Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences ...chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as 'operational tolerance'. However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.
Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with ...sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.
Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme ...(TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is activated in response to elevated concentrations of extracellular ATP and induces different pro-inflammatory pathways in macrophages to establish an inflammatory response. P2X7 receptor promotes the activation of the inflammasome and the release of interleukin-1β, the production of inflammatory lipids, and the generation of reactive oxygen species. In this study, we analyzed the mechanism of P2X7 receptor responsible of TNF-α release after priming macrophages with LPS doses ≤100 ng/ml. We found that P2X7 receptor increases the extracellular activity of TACE through the release of the mature form of TACE in exosomes. This effect was blocked using P2X7 receptor inhibitors or in macrophages obtained from P2X7 receptor-deficient mice. Elevation of intracellular Ca
and p38 mitogen-activated protein kinase after P2X7 receptor activation were involved in the release of TACE, which was able to process TNF-α on nearby expressing cells. Finally, we observed an increase of TNF-α in the peritoneal lavage of mice treated with LPS and ATP. In conclusion, P2X7 receptor induces the release of TACE in exosomes to the extracellular compartment that could amplify the pro-inflammatory signal associated to this receptor. These results are important for the development of therapeutics targeting P2X7 receptor.
Introducción: Los factores psicosociales influyen en la calidad de vida de los profesionales de enfermería en el ámbito hospitalario asociados a variables sociodemográficas y laborales que repercuten ...en su calidad de vida.Objetivo: Analizar la calidad de vida laboral percibida por los profesionales de enfermería en un centro hospitalario, asociada a factores psicosociales y sociodemográficos.Metodología: Trabajo de campo descriptivo, observacional, cuantitativo, concurrente, transversal sobre calidad de vida. Muestra: profesionales de enfermería del ámbito hospitalario (N=240). El estudio realizado desde 2016 a 2018.Herramienta medición: cuestionario CVP-35, y datos sociodemográficos y laborales.Resultados: La satisfacción de los profesionales con la calidad de vida percibida (94%) es alta. Los porcentajes bajos se presentan en el apoyo directivo (48%). Existen asociaciones significativas (p<0.05) entre los ámbitos sociodemográficos y su relación con las tres dimensiones analizadas de la calidad de vida laboral.Conclusiones: El apoyo directivo hacia los enfermeros no ha sido un estímulo apropiado para el desarrollo y mejora de sus funciones.
RESUMEN Introducción La musicoterapia se entiende por el uso de la música o sus elementos con fines terapéuticos. Su empleo en la enfermería es escaso más allá del uso de la intervención NIC 4400. ...Objetivo Conocer y analizar el grado de aceptación por parte de los estudiantes de enfermería ante la posible inclusión de la musicoterapia como asignatura en los programas educativos de los estudios de Grado en Enfermería. Método Se ha realizado un estudio observacional descriptivo de corte transversal con una muestra n=346 participantes. Resultados Los resultados muestran que el 93,93% de los alumnos sí incluirían la musicoterapia como una asignatura Optativa en los estudios de Grado en Enfermería, haciendo uso de ella en su futuro profesional.
Introducción: La musicoterapia se entiende por el uso de la música o sus elementos con fines terapéuticos. Su empleo en la enfermería es escaso más allá del uso de la intervención NIC 4400. Objetivo: ...Conocer y analizar el grado de aceptación por parte de los estudiantes de enfermería ante la posible inclusión de la musicoterapia como asignatura en los programas educativos de los estudios de Grado en Enfermería. Método: Se ha realizado un estudio observacional descriptivo de corte transversal con una muestra n=346 participantes.Resultados: Los resultados muestran que el 93,93% de los alumnos sí incluirían la musicoterapia como una asignatura Optativa en los estudios de Grado en Enfermería, haciendo uso de ella en su futuro profesional.
Introduction: Music therapy is understood by the use of music or its elements for therapeutic purposes. Its use in nursing is scarce beyond the use of the NIC 4400 intervention. Objective:The research aims to know and analyze the degree of acceptance by nursing students regarding the possible inclusion of music therapy as a subject in the educational programs of the Nursing Degree studies.Method: A cross-sectional, observational, descriptive study was carried out with a sample of n=346 participants. Conclusion: The results show that 93.93% of the students did include music therapy as an optional subject in Nursing Degree studies, making use of it in their professional future.
Introduction
Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in ...transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice.
Objective
To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes.
Material and Methods
Type of study: A sociological, interdisciplinary, observational and multicentre study in Spain. Study population: Students enrolled on the medical degree in Spain (n = 34 000). Sample size: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID‐XenoTx RIOS) which was self‐administered and completed anonymously.
Results
A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005).
Conclusions
Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre‐clinical xenotransplantation programme and new healthcare centres.
Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic ...transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells. In human liver transplant patients undergoing progressive immunosuppressive drug withdrawal, we found that patients experiencing acute rejection had higher levels of the P2X7 receptor in circulating inflammatory monocytes compared to tolerant patients. These data suggest that the pharmacological inhibition of the P2X7 receptor or the NLRP3 inflammasome will aid in inducing transplant tolerance without complete immunoparalysis.
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•Extracellular ATP is an early danger signal associated with allotransplants•P2X7 receptor in macrophages is important for maintaining high extracellular ATP•P2X7 receptor activates NLRP3 inflammasome and IL-18 release in allotransplants•IL-18 is important to establish a correct adaptive alloimmune response
Amores-Iniesta et al. find that extracellular ATP is important in the establishment of allograft rejection during mismatched tissue transplantation through NLRP3 inflammasome activation and IL-18 production. The P2X7 receptor in macrophages helps to maintain high extracellular ATP levels in mismatched tissue grafts at early time points after transplantation.
Summary
The Latin American (LA) population has similarities with the Spanish population which makes its integration into Spanish society easier. Objective: to analyze the attitude toward organ ...donation among Latin American citizens residing in Spain, to determine the psychosocial variables which affect this attitude, and to examine the correlation between donation rates of LA citizens in Spain and in their countries of origin. A random sample of LA residents in Spain was taken and stratified according to the respondent's nationality (n = 1.314), in the year 2010. Attitude was assessed using a validated questionnaire (PCID‐DTO Dr Rios). The survey was self‐administered and completed anonymously. Statistical analysis: Student's t‐test, the χ2 test, and logistic regression analysis. There was a 94% completion rate (n = 1.237). Attitude toward donation was favorable in 60% of cases (n = 745), 12% (n = 145) were against, and 28% (n = 347) were undecided. The following variables were associated with attitude toward donation: sex (P = 0.038), level of formal education (P < 0.001), country of origin (P = 0.002), attitude toward the donation of a family member's organs (P < 0.001), having discussed donation with the family (P < 0.001), carrying out prosocial activities (P = 0.025), attitude toward cremation of the body (P < 0.001), attitude toward burial of the body (P < 0.001), attitude toward having an autopsy carried out (P < 0.001), previous experience of the organ donation and transplantation process (P < 0.001), fear of mutilation after donation (P < 0.001), knowledge that the Church has a positive attitude toward organ donation and transplantation (P < 0.001), knowledge of one's partner's attitude toward organ donation (P < 0.001), and a belief that one might need a transplant in the future (P < 0.001). The donation rates in this population group in Spain are higher than those recorded in their countries of origin (55.76 vs. <10 pmp; P < 0.001). The attitude toward organ donation among LA citizens residing in Spain is slightly worse than that reported in the native Spanish population and is determined by many psychosocial factors. The donation rates of LA citizens in Spain are higher than those in their countries of origin.
The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, ...respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39‐CD73‐A2R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.
Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of operational tolerance in liver transplantation.
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