A

Abstract:  Pancreatic ductal adenocarcinoma (PDCA) is one of the most aggressive and lethal cancers in the western world with a very poor survival. A characteristic pathway in the initiation of PDAC is the activation of the lipid-modified Sonic Hedgehog (SHH) ligand. Polyunsaturated fatty acids (PUFAs) are natural ligands of the transcription factor Gamma Peroxisome Proliferator Activated Receptor (PPARγ), which is also key to the SHH metabolic network. However, it is unknown how PUFAs regulate the SHH signaling pathway and PPARγ involved in the development of PDAC. Here we evaluated the effect of ω-3 and ω-6 PUFAs on SHH and PPARγ activation on tumor progression employing the human pancreatic cancer line PANC-1 in-vitro and in KPC knock-in transgenic mice in-vivo. PANC-1 cells were treated with PUFAs: arachidonic acid (ω-6, AA), eicosapentaenoic acid (ω-3, EPA) or docosahexaenoic acid (ω-3, DHA). Animals were fed with a semisynthetic diet with corn oil (ω-6) or fish oil (ω-3). The mRNA was analyzed by qPCR, proteins by Western Blot and cell viability of PANC-1 by Resazurin. Gas Chromatography was used to analyze the PUFAs profile of the PANC-1 cells and KPC mice tumors. Tumor volume was measured using a caliper, the fibrotic index by histologic assessment (Masson staining) and SHH by Immunochemistry. Data were analyzed by ANOVA. In PANC-1 cells the results showed that DHA reduced SHH gene and protein expression, increased PPARγ expression levels (p<0.05) and reduced cell viability in a dose-dependent manner (p<0.0001). Membrane lipid profile in PANC-1 and in KPC tumor cells correlated with pure and dietary PUFAs treatment respectively. The ω-3 significantly reduced tumor size (p<0.05), stromal desmoplasia (p<0.01) and SHH expression (p<0.05). The data obtained demonstrate that ω-3 PUFAs could modulate pancreatic tumor progression through PPARγ activation and SHH regulation promoting changes in the tissue environment affecting tumor growth.Resumen:  El adenocarcinoma de páncreas ductal (ACPD) es uno de los cánceres más mortales entre todas las neoplasias del mundo occidental con escasa sobrevida. Una vía característica en la iniciación de ACPD es la activación del ligando Sonic Hedgehog (SHH), modificado por lipidos. Los ácidos grasos poliinsaturados (AGPs)  también son ligandos naturales del factor de transcripción Receptor Gama Activado por Proliferadores de Peroxisomas gama (PPARγ) que además, es clave de la red metabólica de SHH. Sin embargo se desconoce como los AGPs regulan la vía de señalización de SHH y el factor PPARγ involucrados en el desarrollo del ACPD. Aquí evaluamos el efecto de AGPs ω-3 y ω-6 sobre la activación de SHH y PPARγ en la progresión tumoral empleando la línea de cáncer pancreático humano PANC-1 in-vitro y en ratones transgénicos knock-in KPC in-vivo. Las PANC-1 fueron tratadas con  AGPs: ácido araquidónico (ω-6, AA), ácido eicosapentanoico (ω-3, EPA) o ácido docosahexaenoico (ω-3, DHA). Los animales fueron alimentados con una dieta semisintética con aceite de maíz (ω-6) o aceite de pescado (ω-3). Se analizó el  ARNm por qPCR,  las proteinas por Western Blot y la viabilidad en PANC-1 mediante Resazurina. Se analizaron los datos por ANOVA.  En PANC-1 y en tumores de ratones KPC se evaluó el perfil de AGPs por cromatografía gaseosa. Se analizó el volumen tumoral usando calimetro, el índice fibrótico en cortes histológicos (tinción Masson) y SHH por Inmunohistoquimica. Los resultados indicaron que en PANC-1, el DHA redujo la expresión génica  y proteica de  SHH, incrementó los niveles de expresión de PPARγ  (p<0.05) y redujo la viabilidad celular de manera dosis-dependiente (p<0.0001). El perfil lipídico de membranas en PANC-1 y células tumorales KPC se correlacionó con  el tratamiento de AGPs puros y dietarios respectivamente. Los ω-3 redujeron significativamente el tamaño tumoral (p<0.0452), la desmoplasia estromal (p<0.0082) y la expresión de SHH (p<0.0433). Los datos obtenidos demuestran que los AGPs ω-3 podrían modular la progresión tumoral pancreática a través de la activación de PPARγ y de la regulación de SHH promoviendo cambios en el ambiente tisular afectando el crecimiento tumoral.

