bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of sources of resistance to damping-off (Rhizoctonia solani) in two phenological phases of watermelon
Authors: Cunha Fábio Sanchez da , Costa Antonio Elton da Silva , Capucho Alexandre Sandri , Dias Rita de Cássia Souza , Ishikawa Francine Hiromi
Published: June 2019

Sources of resistance to damping-off caused by Rhizoctonia solani were researched in watermelon accessions, in which thirty accessions were inoculated in two phenological phases (at seeding and seedling stages). The completely randomized design with five replications per accession was used in both phenological stages. The inoculation in seeding stage was carried out at the time of sowing, while for seedling the inoculation was done 15 days after sowing. In both stages the evaluation occurred 15 days after inoculation using a rating scale. At seeding stage, six accessions were moderately resistant to CMM-2967 of R. solani. However, no accession resistant to CMM-1053 and CMM-1052 isolates was recognized. Three accessions were resistant to CMM-1053 at the seedling stage. Posteriorly, inoculation was carried out using only accessions classified as resistant in the previous evaluations using both phenological stages. For CMM-1053, factorial scheme of 2x4 were used (two stages and four accessions). For assessments against isolate CMM-2967 a factorial scheme of 2x12 (two stages and 12 accessions) was used. We confirmed the results of first two experiments for both isolates. At seeding stage, all accessions were classified as susceptible to CMM-1053. However, at the seedling stage, only Crimson Swett was susceptible. For the CMM-2967, inoculated at the seeding stage, the accessions were classified into two groups (resistant and susceptible) (Scott-Knott at 5%). At seedling stage there was no statistical difference among eleven accessions and they were all classified as resistant. Due to difficulty of finding sources of resistance to damping off, the method of inoculation at seedling stage showed more efficient for this pathosystem and could facilitate the work of breeders and plant pathologists.
Leadership and social responsibility from the perspective of gender
Authors: Manuel Andrade Navia Juan , Ramírez Plazas Elías , Catherine Diaz Yenny
Published: June 2019

This study established the relationship between transformational leadership and social responsibility practices in women’s organizations that produce special coffees in southern Colombia. To measure these variables using Likert scales, two questionnaires were applied: the Multifactor Leadership Questionnaire 5X short version (MLQ-5X) to measure transformational leadership, and a tool developed by the researchers to measure social responsibility. Cronbach’s Alpha (α) values for the two variables showed excellent consistency (α = 0.95 and 0.90 for transformational leadership and social responsibility, respectively). For the analysis of the information, the structural equation model was used to validate the hypothesis using the SPSS AMOS software. The results indicate a significant and positive correlation between the transformational leadership practices and the perception of social responsibility, especially in the dimensions of idealized influence (behavior and attributed) and intellectual stimulation of transformational leadership, and in the dimensions of labor issues and social responsibility. These findings are consistent with existing literature, and complement aspects not addressed before (e.g. correlation between transformational leadership and social responsibility practices in women’s organizations) in the framework of gender in non-conventional organizations.
Imparcialidad y particularismo moral
Authors: Alegría Fuentes Daniela
Published: June 2019

Este artículo busca mostrar que el particularismo moral es una alternativa viable a las éticas dominantes desde la modernidad hasta nuestros días (i.e., ética kantiana y utilitarista); teorías que durante las últimas décadas han sido criticadas, especialmente, por la exigencia del requisito de imparcialidad moral. El agente en estas éticas delibera imparcialmente debido al universalismo de sus principios morales. Sugeriré que el particularismo moral, en tanto excluye la imparcialidad como un factor relevante en las deliberaciones de los agentes, presenta razones para ser una ética plausible.
Exploring Young People’s Perceptions of the Effectiveness of Text-Based Online Counseling: Mixed Methods Pilot Study
Authors: Navarro Pablo , Bambling Matthew , Sheffield Jeanie , Edirippulige Sisira
Published: June 2019

Background

Young people aged 10-24 years are at the highest risk for mental health problems and are the least likely to seek professional treatment. Owing to this population’s high consumption of internet content, electronic mental (e-mental) health services have increased globally, with an aim to address barriers to treatment. Many of these services use text-based online counseling (TBOC), which shows promising results in supporting young people but also greater variance in outcomes compared with adult comparators.

