Synthesis of pyrazoline fatty chain derivatives and its effects on melanoma cells.

Skin cancer is the most common type of cancer in Brazil, representing 30% of all cases. Among these, melanoma represents only 3% of malignant neoplasms; however, it is the most serious and has a high capacity for metastasis. For this reason, it is extremely important to identify more efficient compounds and treatments that stop or decrease the proliferation of melanoma, even in its more advanced stages. This work reports the synthesis and biological evaluation of two homologous series of pyrazoline fatty chain derivatives as potent antitumoral agents in the melanoma B16F10 cell line. Cells were treated with pyrazoline fatty chain compounds (3, 30, 300, and 3000 µM) for 0, 24, 48, and 72 h. Decreased cell viability was observed when using most compounds at different concentrations and times. The structure-activity relationship (SAR) between antitumoral activity and the number of carbons and lipophilicity, as well as the oxygen-sulfur bioisosteric exchange, was evaluated. Among the tested derivatives, the lipophilic compounds 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-carboxamide (2d) and 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide (3d) showed the best results in the B16F10 cell line, as they produced the best cell viability decrease effects. The presence of fatty unbranched undecyl chain in the molecular structure appears to be important for its antimelanoma properties.

Variaciones de los tiempos de reacción frente a cambios de perspectiva y tamaño de los estímulos 2D y 3D en atención selectiva / RVariations of reaction times explained by stimuli changes in size and perspective in 2D and 3D for selective attention

Resumen Frente a un estímulo objetivo, las personas procesan mediante la atención selectiva antes de realizar toma de decisiones. Si ese estímulo sufre algún cambio en su configuración 2D o 3D, ¿en qué casos una persona reacciona más rápido o más lento? La presente investigación evaluó la influencia de los cambios en las características de los estímulos en experimentos de tiempos de reacción en tareas de atención visual en videojuegos creados en Unity 3D. Para estudiar esas características, se realizó una comparación entre dos experimentos de videojuegos. El primer experimento se dividió en dos bloques: uno mostraba estímulos en 2D y otro en 3D. Se recolectó el tiempo de reacción de los participantes frente a esos estímulos y se obtuvo que el tiempo de reacción fue mayor en 3D en 28.33 ms. En el segundo experimento se incrementaron los bloques (de dos a ocho) para explicar las diferencias de los tiempos de reacción obtenidas en el primer experimento sea por el tamaño o el ángulo relativo que otorga una diferente perspectiva geométrica de presentación de los estímulos en 3D, para lo cual se modificaron algunas características de los estímulos del primer experimento. Los resultados después de comparar los distintos escenarios muestran que la modificación de las características tiene una influencia en la atención selectiva, pues los tiempos de reacción del primer experimento varían en comparación a los del segundo experimento dependiendo del cambio realizado (entre 65 y 67 ms de diferencia para 2D y entre 53 y 77 ms para 3D). En la discusión, se analiza el ámbito de los estímulos en 2D y 3D en el neuromarketing o el deporte ante los cambios de tamaño y ángulo de la cámara. En ambos escenarios, el presente trabajo sugiere evaluar para cada caso la modificación en sus presentaciones o herramientas en un consiguiente incremento del tiempo de reacción de los potenciales usuarios o equivalentemente en un nivel bajo de atención.

Abstract When facing a goal-stimulus, people have a certain degree of attention. Therefore, when stimulus has changes in 2D or 3D configuration, in which cases one would react faster or slower? The present research evaluated the influence of the changes in the characteristics of the stimuli in reaction time experiments in visual attention tasks in videogames made in Unity 3D. For this, a comparison was made between two videogame experiments. The first videogame experiment was divided into two blocks that showed stimuli a block in 2D videogame and another in 3D videogame respectively to the participants and collected their reaction times against these stimuli. The second videogame experiment increase the number of blocks (from two to eight) to explain the differences in the reaction times obtained in the first experiment either by the size or the relative angle of 3D presentation of the stimuli, for which some characteristics of the blocks of the first experiment. The results, after comparing the different scenarios, have shown that the modification of the characteristics changed selective attention, because the reaction times of the first experiment vary in comparison to those of the second experiment depending on the change made (between 65 and 67 ms of difference for 2D and between 53 and 77 ms for 3D). On the discussion, one can question the commercial spheres of 2D stimuli in the so-called neuromarketing or sports. In both scenarios, the present work suggests evaluating for each case changes in their presentations or tools in a consequent control the reaction time of potential users, and this translates into a level of attention control.

Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis / Proteína EN2 urinária no diagnóstico do câncer de próstata: revisão sistemática e metanálise

Summary Introduction: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. Objective: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. Method: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. Results: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). Conclusion: The EN2 test showed high specificity (89%) and low sensitivity (66%).

Resumo Introdução: O câncer de próstata é o segundo tipo de câncer diagnosticado e a quinta causa de morte em homens em todo o mundo. O diagnóstico precoce é fundamental para o prognóstico da doença. Atualmente, o antígeno específico da próstata (PSA) é o biomarcador mais utilizado; porém, biomarcadores mais específicos devem ser estudados. Objetivo: Avaliar a acurácia da proteína engrenada-2 (EN2) na urina como biomarcador de câncer de próstata. Método: Foi realizada uma busca abrangente no período de janeiro de 2005 a julho de 2016, utilizando as seguintes bases de dados eletrônicas: Medline (PubMed), Embase, Cochrane Library e Lilacs. As palavras-chave utilizadas foram: "engrailed-2", "EN2", "prostatic neoplasms". A busca foi limitada a humanos e não houve restrição de idioma. A avaliação da qualidade dos estudos incluídos foi realizada de acordo com Quadas-2. A análise estatística foi realizada usando o software Meta-DiSc® e RevMan 5.3. Resultados: Foram identificados 248 estudos. Após a triagem dos títulos e resumos, foram excluídos 231. Um total de 17 foram lidos na íntegra e dois, incluídos na metanálise. A sensibilidade combinada foi de 66% (IC95% 0,56-0,75). A especificidade foi de 89% (IC95% 0,86-0,92). O DOR foi de 15,08 (IC95% 8,43-26,97). Conclusão: O teste EN2 mostrou alta especificidade (89%) e baixa sensibilidade (66%).

Development of an experimental model of portal vein ligation associated with parenchymal transection (ALPPS) in rats.

BACKGROUND: Liver failure might be a cause of death after major hepatectomies. The ALPPS technique appears to be a promising strategy to avoid it, however no experimental studies supporting this procedure have been previously described. The aim was to develop an experimental model of ALPPS in rats. METHOD: Experimental. A total of 30 Sprague Dawley rats were used. To develop the ALPPS procedure, ligation of the left portal branch of the middle lobe (LM) was performed. This demarcates the left side (SILM) from the right side (SDLM); parenchyma transection was performed following the demarcated line. The animal's weight, volume and weight of both LM were analyzed. Sacrifice at 3, 7 and 14 days after the procedure (10 per group) was performed. RESULTS: No bleeding or ascites were observed during the postoperative period. The LM increased by 24.1, 86.9 and 120.4% at 3, 7 and 14 days. The SDLM increased by 34.4, 78.8 and 102.0% at 3, 7 and 14 days. The SILM decreased 42.6, 64.8, and 79.3% at day 3, 7 and 14 days respectively. CONCLUSION: The ALPPS procedure can be performed in rats, achieving the expected results. Comparison studies to 2 staged hepatectomy will be necessary.

Dental developmental abnormalities in a patient with subtelomeric 7q36 deletion syndrome may confirm a novel role for the SHH gene.

Studies in mice demonstrated that the Shh gene is crucial for normal development of both incisors and molars, causing a severe retardation in tooth growth, which leads to abnormal placement of the tooth in the jaw and disrupted tooth morphogenesis. In humans the SHH gene is located on chromosome 7q36. Defects in its protein or signaling pathway may cause holoprosencephaly spectrum, a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres and that can be manifested in microforms such as single maxillary central incisor. A novel role for this gene in the developing human primary dentition was recently demonstrated. We report a 12-year old boy with a de novo 7q36.1-qter deletion characterized by high-resolution karyotyping, oligonucleotide aCGH and FISH. His phenotype includes intellectual disability, non-verbal communication, hypospadia, partial sacral agenesis and absence of coccyx, which are distinctive features of the syndrome and mainly correlated with the MNX1, HTR5A and EN2 genes. No microforms of holoprosencephaly spectrum were observed; but the patient had diastema and dental developmental abnormalities, such as conical, asymmetric and tapered inferior central incisors. The dental anomalies are reported herein for the first time in subtelomeric 7q36 deletion syndrome and may confirm clinically a novel role for the SHH gene in dental development.