Influencia de los estereotipos de género en los hombres profesionales de enfermería

Trabajo fin de grado en EnfermeríaObjetivo: Conocer cómo influyen los estereotipos de género en los varones enfermeros, dentro de una profesión considerada eminentemente femenina. Metodología: Se plantea una revisión narrativa mediante la búsqueda de información a través de las bases de datos de PubMed, Cuiden, Scielo, CINAHL, Cochrane, Repositorio de la Universidad de la Rioja (DIALNET), PscINFO y Google Scholar utilizando lenguaje libre y controlado con los diferentes tesauros, empleando los operadores booleanos AND, OR y NOT y truncamientos como enfermer *. La búsqueda se limitó a los últimos 5 años (2013-2018) y a los idiomas inglés, francés, portugués y español. Resultados: Se seleccionaron un total de 31 artículos cuya información se analiza en base a cuatro unidades de análisis: Factores facilitadores y disuasorios percibidos por los hombres en la enfermería; Conflicto de roles de género: construcción de la masculinidad; Interacción con los pacientes y establecimiento de la relación terapéutica e Interacción e integración en el equipo de profesionales. Discusión: Los hombres perciben tanto barreras para su desarrollo como enfermeros, como elementos positivos que condicionan su permanencia en la profesión. Algunos se enfrentan a un conflicto de roles entre la propia masculinidad y la profesión de Enfermería, considerada femenina, y desarrollan estrategias compensatorias. El sexo del profesional influye en la interacción con los pacientes y el establecimiento de la relación terapéutica, sobre todo con mujeres. Entre los profesionales existen diversos grados de aceptación de los enfermeros. Conclusiones: Los resultados orientan las próximas investigaciones hacia el conocimiento de la situación en Europa y el desarrollo de estrategias para el reclutamiento de más hombres en la Enfermería.Aim: Finding out the way gender stereotypes influence male nurses within a profession that´s essentialy directed to women. Methods: A narrative review was made with researches in the databases of PubMed, Cuiden, Scielo, CINAHL, Dialnet, PscINFO and Google Scholar. Free and controlled language were used in combination with the boolean operators AND, OR and NOT and the shortening *. The research was limited to 5 years (2013-2018) and to the languages of english, french, portuguese and spanish. Results: 31 articles were found whose information is analized according to four categories: enabling and detering factors viewed by men in nursing, gender role conflicts: construction of masculinity, interaction with patients and the establishment of the therapeutic relation and lastly the interaction and incorporation in the professional unit. Discussion: Men percieve multiple barriers when they have to study and develop nursing but there are also positive elements that condition their entry and continuity. Some nurses find themselves facing a conflict of roles between their own masculinity and this profession due to it being considered female and create compensating strategies. The sex of a professional influences their interactions with patients and difficults the establishment of the therapeutic relation specially when attending female population. Within professionals there is various degrees of acceptance of male nurses. Conclusions: Results of new investigations are directed to knowledge of Europe´s situation and the development of strategies for the recruitment of more men within the nursing profession

Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas

To evaluate the use of alphavirus vectors for tumor treatment we have constructed and compared two Semliki Forest virus (SFV) vectors expressing different levels of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed from an independent subgenomic promoter fused to the SFV capsid translation enhancer. This latter strategy provided an eightfold increase of IL-12 expression. We chose the poorly immunogenic MC38 colon adenocarcinoma model to evaluate the therapeutic potential of SFV vectors. A single intratumoral injection of 10(8) viral particles of SFV-IL-12 or SFV-enh-IL-12 induced>or=80% complete tumor regressions with long-term tumor-free survival. However, lower doses of SFV-enhIL-12 were more efficient than SFV-IL-12 in inducing antitumoral responses, indicating a positive correlation between the IL-12 expression level and the therapeutic effect. Moreover, repeated intratumoral injections of suboptimal doses of SFV-enhIL-12 increased the antitumoral response. In all cases SFV vectors were more efficient at eliminating tumors than a first-generation adenovirus vector expressing IL-12. In addition, the antitumoral effect of SFV vectors was only moderately affected by preimmunization of animals with high doses of SFV vectors. This antitumoral effect was produced, at least partially, by a potent CTL-mediated immune response

De novo transcriptome characterization of Ulva lacinulata under in situ emersion/immersion cyclic conditions.

The green algal genus Ulva Linnaeus (Ulvaceae, Ulvales, Chlorophyta) displays a worldwide distribution in marine, freshwater and brackish ecosystems, and are really well adapted to fluctuating natural environments. Despite increasing interest on the analysis of the ecophysiological responses showed by organisms to face environmental shifts, knowledge of the genetic and molecular mechanisms underlying those responses are still scarce. These responses determine the survival of organisms under pressure of different environmental stresses and the regular ecosystem behaviour. In order to disentangle the genetic networks that might regulate the adaptation mechanisms of these organisms in a changing environment, the characterization of the de novo transcriptome from Ulva lacinulata derived from a coastal ecosystems of southern Spain under in situ cyclic conditions of emersion/immersion by using Next Generation Sequencing technologies was carried out. Transcriptome sequencing and transcript-level expression analysis were performed by Illumina®NextSeq® 550 system platform. A total of 100,251 unigenes were expressed during emersion/immersion process. Based on the differentially expressed genes (DEGs), genes associated with different biosynthetic metabolic pathways were annotated according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Orthology (KEGG). These findings shed light on the molecular mechanisms underlying rapid and successful ecophysiological response of marine macroalgae in cyclic tidal conditions.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Transcriptomic effects of Tet-on and mifepristone-inducible systems in mouse liver

Control of transgene expression from long-term expression vectors can be achieved with inducible and regulated promoters. The two most commonly used inducible systems employ doxycycline or mifepristone as the drug activating a silent trans-activator, which is expressed from a constitutive promoter. We evaluated the alterations provoked by constitutive expression in the liver of rtTA2(S)-M2 (rtTA2; second-generation reverse tetracycline-controlled trans-activator) and GLp65, which are the trans-activators of the doxycyline- and mifepristone-inducible systems, respectively. To this end we performed transcriptomic analysis of mice expressing these trans-activators in the liver over 1 month. rtTA2 expression induced alterations in a few genes (69 gene probesets; false discovery rate [FDR], approximately 0.05), whereas GLp65 caused more numerous changes (1059 gene probe-sets, an FDR of approximately 0.05). However, only 20 and 53 of the genes from the rtTA2 and GLp65 groups, respectively, showed changes (R-fold >or= 3). Functional assignments indicate that alterations were mild and of little general significance. Few additional transcriptomic changes were observed when expressing trans-activators in the presence of inducer drugs; most were due to the drugs themselves. These results and the absence of toxicity observed in treated animals indicate that the two inducible systems are well tolerated and have little impact on the liver transcriptome profile. The milder alterations found with the use of rtTA2 suggest that this system is possibly safer for gene therapy application

Transcriptomic effects of Tet-on and mifepristone-inducible systems in mouse liver

Control of transgene expression from long-term expression vectors can be achieved with inducible and regulated promoters. The two most commonly used inducible systems employ doxycycline or mifepristone as the drug activating a silent trans-activator, which is expressed from a constitutive promoter. We evaluated the alterations provoked by constitutive expression in the liver of rtTA2(S)-M2 (rtTA2; second-generation reverse tetracycline-controlled trans-activator) and GLp65, which are the trans-activators of the doxycyline- and mifepristone-inducible systems, respectively. To this end we performed transcriptomic analysis of mice expressing these trans-activators in the liver over 1 month. rtTA2 expression induced alterations in a few genes (69 gene probesets; false discovery rate [FDR], approximately 0.05), whereas GLp65 caused more numerous changes (1059 gene probe-sets, an FDR of approximately 0.05). However, only 20 and 53 of the genes from the rtTA2 and GLp65 groups, respectively, showed changes (R-fold >or= 3). Functional assignments indicate that alterations were mild and of little general significance. Few additional transcriptomic changes were observed when expressing trans-activators in the presence of inducer drugs; most were due to the drugs themselves. These results and the absence of toxicity observed in treated animals indicate that the two inducible systems are well tolerated and have little impact on the liver transcriptome profile. The milder alterations found with the use of rtTA2 suggest that this system is possibly safer for gene therapy application

Quantification of pharmacokinetic profiles of PD-1/PD-L1 antibodies by validated ELISAs

Immunotherapy has changed the paradigm of cancer treatments. In this way, several combinatorial strategies based on monoclonal antibodies (mAb) such as anti (a)-PD-1 or anti (a)-PD-L1 are often reported to yield promising clinical benefits. However, the pharmacokinetic (PK) behavior of these mAbs is a critical issue that requires selective analytical techniques. Indeed, few publications report data on a-PD1/a-PD-L1 exposure and its relationship with therapeutic or toxic effects. In this regard, preclinical assays allow the time profiles of antibody plasma concentrations to be characterized rapidly and easily, which may help to increase PK knowledge. In this study, we have developed and validated two in-house ELISAs to quantify a-PD-1 and a-PD-L1 in plasma collected from tumor-bearing mice. The linear range for the a-PD-1 assay was 2.5–125 ng/mL and 0.11–3.125 ng/mL for the a-PD-L1 assay, whereas the intra-and inter-day precision was lower than 20% for both analytes. The PK characterization revealed a significant decrease in drug exposure after administration of multiple doses. Plasma half-life for a-PD-1 was slightly shorter (22.3 h) than for a-PD-L1 (46.7 h). To our knowledge, this is the first reported preclinical ELISA for these immune checkpoint inhibitors, which is sufficiently robust to be used in different preclinical models. These methods can help to understand the PK behavior of these antibodies under different scenarios and the relationship with response, thus guiding the choice of optimal doses in clinical settings

Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12

Intratumoral injection of Semliki Forest virus encoding interleukin-12 (SFV-IL-12) combines acute expression of IL-12 and stressful apoptosis of infected malignant cells. Agonist antibodies directed to costimulatory receptor CD137 (4-1BB) strongly amplify pre-existing cellular immune responses toward weak tumor antigens. In this study, we provide evidence for powerful synergistic effects of a combined strategy consisting of intratumoral injection of SFV-IL-12 and systemic delivery of agonist anti-CD137 monoclonal antibodies (mAbs), which was substantiated against poorly immunogenic B16 melanomas (B16-OVA and B16.F10) and TC-1 lung carcinomas. Effector CD8(β)(+) T cells were sufficient to mediate complete tumor eradications. Accordingly, there was an intensely synergistic in vivo enhancement of cytotoxic T lymphocytes (CTL)-mediated immunity against the tumor antigens OVA and tyrosine-related protein-2 (TRP-2). This train of phenomena led to long-lasting tumor-specific immunity against rechallenge, attained transient control of the progression of concomitant tumor lesions that were not directly treated with SFV-IL-12 and caused autoimmune vitiligo. Importantly, we found that SFV-IL-12 intratumoral injection induces bright expression of CD137 on most tumor-infiltrating CD8(+) T lymphocytes, thereby providing more abundant targets for the action of the agonist antibody. This efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-CD137 mAbs are already undergoing clinical trials and development of clinical-grade SFV-IL-12 vectors is in progress

Gene therapy for progressive familial intrahepatic cholestasis type 3 in a clinically relevant mouse model

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare monogenic disease caused by mutations in the ABCB4 gene, resulting in a reduction in biliary phosphatidylcholine. Reduced biliary phosphatidylcholine cannot counteract the detergent effects of bile salts, leading to cholestasis, cholangitis, cirrhosis and ultimately liver failure. Here, we report results from treating two- or five-week-old Abcb4-/- mice with an AAV vector expressing human ABCB4, resulting in significant decreases of PFIC3 disease biomarkers. All male mice achieved a sustained therapeutic effect up through 12 weeks, but the effect was achieved in only 50% of females. However, two-week-old females receiving a second inoculation three weeks later maintained the therapeutic effect. Upon sacrifice, markers of PFIC3 disease such as, hepatosplenomegaly, biliary phosphatidylcholine and liver histology were significantly improved. Thus, AAV-mediated gene therapy successfully prevented PFIC3 symptoms in a clinically relevant mouse model, representing a step forward in improving potential therapy options for PFIC3 patients

Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity

Immune checkpoint blockade using monoclonal antibodies (mAbs) able to block programmed death-1 (PD-1)/PD-L1 axis represents a promising treatment for cancer. However, it requires repetitive systemic administration of high mAbs doses, often leading to adverse effects. We generated a novel nanobody against PD-1 (Nb11) able to block PD-1/PD-L1 interaction for both mouse and human molecules. Nb11 was cloned into an adeno-associated virus (AAV) vector downstream of four different promoters (CMV, CAG, EF1α, and SFFV) and its expression was analyzed in cells from rodent (BHK) and human origin (Huh-7). Nb11 was expressed at high levels in vitro reaching 2–20 micrograms/mL with all promoters, except SFFV, which showed lower levels. Nb11 in vivo expression was evaluated in C57BL/6 mice after intravenous administration of AAV8 vectors. Nb11 serum levels increased steadily along time, reaching 1–3 microgram/mL two months post-treatment with the vector having the CAG promoter (AAV-CAG-Nb11), without evidence of toxicity. To test the antitumor potential of this vector, mice that received AAV-CAG-Nb11, or saline as control, were challenged with colon adenocarcinoma cells (MC38). AAV-CAG-Nb11 treatment prevented tumor formation in 30% of mice, significantly increasing survival. These data suggest that continuous expression of immunomodulatory nanobodies from long-term expression vectors could have antitumor effects with low toxicity