Objective

This pilot study qualitatively explored the characteristics of users aged 15-25 years accessing TBOC services, their motivations for access, and their perceptions about factors believed to influence the effectiveness of these modalities.

Methods

E-surveys were administered naturalistically to 100 young service users aged 15-25 years who accessed webchat and email counseling services via an Australian e-mental health service. Thematic analysis of qualitative themes and quantitative descriptive and proportional data presented in electronic surveys were examined across the areas of user characteristics, motivations for selecting TBOC modalities, and their perceptions of TBOC effectiveness.

Results

Participants were predominately female high school students of Caucasian or European descent from middle socioeconomic status, living with their parents in major cities. Four domains and various themes and subthemes were related to participants’ reasons for accessing TBOC and perceptions of its effectiveness: user characteristics (ie, physical and mental health syndrome and perceived social difficulties), selection factors (ie, safety, avoidance motivation, accessibility, and expectation), factors perceived to increase effectiveness (ie, general therapeutic benefits, positive modality and service factors, and persisting with counseling to increase benefit), and factors perceived to decrease effectiveness (ie, negative modality and service factors, and persisting with counseling despite benefit).

Conclusions

Participants were motivated to use TBOC to increase their sense of safety in response to negative perceptions of their social skills and the response of the online counsellor to their presenting problem. By using TBOC services, they also sought to improve their access to mental health services that better met their expectations. Factors that increased effectiveness of TBOC were the counsellor’s interpersonal skills, use of text-based communication, and persisting with beneficial counseling sessions. Factors that reduced TBOC effectiveness were poor timeliness in response to service requests, experiencing no change in their presenting problem, not knowing what postcounseling action to take, and persisting with ineffective counseling sessions.
FORMULATION AND EVALUATION OF LIQUISOLID COMPACTS OF LORNOXICAM
Authors: Mokashi Asma Azaruddin , GAIKWAD SNEHALATA L.
Published: June 2019

Objective: Objective of the present investigation was to enhance the solubility and dissolution rate of poorly water-soluble drug lornoxicam using liquisolid technique with comparative determination of in vitro release profile of liquisolid compacts and conventional formulation of lornoxicam.

Methods: Formulation was prepared by a liquisolid technique using different drug concentration in a liquid vehicle and different carrier/coating ratio. Prepared liquisolid compact was evaluated for Fourier transform infrared (FTIR) spectra analysis, differential scanning calorimetry (DSC), X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and in vitro dissolution study.

Results: The result showed that liquisolid compacts of lornoxicam displayed significantly higher drug release rate as compared to pure drug and conventional tablet prepared. The results of both DSC and X-ray crystallography indicated loss of crystallinity of the drug upon formulated into the liquisolid compact.

Conclusion: Dissolution rate of the drug from liquisolid compacts was affected by changing the drug concentration and excipient ratio. The liquisolid technique appeared to be a promising approach for improving the dissolution of poorly soluble drug lornoxicam.
NOVEL HPTLC-DENSITOMETRIC METHOD FOR THE ESTIMATION OF TERIFLUNOMIDE IN TABLET DOSAGE FORM
Authors: Vishwas T. S. , Gurupadayya B. M. , Jain Rupshee
Published: June 2019

