sepulturas. La oferta turística y cultural que ofrece el Castellón Alto se completará con la próxima apertura del Museo Arqueológico de Galera, donde se efectuará una interpretación de este poblado y de la cultura argárica, así como del resto de yacimientos de la zona

Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8+ T Cells and Cytomegalovirus Replication after Transplantation

In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8+ T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer. A correlation between the proportion of CD28− HCMV-specific CD8+ T cells and age was observed in patients without HCMV replication (r = 0.50; P = 0.02) but not in patients with HCMV replication (r = −0.05; P = 0.83), a finding which differs from that observed for total CD8+ T cells. Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28− HCMV-specific CD8+ T cells (85.6 compared with 58.7% for patients without HCMV replication; P = 0.004) and CD27− HCMV-specific CD8+ T cells (90.7 compared with 68.8% for patients without HCMV replication; P = 0.03). However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28− HCMV-specific CD8+ T cells, 84.4 and 80.9%, respectively [P = 0.39]; for CD27− HCMV-specific CD8+ T cells 86.6 and 81.5%, respectively [P = 0.16]). In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27− and CD28− HCMV-specific CD8+ T cells. These results suggest that the increased percentage of CD27− or CD28− HCMV-specific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients. Further studies are necessary to define the significance of these changes in HCMV-associated clinical complications posttransplantation

Mutations related to Antiretroviral Resistance identified by ultra-deep sequencing in HIV-1 infected children under Structured Interruptions of HAART

Altres ajuts: CONACYT/GCPS/44519Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI

AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein–specific T H 1 response with a diverse TCR repertoire

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus–vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized CD4+ and CD8+ T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein–specific CD4+ T cell helper type 1 (TH1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages after two doses of AZD1222. CD4+ TH2 responses after AZD1222 vaccination were not detected. Furthermore, AZD1222-specific TH1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor β (TCRβ) sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4+ and CD8+ T cell responses. Overall, AZD1222 vaccination induced a polyfunctional TH1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein