Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Trends of mortality due to oral and oropharyngeal cancers in Uruguay from 1997 to 2014.

BACKGROUND: To analyze the trends of oral and oropharyngeal cancer mortality in Uruguay between 1997 and 2014 according to sex and age groups and its possible association with sociodemographic factors. MATERIAL AND METHODS: A time-series ecological study using secondary data was performed. The data about mortality due to oral and oropharyngeal cancers were obtained from the Statistics Vitals Department of the Public Health Ministry of Uruguay. To estimate the mortality trends of the historical series, by sex, anatomical site and age groups, linear regressions generated by the Prais-Winsten procedure were used. RESULTS: The analysis of mortality trends for oral cavity and oropharyngeal cancers in Uruguay indicated that the global mortality rate was stable over the studied period. The women's mortality rate increased from 0.51 per 100,000 in 1997 to 0.65 per 100,000 in 2014 while for men, rates per 100,000 went from 3.22 in 1997 to 2.20 per 100,000 in 2014. Mortality from oral cancer in men decreased between 1997 and 2014. Mortality by oropharyngeal cancer, irrespective of sex, remained stable. Analysis by cancer site revealed decreasing trends tumors situated in the base of the tongue and gum. Years of education, unemployment, smoking and Gini index were not associated with mortality trends. CONCLUSIONS: The overall mortality from oral and oropharyngeal cancer in Uruguay has remained constant in the period between 1997 and 2014. Oral cancer mortality decreased in men and increased in women and decreased at the base of the tongue. It's necessary to continue monitoring the behavior of these diseases.

MDGC-MS analysis of essential oils from Protium heptaphyllum (Aubl. ) and their antifungal activity against Candida specie / Análise MDGC-MS de óleos essenciais de Protium heptaphyllum (Aubl. ) e sua atividade antifúngica contra espécies de Candida

ABSTRACT Protium heptaphyllum is found in the Amazon region, and in various Brazilian states and South American countries. Also Known as almecega, it produces an oil resin used in traditional medicine as analgesic, anti-inflammatory, cicatrizant and expectorant, it is rich in pentacyclic triterpenes and essential oil. The main objective of this study was to analyze the chemical composition of P. heptaphyllumresin (OEPh) over different extraction times and to evaluate their antifungal activity against Candida species, obtained from gardeners with onychomycosis, using the disk diffusion method. The OEPh was obtained by hydrodistillation and analyzed by Multidimensional Gas Chromatography coupled with Mass Spectrometry (MDGC / MS). Candida species were obtained from lesions on the nails of horticulturist from a community garden in the city of Teresina, Piauí, Brazil. The antifungal activity in concentrations of 1000 µg/L, 500 µg/L and 250 µg/L, PROTOCOL M44-A2 (CLSI 2009) OEPh was tested. The main constituents identified were: l-limonene, α-terpineol, p-cineol, o-cymene and α-phellandrene, however, its composition varies significantly with extraction time. All species, except C. rugosa, were inhibited with halo (≥ 14 mm) at 1000 μg / L. C. krusei is naturally resistant to the drug fluconazole, but when tested with OEPh the clinical species (case 9) demonstrated sensitivity in three dilutions (halo ≤ 10 ≥ 14) and the standard strain was inhibited at concentration of 1000 μg/Lg / L (halo 14mm). A similar situation also occurred with the standard strain of C. parapsilosis (halo ≥ 11mm). OEPh has considerable antifungal activity, which merits further investigation for alternative clinical applications, since this species is widely distributed in our community, and it presents good yields, and also has important therapeutic applications.