Objective: The current work is intended towards the development of a novel, simple and precise high-performance thin layer chromatographic (HPTLC) method coupled with a densitometer for the estimation of teriflunomide (TEF) present in the marketed formulation.
Methods: The chromatographic development was performed on aluminum plates coated with silica gel 60 F254 using toluene: ethyl acetate: glacial acetic acid (7.5:2: 0.5 v/v/v) as the mobile phase. Densitometric scanning was achieved at the absorbance maxima, UV 284 nm.
Results: Well separated band was observed with Rf value 0.46. The calibration curve plotted in the concentration range 100-700ng/band exhibited an excellent linear relationship with the r2 value of 0.9928. The method was found to comply with all the validation parameters as per the ICH guidelines.
Conclusion: The method ensures minimal use of mobile phase with minimal run time compared to other reported analytical methods. This validated method can be used by quality control laboratories for the routine quantitative analysis of tablets consisting of Teriflunomide.
Viviendo con el mar: inestabilidad litoral y territorios en movimiento en La Barra, Pacífico colombiano
Authors: Galindo Orrego María Isabel
Published: June 2019

En las playas de La Barra, a orillas del océano Pacífico colombiano, la vida acontece amarrada al movimiento del mar. La inquietud acerca de cómo se perfilan formas de habitar en medio del cambio permanente suscitado por el empuje del agua y cómo tal inestabilidad es asimilada por quienes la experimentan son las preguntas que

inspiran esta indagación. El artículo rastrea etnográficamente la formación de La Barra al compás de las mutaciones del entorno y explora las explicaciones que los saberes locales otorgan a dicha alteración. Desde una mirada antropológica que dialoga con la historia ambiental, este trabajo piensa la agencia humana en relación con las agitaciones de la naturaleza mediante una trama telúrica que liga la humanidad a las transformaciones de la tierra.
Apontamentos sobre a experiência inclusiva
Authors: Queiroz Igor Henrique Lopes de
Published: June 2019

O presente trabalho apresenta algumas considerações sobre o estágio curricular supervisionado em História no Colégio de Aplicação da Universidade Federal de Santa Catarina (UFSC), levantando questões sobre a experiência de trabalhar com crianças de inclusão em sala de aula.
Ensinando História: distâncias entre teorias e práticas
Authors: Queiroz Igor Henrique Lopes de
Published: June 2019

O presente trabalho relata a experiência de estágio supervisionado em História (UDESC) em uma quarta série (quinto ano) da E.E.B. Simão Hess, em Florianópolis. Percebemos, em observação, que o material utilizado em sala para o ensino da disciplina reproduzia preconceitos a respeito de indígenas, africanas/os e afrodescendentes sob a condição de escravidão no período colonial brasileiro. Utilizando referenciais teóricos da Didática da História, investigamos as ideias das crianças sobre a temática e, a partir de textos, imagens e brincadeiras, estimulamos as crianças a construírem outras histórias e representações sobre o tema.
A experiência no ensino de história voltado ao vestibular: um diálogo em torno da construção do conhecimento em um projeto de extensão na cidade do Rio Grande-RS
Authors: Cipriano Diego Mendes , Machado Carlos Roberto Da Silva
Published: June 2019

O objetivo do trabalho é discutir, na perspectiva de dois educadores, em que medida foi possível, num projeto de ensino/extensão que privilegia a “memorização de conteúdos”, a construção de um conhecimento histórico para a vida em sociedade, nas atividades do curso preparatório ao vestibular “Grupo de Estudos Paidéia”, da Universidade Federal do Rio Grande – FURG. Para tanto, relatamos os antecedentes desta proposta de ensino e o aprimoramento de seus pressupostos didático-pedagógicos, situando a visão de História que procuramos imprimir em nossas atividades educativas. Também, discutimos os aspectos fundamentais dos resultados expressos em diagnóstico que realizamos junto aos educandos, com o fim de verificar as concepções dos mesmos sobre o processo de ensino-aprendizagem e a idéia de história que expressaram na sondagem, tendo em vista verificar as implicações destas percepções frente à metodologia que propusemos.
Educação e saúde no contexto escolar: uma experiência de abordagem lúdica com o tema saúde cardiovascular nos anos iniciais
Authors: Lara Simone , Fernandes Salgueiro Andréia Caroline , Copetti Jaqueline , Goulart Lanes Karoline , Puntel Robson Luiz , Folmer Vanderlei
Published: June 2019