A Reescrita do riso: uma abordagem crítica de duas traduções portuguesas da obra The Importance of Being Earnest

Orientadora: Mestre Maria Helena GuimarãesO objectivo deste nosso trabalho é identificar, através de uma abordagem crítica de duas das traduções portuguesas da obra de Oscar Wilde The Importance of Being Earnest, quais os processos de fabricação do cómico, para utilizar aqui uma terminologia bergsoniana, bem como tentar sistematizar alguns dos problemas que a sua tradução coloca e apontar para estratégias que ajudem a solucionar as múltiplas dificuldades tradutivas presentes em textos marcados pela ironia e pelo humor. Cremos poder afirmar que as questões inerentes à tradução do Riso, do que de humorístico há num texto, escrito ou oral, raramente são abordadas pelos teóricos dos Estudos de Tradução, embora seja indiscutível o ser humor um fenómeno transversal a todas as culturas e os textos de cariz jocoso serem, em geral, bastante apreciados. Partimos deste pressuposto para estabelecer quer o nosso corpus de análise, quer a organização do nosso trabalho. A nossa investigação recairá, como já dissemos, sobre duas das traduções portuguesas existentes da obra de Oscar Wilde The Importance of Being Earnest, uma obra exemplar em termos da complexidade de interpretação e de tradução do humor, a saber: A Importância de Ser Earnest de Januário Leite1 Quanto Importa Ser Leal de António Pedro2 No Capítulo 2, socorrer-nos-emos das obras Le Rire, de Henri Bergson, e The Joke and its Relation to the Unconscious, de Sigmund Freud, para tentar chegar a uma definição do conceito de humor. No Capítulo 3, traçamos o quadro metodológico transdisciplinar que norteou este nosso trabalho de investigação. No Capítulo 4, tentaremos, com base na análise crítica comparada de duas traduções da peça de Oscar Wilde, The Importance of Being Earnest, apontar, pela via transdisciplinar, aqueles que consideramos ser os maiores obstáculos a uma correcta tradução do risível

Self-confidence for emergency intervention: adaptation and cultural validation of the Self-confidence Scale in nursing students

Objective: develop the cultural adaptation and validation of a Portuguese version of the Self-confidence Scale.Method: descriptive and exploratory methodological research for the adaptation and validation of a measuring instrument. The translation, synthesis, back-translation, revision, pretest and semantic evaluation phases were accomplished. The evaluation involving 178 students from a Teaching Diploma Program in Nursing. The ethical principles were complied with.Results: the internal consistency analysis of the scale reveals good Alpha coefficients (0.92 for the global scale and superior to 0.83 for the different dimensions). The factor analysis presents a three-factor solution with rational meaning.Conclusion: The scale is easy to answer and understand. Based on the obtained results, it can be affirmed that the scale reveals good psychometric properties, with great potential to be used in future research

Development of a theoretical-practical script for clinical simulation

Abstract OBJECTIVE To develop a theoretical-practical script based on the opinion of experts to be used in simulated clinical activities. METHOD Qualitative study through analysis of content of interviews with experts on the theme in order to develop the proposed script. Of the 24 invited experts, 12 specialists from educational institutions in Brazil and abroad participated in the study in compliance with the ethical precepts. The experts responded to questions on the characterization of their study attributes and described the items required for the development of a simulated scenario. In view of the responses obtained, data content was analyzed and classified into units and subunits of significance. RESULTS The items mentioned for the development of the script generated seven units of significance. The units and subunits of significance were gathered in three stages of the main components of the simulated scenario: prior, preparation, and finals. CONCLUSION This study enables an innovative, stimulating teaching experience, making it easier for professors to use the simulation resource as a learning process in an effective and objective manner, as a guide to professors and researchers in the area of clinical simulation

Sexual Functioning and Opioid Maintenance Treatment in Women. Results From a Large Multicentre Study

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation

Comparison of the antibacterial activity and synergistic activity towards antibiotics of different mammalian sera

The antibacterial activity against Escherichia coli ATCC 10798 and Staphylococcus aureus Mag 90 of normal sera from nine species of mammals was investigated by Avantage (Abbott). Human and rat sera showed the highest antibacterial activity against E. coli ATCC 10798, while all investigated sera did not exhibit, till the maximum concentration tested (20%), spontaneous antibacterial activity against S. aureus Mag 90. Heat inactivated sera (56 degrees C for 30 min) of all investigated species lost their antibacterial activity, but maintained their synergistic effect with sub-MICs of some antibacterial drugs, principally against E. coli ATCC 10798

Study on the bactericidal activity and synergistic effect of neutropenic rat serum with gentamicin

It is well known that normal rat serum (NRS) shows an antibacterial activity because of the presence of endogenous substances that are able to express a defence against pathogenic microorganisms. Moreover, in former studies, we observed that NRS presents a synergistic activity with some antibiotics (thus able to lower minimum inhibitory concentration values). The aim of this research was to study the antibacterial activity and synergistic effect of neutropenic rat sera (NPRS) with gentamicin. The animals were made neutropenic by the i.p. injection of cyclophosphamide (100 mg/kg on day 0 and 75 mg on day 4). At all tested concentrations (from 0.25% to 5%) NPRS showed lower antibacterial activity than NRS with differences which were always statistically significant. The synergistic activity of NPRS with gentamicin was still present and quite similar to that of NRS, in spite of many altered blood parameters showing evident immunodepression. Some possible interpretations of these results are discussed