RESUMO Protium heptaphyllum é encontrada na região amazônica, em vários estados do Brasil e países da América do Sul. Conhecida como almecega produz uma resina oleosa usada na medicina popular como analgésica, antiinflamatória, cicatrizante e expectorante, é rica em triterpenos pentaciclicos e óleo essencial. O objetivo principal do presente trabalho foi analisar a composição química do óleo essencial da resina P. heptaphyllum (OEPh) em diferentes tempo de extração e avaliarsuaatividade antifúngica contra espécies de Candida, isoladas de horticultores com onicomicoses, por método de disco-difusão. O OEPh foi obtido por hidrodestilação, analisado por Cromatografia Gasosa Multidimensinal Acoplada a Espectrometria de Massas (MDGC/MS). As espécies de Candida foram obtidas de lesões nas unhas de horticultores de uma horta comunitária na cidade de Teresina, Piauí, Brasil. Testou-se a atividade antifúngica do OEPhnas concentrações de 1000 μg/L, 500 μg/L e 250 μg/L, protocolo M44-A2 (CLSI 2009). Os principais constituintes identificados foram l- limoneno, α-terpineol, p-cineol, o-cimeno e α-felandreno, entretanto, sua composição varia significativamente em decorrência do tempo de extração. Todas as espécies, exceto a C. rugosa, foram inibidas com halo ( Χ ≥ 14 mm) na concentração de 1000 μg/L. C. krusei é naturalmente resistente ao fármaco fluconazol, mas quando testado com OEPh,a espécie clínico (caso 9) demonstrou sensibilidade nas três diluições (halo Χ ≤ 10 ≥ 14) e a cepa padrão foi inibida na concentração de 1000 μg/L (halo Χ 14mm). Fato semelhante também ocorreu com a cepa padrão de C. parapsilosis (halo Χ ≥ 11mm). O OEPh possui atividade antifúngica considerável, merecendo uma investigação mais aprofundada para aplicações clínicas alternativas, uma vez que esta espécie é amplamente distribuída em nossa comunidade, apresenta bom rendimento e, ainda, aplicações terapêuticas importantes.

Efeito de fungos micorrízicos arbusculares na bioprodução de fenóis totais e no crescimento de Passiflora alata Curtis / Total phenols in Passiflora alata Curtis inoculated with mycorrhizal fungi

Os compostos fenólicos encontrados no extrato das folhas de maracujazeiro doce (Passiflora alata Curtis) são os principais responsáveis pelos efeitos terapêuticos, incluindo a atividade ansiolítica. O presente trabalho avaliou o efeito de diferentes espécies de fungo micorrízicos arbusculares (FMAs) e doses de fósforo sobre a bioprodução de fenóis totais, bem como, o crescimento vegetal e os conteúdos de nitrogênio, fósforo e potássio na massa da matéria seca da parte aérea do maracujazeiro doce. O experimento, fatorial 4x2, foi conduzido em um telado com quatro tratamentos microbiológicos: Glomus etunicatum, Glomus intraradices, inóculo misto (Glomus clarum e Gigaspora margarita) e o controle sem fungo, e duas doses de fósforo: 0 e 50 mg kg-1 de solo. O delineamento experimental foi de blocos casualizados com quatro repetições. As plantas foram colhidas 90 dias após a semeadura. Na ausência da adubação fosfatada, o conteúdo de fenóis totais, a massa da matéria seca da parte aérea e o número de folhas foram maiores nos tratamentos inoculados com FMAs, quando comparados ao tratamento sem fungo. Plantas com inóculo misto apresentaram maior altura com ou sem adubação fosfatada. Os tratamentos inoculados com FMAs, tanto na dose 0 quanto na dose 50 mg kg-1 de P incrementaram os conteúdos de N, P e K na parte aérea do maracujazeiro doce, evidenciando a capacidade dos FMAs em promover o melhor estado nutricional das plantas.

The phenolic compounds found in extracts from leaves of sweet passion fruit (Passiflora alata) are mainly responsible for its therapeutic effects, such as the anxiolytic activity. This study evaluated the effects of different species of mycorrhizal fungi (AMF) and phosphorus levels on the bioproduction of total phenols, as well as plant growth and the contents of nitrogen, phosphorus and potassium in the dry mass of shoots of sweet passion fruit. The experiment was conducted in a greenhouse. The factors were arranged in a :[(microbiological treatments: Glomus etunicatum, Glomus intraradices, mixed inoculum (Glomus clarum and Gigaspora margarita) and without fungus] x 2 (doses of phosphorus: 0 and 50 mg kg-1 soil) factorial arrangement, in a randomized block experimental design with four replications. The plants were harvested 90 days after seeding. In the absence of phosphate fertilization, the total phenol content, dry mass of shoot and leaf number were greater in treatments inoculated with AMF compared to the treatments without fungus. Mixed inoculum plants had higher plant height with or without phosphate fertilization. Treatments inoculated with AMF in both the 0 and 50 mg kg-1 doses of P increased the content of N, P and K in the shoots of sweet passion fruit, demonstrating the ability of AMF to promote better nutritional statusfin plants.