Devido à relevância da inserção do tema saúde cardiovascular no contexto escolar dos anos iniciais, o presente estudo objetivou apresentar uma proposta de abordagem deste tema através da aplicação de ferramentas lúdicas aos anos iniciais, por estagiários do curso normal, e posteriormente, verificar a percepção de ambos sobre a relevância desta proposta. Por fim, o conhecimento mais pertinente sobre o tema saúde cardiovascular pelos estagiários do curso normal, bem como fatores associados à promoção da saúde do escolar nos anos iniciais, foram algumas das contribuições deste estudo para melhorar o processo de ensino aprendizagem no ensino de ciências e saúde.
Conhecendo-SE para conservar-SE: prática educativa interdisciplinar entre Ciências e Redação
Authors: Donato Christiane Ramos
Published: June 2019

O projeto foi posto em prática no ano de 2009, em uma escola da rede particular de ensino em Aracaju, Sergipe, com seis turmas dos sétimos anos. Teve como objetivo geral despertar nos estudantes a importância da conservação da cultura e, também, do conhecimento sadio da interação pessoal de cada um com: seu próprio corpo, seus colegas e o meio ambiente do Estado de Sergipe. Para atingir esse objetivo, o trabalho foi dividido em três etapas: levantamento bibliográfico e coleta de dados sobre os temas abordados; disponibilização das informações coletadas à disposição dos alunos durante as aulas das disciplinas de Ciências e Redação; verificação do aprendizado e sensibilização dos estudantes a partir do resgate do tema, mas desta vez com criações próprias deles. Observou-se que o andamento das atividades organizadas por um tema transversal facilitou o aprendizado através da motivação, melhorando a participação nas aulas e, consequentemente, o rendimento escolar.
Docência em Teatro e transdisciplinaridade: a experiência do Projeto Amora do Colégio de Aplicação da UFRGS
Authors: Rodrigues Lisinei Fatima Dieguez
Published: June 2019

O trabalho propõe-se a analisar o ensino de Teatro desenvolvido no contexto da Educação Básica numa perspectiva de abordagem transdisciplinar para o conhecimento na experiência do Projeto Amora do CAP/UFRGS. Ao oferecer um processo contínuo de estruturação de esquemas que possibilita aos estudantes realizar operações cognitivas de identificação (o que é só do Teatro), de comparação (o que não é só do Teatro) e de relação (o que é do Teatro e de outras disciplinas), as ações pedagógicas no Projeto Amora permitem que se formulem generalizações acerca do ato teatral. Através da análise dos resultados da pesquisa desenvolvida na Dissertação de Mestrado, defendida junto ao Programa de Pós-Graduação em Artes Cênicas e que gerou este artigo, foi possível consolidar a ideia de que as especificidades do campo de conhecimento podem destacar-se na abordagem transdisciplinar.
O uso do computador como estratégia para discutir em sala de aula o tabagismo na adolescência
Authors: De Jesus Baptista Gomes Luciana Maria
Published: June 2019

Este artigo descreve um relato de experiência desenvolvido em uma escola da área suburbana da cidade do Rio de Janeiro, com duas turmas de 9º ano do Ensino Fundamental. Reconhecendo a necessidade de discutir o tabagismo na adolescência, haja visto que este público é considerado “reserva de reabastecimento” pelas indústrias do tabaco ao mesmo tempo que o tabagismo é a principal causa de morte evitável pela Organização Mundial de Saúde (OMS), a estratégia foi a de utilizar o computador como uma ferramenta didática, em que os alunos puderam utilizá-los em diferentes momentos. Foi aplicado inicialmente um questionário para diagnose das turmas e os resultados das atividades foram analisados à luz de Vygotsky. Apesar de o tabagismo ser um tema conhecido pelos alunos, o uso do computador foi motivador para que eles se sentissem estimulados a participar, levando a um engajamento cada vez maior a cada etapa do projeto.
Análise da saúde docente em uma escola municipal de Porto Alegre
Authors: Mendes Aline Rocha
Published: June 2019

