Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.
Introduction: Cardiac surgery may induce acute kidney injury and the need for renal replacement therapy. It is also associated with higher hospital costs, morbidity and mortality. The aims of this study were to investigate predictors of cardiac surgery associated acute kidney injury in our population and to determine the burden of acute kidney injury in elective cardiac surgery, evaluating the potential cost effectiveness of preventing it through the application of the Kidney Disease: Improving Global Outcomes bundle of care to high-risk patient groups identified by the [TIMP-2]x[IGFBP7] used as a screening test.Material and Methods: In a University Hospital single-center retrospective cohort study we analyzed a consecutive sample of adults who underwent elective cardiac surgery between January and March 2015. A total of 276 patients were admitted during the study period. Data from all patients was analyzed until hospital discharge or the patient’s death. The economic analysis was performed from the hospital costs’ perspective. Results: Cardiac surgery associated acute kidney injury occurred in 86 patients (31%). After adjustment, higher preoperative serum creatinine (mg/L, ORadj = 1.09; 95% CI: 1.01 – 1.17), lower preoperative hemoglobin (g/dL, ORadj = 0.79; 95% CI: 0.67 – 0.94), chronic systemic hypertension (ORadj = 5.00; 95% CI: 1.67 – 15.02), an increase in cardiopulmonary bypass time (min, ORadj = 1.01; 95% CI: 1.00 – 1.01) and perioperative use of sodium nitroprusside (ORadj = 6.33; 95% CI: 1.80 – 22.28) remained significantly associated with cardiac surgery related acute kidney injury. The expected cumulative surplus cost for the hospital linked with cardiac surgery associated acute kidney injury (86 patients) was €120 695.84. Based on a median absolute risk reduction of 16.6%, by dosing kidney damage biomarkers in every patient and using preventive measures in high-risk patients, we would expect a break-even point upon screening 78 patients, which would translate, in our patient cohort, into an overall cost benefit of €7145.Conclusion: Preoperative hemoglobin, serum creatinine, systemic hypertension, cardiopulmonary bypass time and perioperative use of sodium nitroprusside were independent predictors of cardiac surgery associated acute kidney injury. Our cost-effectiveness modelling suggests that the use of kidney structural damage biomarkers combined with an early prevention strategy could be associated with potential cost savings.
This work has as main objective to analyze the use of the Narrative Imperfect in European Portuguese, in order to verify if this use is present in the language. The analysis is based on data collected from a Portuguese language repository, CETEMPúblico. The study focuses on constructions, where the Imperfect Tense is found in order to verify to what extent European Portuguese presents or not occurrences of the Narrative Imperfect. After analyzing the data collected, it was observed that there are some occurrences, based on two of the aspectual classes with which the Imperfect Tense is combined.
Este trabalho tem como principal objetivo analisar o uso do pretérito imperfeito do indicativo em duas línguas românicas, o português europeu e o espanhol europeu, de modo a verificar se os seus usos, em determinados contextos, são equivalentes ou distintos. A análise baseia-se em dados recolhidos em dois repositórios linguísticos, um português (CETEMPúblico) e outro espanhol (CREA), assim como em jornais online portugueses e espanhóis. O estudo centra-se em construções condicionais com o intuito de verificar até que ponto as duas línguas convergem ou não quanto ao uso do imperfeito nestas construções. Depois da análise dos dados, observou-se que há algumas diferenças entre as duas línguas nestas construções, tendo por base as classes aspetuais com as quais o pretérito imperfeito se combina.
We have systematically shown that the Amastigote Surface Protein-2 (ASP-2) and Transialidase (TS) antigens either in the form of recombinant protein or encoded in the plasmids and human adenovirus 5 (hAd5) confer strong protection against different lineages of Trypanosoma cruzi parasites. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from ASP-2 and TS (DTT-1) and evaluated its efficacy in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Our results show that mice immunized with DTT-1 protein together with Poly-ICLC (Hiltonol) become highly resistant to challenge with the Y strain of T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization and an equivalent level of protection induced by the DNA/hAd5 protocol. DTT-1 induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was mediated by B lymphocytes, CD8 T cells and IFNγ. Finally, we evaluated the toxicity, immunogenicity and efficacy of the DTT-1 and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated to Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine formulations protected dogs against challenge with the Berenice strain of T. cruzi. Despite to the similar efficacy, we conclude that moving ahead with DTT-1 together with Hiltonol is advantageous over the hAd5 vaccine due to the cost-benefit for development and large-scale production.
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