PAS-1, an Ascaris suum Protein, Modulates Allergic Airway Inflammation via CD8+ ãäTCR+ and CD4+ CD25+ FoxP3+ T Cells

We have previously demonstrated that PAS-1, a 200 kDa protein from Ascaris suum, has a potent immunomodulatory effect on humoral and cell-mediated responses induced by APAS-3 (an allergenic protein from A. suum) or unrelated antigens. In this study, we investigated the mechanisms by which PAS-1 is able to induce this effect on an allergic airway inflammation induced by OVA in mice. C57BL/6 mice were adoptively transferred on day 0 with seven different PAS-1-primed cell populations: PAS-1-primed CD19+ or B220+ or CD3+ or CD4+ or CD8+ or CD4+ CD25- or CD4+ CD25+ lymphocytes. These mice were immunized twice with OVA and alum by intraperitoneal route (days 0 and 7) and challenged twice by intranasal route (days 14 and 21). Two days after the last challenge, the airway inflammation was evaluated by antibody levels, cellular migration, eosinophil peroxidase levels, cytokine and eotaxin production, and pulmonary mechanical parameters. Among the adoptively transferred primed lymphocytes, only CD4+ CD25+, CD8+ or the combination of both T cells impaired the production of total IgE and OVA-specific IgE and IgG1 antibodies, eosinophilic airway inflammation, Th2-type cytokines (IL-4, IL-5 and IL-13), eotaxin release and airway hyperreactivity. Moreover, airway recruited cells from CD4+ CD25+ and CD8+ T-cell recipient secreted more IL-10/TGF-â and IFN-ã, respectively. Moreover, we found that PAS-1 expands significantly the number of CD4+ CD25+ FoxP3+ and CD8+ ãäTCR+ cells. In conclusion, these findings demonstrate that the immunomodulatory effect of PAS-1 is mediated by these T-cell subsets.

PAS-1, a protein from Ascaris suum, modulates allergic inflammationvia IL-10 and IFN-c, but not IL-12

Helminths and their products have a profound immunomodulatory effect upon the inductive and effectorphases of inflammatory responses, including allergy. We have demonstrated that PAS-1, a protein isolatedfrom Ascaris suum worms, has an inhibitory effect on lung allergic inflammation due to its abilityto down-regulate eosinophilic inflammation, Th2 cytokine release and IgE antibody production. Here,we investigated the role of IL-12, IFN-c and IL-10 in the PAS-1-induced inhibitory mechanism using amurine model of asthma. Wild type C57BL/6, IL-12 / , IFN-c / and IL-10 / mice were immunized withPAS-1 and/or OVA and challenged with the same antigens intranasally. The suppressive effect of PAS-1was demonstrated on the cellular influx into airways, with reduction of eosinophil number and eosinophilperoxidase activity in OVA + PAS-1-immunized wild type mice. This effect well correlated with a significantreduction in the levels of IL-4, IL-5, IL-13 and eotaxin in BAL fluid. Levels of IgE and IgG1antibodies were also impaired in serum from these mice. The inhibitory activity of PAS-1 was alsoobserved in IL-12 / mice, but not in IFN-c / and IL-10 / animals. These data show that IFN-c andIL-10, but not IL-12, play an important role in the PAS-1 modulatory effect.

Early stages ofAscaris suuminduce airway inflammation andhyperreactivity in a mouse model

The inflammatory and functional changes that occur in murinelung after infection with 2500 infectiveAscaris suumeggswere studied in this work. A sequential influx of neutrophils,mononuclear cells and eosinophils occurred into airwaysconcomitantly with migration of larvae from liver to thelungs. Histological analysis of the lung showed a severe intraalveolarhaemorrhage at the peak of larval migration (day 8)and the most intense inflammatory cell infiltrate on day 14.AscarisL3 were found in alveolar spaces and inside bronchioleson day 8. The number of eosinophils was elevated inthe blood on days 8 and 14. The peak of eosinophil influx intothe lung was at day 14, as indicated by the high levels of eosinophilperoxidase activity, followed by their migration into theairways. The antibody response against egg and larval antigensconsisted mainly of IgG1 and IgM, and also of IgE andanaphylactic IgG1, that cross-reacted with adult worm antigens.Total IgE levels were substantially elevated during theinfection. Measurement of lung mechanical parametersshowed airway hyperreactivity in infected mice. In conclusion,the murine model ofA. suuminfection mimics the Th2-induced parameters observed in pigs and humans and can beused to analyse the immunoregulatory properties of thishelminth.

Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula.

OBJECTIVE: We examined the effect of standard formula and glutamine or glycine supplemented enteral formula on intestinal permeability and weight gain in children with malnutrition. METHODS: 80 children aged 2 to 60 months with a weight-for-age z-score less than -- 2 were studied. From December 1996 to April 1999, 27 study patients received nonsupplemented formula. From June 2001 to June 2002 an additional 53 patients were randomly assigned to receive formula supplemented with glutamine or glycine (isosmolar concentrations) for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed before and after 10 days of nutritional rehabilitation. Weight was measured before and after treatment. RESULTS: Patients were similar on admission with regard to age, sex, nutritional status and lactulose/mannitol ratio. The lactulose/mannitol ratio significantly improved (decreased) in children receiving formula supplemented with glutamine for 10 days but not in those receiving glycine or nonsupplemented formula. Weight gain occurred during therapy in all groups and was not statistically different among groups. CONCLUSION: Formula supplemented with glutamine improves intestinal barrier function compared with nonsupplemented formula but does not augment weight gain.

Protein adsorption on mixtures of hydroxyl- and methyl-terminated alkanethiols self-assembled monolayers.

The effect of surface composition and wettability on the adsorption of human serum albumin (HSA) was studied. Self-assembled monolayers (SAMs) containing mixtures of longer chain methyl- and shorter chain hydroxyl-terminated alkanethiols on gold were used to produce a range of surfaces with different wettabilities and exposed functional groups. Different SAMs were characterized by X-ray photoelectron spectroscopy, water contact angles, and Fourier transform infrared reflection absorption spectroscopy (IRAS). HSA adsorption onto the different SAMs was evaluated by contact angle measurements (wetting tension determinations), radiolabeling of proteins, and IRAS. Concerning HSA adsorption, all the techniques demonstrated higher HSA adsorption on more hydrophobic surfaces. The wetting tension measurements and IRAS suggested a gradual decrease of the HSA adsorption with increases of surface hydrophilicity. Radiolabeled albumin measurements also demonstrated a significant decrease of HSA adsorption on the pure hydroxyl-terminated SAMs. However, no significant differences were detected between mixed and pure methyl-terminated SAMs. Studies of HSA exchangeability with human fibrinogen have suggested that an ideal percentage of hydroxyl groups on the surface may increase albumin affinity without fibrinogen adsorption.

Albumin adsorption on cibacron blue F3G-A immobilized onto oligo(ethylene glycol)-terminated self-assembled monolayers.

Self-assembled monolayers can be tailored with specific ligands to a certain protein and at the same time prevent the non-specific adsorption of other proteins. Cibacron Blue F3G-A (CB-thiol) was successfully immobilized onto tetra(ethylene glycol)-terminated alkanethiol (CB-thiol). The affinity of human serum albumin (HSA) to immobilized Cibacron Blue F3G-A was studied using mixed thiolate self-assembled monolayers on gold with different n-alkyl chain lengths and functional terminal groups (CH(3)-; OH- and tetra(ethylene glycol)). Surfaces were characterized using X-ray photoelectron spectroscopy and water contact angle measurements. Albumin adsorption and exchangeability of the adsorbed albumin molecules with other albumin molecules in solution were evaluated using (125)I-radiolabeled HSA. Competitive adsorption between albumin and fibrinogen to the different self-assembled monolayers (SAMs) was also investigated. Results showed that the incorporation of CB-thiol on the monolayers does not increase the HSA adsorption and reversibility on the SAMs. However, although specific adsorption of HSA to the immobilized Cibacron Blue F3G-A was not demonstrated, the presence of CB-thiol decreases the affinity of fibrinogen to the OH-terminated SAMs.