O presente trabalho apresenta parte dos resultados encontrados em uma pesquisa, realizada no PPGEdu-PUCRS, de cunho quantitativo, que objetivou detectar e analisar as condições de mal-estar e bem-estar de 30 professores de uma escola do Ensino Fundamental da Rede Municipal de Ensino de Porto Alegre-BR, por meio de informações sobre suas licenças para tratamento de saúde (LTS) e verificou-se que 35,4% dos professores solicitaram esta concessão, respostas a um questionário de avaliação do Bem/Mal-estar Docente, analisadas com Estatística Descritiva e Inferencial. Na análise das variáveis do questionário, inferiu-se que estes educadores parecem querer continuar na profissão docente, com metas e expectativas elevadas para si e para seus educandos, embora tenham apresentado índices elevados de estresse e exaustão. Os resultados da investigação foram divulgados na escola pesquisada, dando-se assim um retorno aos docentes.
Respeito em todo o tempo: um projeto transdisciplinar desenvolvido com estudantes dos quartos anos de uma escola de tempo integral
Authors: Silveira Hermínia Maria Martins Lima , Amânco Roselene Alves
Published: June 2019

Este trabalho versa sobre a trajetória de um projeto transdisciplinar intitulado “Respeito em todo o tempo” desenvolvido nas turmas iniciais do Segundo Ciclo de Formação Humana de uma escola de tempo integral. Busca-se aqui relatar e descrever algumas das atividades do projeto e apresentar reflexões sobre as possíveis implicações desse tipo de trabalho para a vida dos estudantes envolvidos. O objetivo do projeto foi convidar as crianças a refletirem sobre o respeito como essencial para fortalecer o convívio e a cooperação no espaço escolar, na tentativa de que eles possam se responsabilizar pelos seus atos, entendendo que, embora indivíduos, são parte importante da sociedade.
Filosofar para comunicar: espaço dos surdos na educação de jovens e adultos (EJA)
Authors: Caldas Ana Luiza Paganelli
Published: June 2019

Resumo: Este trabalho é uma sumária reflexão sobre aplicar a filosofia na educação como ferramenta para construir o pensamento. O filosofar no sentido de construir significado de mundo, de construir subjetividade, de construir a identidade surda a partir da educação pressupondo que muitos surdos nascem em famílias ouvintes e são educados em escolas de ouvintes e, às vezes, também chegam a idade adulta sem acesso a educação escolar. Meu princípio é minha realidade enquanto surda e educadora. Procuro assim reforçar o ideal de que a Língua Brasileira de Sinais – Libras, é a língua dos surdos e é ela que permeia os processos educativos desta comunidade, sejam crianças, jovens ou adultos. Portanto, as escolas bilíngues para surdos são de fundamental importância para que o sujeito surdo participe da construção de sua autonomia para atuar numa sociedade ouvinte e que exige preparação para o mercado de trabalho.
E quando o ‘lugar’ é a metrópole? Pesquisa e ensino de Geografia no contexto metropolitano de Porto Alegre
Authors: Fernandes Ana Clara
Published: June 2019

A necessidade de relacionar os estudos de Geografia daEducação Básica com o cotidiano dos alunos é tema discutidopor vários autores já há algumas décadas. Ao problematizar sobreos estudos geográficos na França dos anos 1970 do século XX,Lacoste (1988) argumenta em A Geografia – Isso serve, em primeirolugar, para fazer a guerra sobre a importância de atividades pedagógicasnas aulas de Geografia que possibilitem aprender a ler oespaço vivido (a carta) como contraposição à postura ideológicade negar esse conhecimento aos cidadãos em prol dos interessesdas classes dominantes.
O perfil dos alunos dos Ensinos Fundamental e Médio do Colégio de Aplicação da UFRGS
Authors: Nodari Karen Elisabete Rosa
Published: June 2019

Conhecer o perfil dos alunos do Ensino Fundamental eMédio do Colégio de Aplicação da UFRGS
As cidades são meios e os meios são as mensagens: uma leitura estético-política das reformas urbanas na América Ibérica durante a Belle Époque
Authors: Arraes Marcos Alexandre , Falcão Matheus
Published: June 2019

O presente artigo se propõe a demonstrar como a modernidade fez emergir, junto com o desejo de renovação urbana, uma lógica tecnopolítica hegemônica, condensada em princípios estéticos de caráter socialmente excludente. A narrativa se dá a partir de uma contextualização histórica das transformações urbanas no início da modernidade na Ibero-América e pontua a presença de um projeto tecnopolítico norteador dos princípios estéticos ali presentes. A narrativa foi construída a partir de apresentação de dados e provocações de ordem analítica, sem, contudo, deter-se em análises conceituais profundas.
Duas histórias processuais memória e tortura na Operação Barriga Verde 1975
Authors: Torres Mateus Gamba
Published: June 2019

O presente artigo visa a trabalhar com alguns dos elementos que davam sustentação ao regime militar que, em meados da década de 1970, apenas começava a sentir os primeiros movimentos de crise que levariam à solução conciliatória da Nova República, na década seguinte. Compreende-se aqui que as decisões do judiciário militar e, particularmente, o processo judicial que se formou contra os acusados de reorganização do Partido Comunista em Santa Catarina como fruto da Operação Barriga Verde, extrapolavam o âmbito meramente do formalismo jurídico, envolvendo todo um imaginário construído ao longo de várias décadas e que se consubstanciava nos argumentos e sentenças proferidas. Nesse processo chamam a nossa atenção dois casos que demonstram as torturas e ilegalidades visíveis em documentos produzidos pelo próprio judiciário.
O combate de Rio das Antas (novembro de 1914): algumas considerações iniciais
Authors: Espig Márcia Janete
Published: June 2019

A colônia de Rio das Antas foi fundada pela Brazil Development & Colonization Company (empresa de Colonização ligada à Brazil Railway Company) em terras das quais os moradores tradicionais haviam sido expulsos, tendo sido ocupada por imigrantes alemães e poloneses. Em 2 de novembro de 1914, no contexto da Guerra do Contestado, essa vila foi atacada pelo comandante geral dos rebeldes, Francisco Alonso, à frente de um piquete caboclo. Esse episódio, conhecido como combate de Rio das Antas, ficou marcado pela resistência dos colonos, pela morte de Alonso e pela fuga dos imigrantes da região. Neste artigo, pretendo discutir a fraca atenção dedicada a essa temática pela historiografia, trazendo algumas hipóteses de análise.
Effects of processing methods and levels of inclusion of Jatropha curcas kernel meal on performance, organ characteristics, haematology and serum chemistry of finisher broiler chickens
Authors: Ojediranemiola Taiwo , Ajayi Ayodeji , Isiak A.
Published: June 2019

Three hundred 21-day-old broiler chicks were reared using a 3 x 3 factorial
model in a completely randomized design with 10 treatment groups having 3
replicates of 10 birds each. The birds were raised on a commercial starter
diet at the starter phase before being allotted into dietary groups in a
21-d feeding trial at the finisher phase. The interaction between treatment
and varying inclusion levels of processed-fermented Jatropha curcas (L)
kernel meals (JKM) on the performance of broiler chicks was investigated.
Jatropha curcas kernels were subjected to three different processing
methods, namely: raw defatted fermented meal (RDFM), cooked defatted
fermented meal (CDFM) and lye treated defatted fermented meal (LDFM). Each
meal was included at varying inclusion levels of 2.5%, 5.0% and 7.5% such
that diet 1 (control) contained 0% JKM while diets 2, 3, 4 contained 2.5%,
5.0% and 7.5% RDFM, diets 5, 6, and 7 contained 2.5%, 5.0% and 7.5% CDFM and
diets 8, 9, 10 contained 2.5%, 5.0% and 7.5% LDFM. Feeding differently
processed-fermented JKM to these broilers did not (p>0.05) compromise the
feed conversion ratio. The results indicated an improvement (p<0.05) in the
weight gain of broiler chicks fed CDFM and LDFM at 2.5 and 5.0% inclusion
levels respectively. There were significantly (P<0.05) elevated levels of
alkaline phosphatase and creatinine in their blood serum. The kidney, lungs
and proventriculus of birds fed CDFM showed significant differences (p<0.05)
among the treatments. Therefore, finisher broilers could tolerate up to 5.0%
inclusion level of LDFM.
100-OR: Defective Mitochondrial Gene Expression in Brown Adipocytes Suppresses Food Intake by Batkine GDF15
Authors: WANG BIAO
Published: June 2019

Adaptive thermogenesis fueled by mitochondrial respiration in brown adipose tissue (BAT) contributes to thermoregulation and energy expenditure. However, whether BAT can regulate energy balance beyond thermogenesis remains unknown. Here, we describe that the Leucine-rich PPR motif-containing protein (Lrpprc) specifically regulated mtDNA-encoded gene expression in brown adipocytes. Brown adipocyte-specific Lrpprc knockout mice (LrpprcBKO) exhibited electron transport chain proteome imbalance and defective β-adrenergic-stimulated adaptive thermogenesis at room temperature and thermoneutrality. Paradoxically, LrpprcBKO mice were lean at normal chow and were protected against high-fat-diet (HFD)-induced metabolic abnormalities at both ambient temperatures. Lrpprc-deficient brown adipocytes exhibited enhanced Atf4-mediated integrated stress response and GDF15 secretion. Blocking GDF15 partially reversed the food intake and adiposity phenotypes in HFD-fed LrpprcBKO mice at thermoneutrality. Collectively, our results reveal that specific reduction of mtDNA gene expression in brown adipocytes induces a trade-off between BAT thermogenic capacity and systemic metabolism, which is in part through a GDF15-mediated BAT-to-brain crosstalk. These new findings may provide new therapeutic strategies for combating metabolic disorders.

Disclosure

B. Wang: None.

Funding

National Institutes of Health; Larry L. Hillblom Foundation
1016-P: A Novel GLP-1 and FGF-21 Dual Agonist Drug Protects Mice from Obesity and Hyperglycemia
Authors: GILROY CASLIN A. , CAPOZZI MEGAN , SU JONATHAN C. , TONG JENNY , D’ALESSIO DAVID A. , CAMPBELL JONATHAN , CHILKOTI ASHUTOSH
Published: June 2019

As the incidence of diabetes increases, the development of new therapeutic strategies is essential. Recent evidence supports combination therapies that incorporate complementary mechanisms of action as potent and effective. We have developed a unimolecular dual agonist by combining the incretin glucagon-like peptide-1 (GLP-1) and the metabolic regulatory factor fibroblast growth factor 21 (FGF-21). We hypothesized that this agent would merge the insulinotropic and anorectic effects of GLP-1 with enhanced insulin sensitivity and energy expenditure due to FGF-21 signaling. The dual agonist is a single polypeptide fusion, with GLP-1 located at the N-terminus and FGF-21 at the C-terminus. This orientation allows each peptide to activate its receptor, while the linear architecture enables facile synthesis in a bacterial expression system. Fused between GLP-1 and FGF-21 is an elastin-like polypeptide (ELP) that serves as both a flexible linker and a circulation-enhancing scaffold. The ELP used herein is designed such that it undergoes a thermally initiated phase transition triggered by body heat upon subcutaneous (s.c.) injection, resulting in a slow-dissolving drug depot. A single s.c. injection of GLP-1-ELP-FGF-21 into diabetic db/db mice significantly reduced ambient blood glucose levels from above 300 mg/dL to sustained levels below 150 mg/dL for 8 days. Db/db mice treated once-weekly for 4 weeks had mean body weights that were 24% and 16% lower than mice treated weekly with vehicle or long-acting GLP-1, respectively. Dual agonist treatment also conferred greater reductions in % HbA1c and circulating lipids. These results demonstrate the efficacy of a novel unimolecular drug to correct multiple metabolic abnormalities in a diabetic mouse model. Moreover, the improved outcomes compared to a GLP-1-based drug support the dual agonist mechanism. Incorporation of an ELP allows advantageous temporal control of drug delivery, thus making the GLP-1/FGF-21 dual agonist a promising new diabetes treatment.

Disclosure

C.A. Gilroy: Employee; Spouse/Partner; Becton, Dickinson and Company. M. Capozzi: None. J.C. Su: None. J. Tong: None. D.A. D'Alessio: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company, Merck & Co., Inc. J. Campbell: Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. A. Chilkoti: Advisory Panel; Self; PhaseBio Pharmaceuticals, Inc.

Funding

National Institutes of Health
1017-P: Continuous Glucose Monitoring Reveals Comprehensive Glucose Control with MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity
Authors: PARKER VICTORIA E.R. , ROBERTSON DARREN , WANG TAO , HORNIGOLD DAVID C. , POSCH MAXIMILIAN G. , HEISE TIM , PLUM-MOERSCHEL LEONA , MEIER JURIS J. , SCHLICHTHAAR HEIKE , KLAUS BEATE M. , AMBERY PHILIP , HIRSHBERG BOAZ
Published: June 2019

Background: MEDI0382 is an oxyntomodulin-like peptide with GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). Continuous glucose monitoring (CGM) is valuable for evaluating glucose-lowering efficacy.

Methods: As an exploratory part of a double-blind phase 2a study, CGM was performed for 52 days with a Freestyle Libre. Patients with T2DM received daily SC MEDI0382 (n = 26) or placebo (n = 13) for 49 days; doses were up-titrated weekly from 50 to 300 µg. CGM assessed percent time spent in target range (70-140 mg/dL) and hypoglycemia (<54 mg/dL), as well as 7-day mean 24-h glucose and CV.

Results: Over 52 days, 95% patients had >70% complete CGM data. Time spent in target range was significantly greater with MEDI0382 vs. placebo (64.8-78.0% vs. 42.5-53.0%; min-max; all P ≤ 0.05). Time spent at <54 mg/dL was <1% at all MEDI0382 doses and was not significantly different vs. placebo. A significant reduction in mean glucose with MEDI0382 (118.8-133.2 mg/dL) vs. placebo (153-154.8 mg/dL; all P ≤ 0.033) was observed, and CV was lower with MEDI0382 (0.19-0.21) vs. placebo (0.25-0.26; all P ≤ 0.030).

Discussion: MEDI0382 rapidly stabilized glucose levels, improved glycemic variability, and delivered a consistent decrease in mean glucose. The benefits of more time spent in target range will need to be confirmed in larger trials.

Disclosure

V.E.R. Parker: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca. D. Robertson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; Self; AstraZeneca. T. Wang: Employee; Self; MedImmune. D.C. Hornigold: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.G. Posch: None. T. Heise: Advisory Panel; Self; Mylan. Research Support; Self; ADOCIA, Boehringer Ingelheim International GmbH, Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, MedImmune, Mylan, Nordic Bioscience, Novo Nordisk A/S, Pfizer Inc., Poxel, Saniona, Sanofi, Wockhardt, Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. L. Plum-Moerschel: None. J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. H. Schlichthaar: None. B.M. Klaus: None. P. Ambery: Employee; Self; AstraZeneca. B. Hirshberg: Employee; Self; AstraZeneca.

Funding

AstraZeneca
1032-P: Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed-Ratio Combination vs. Insulin Glargine in Japanese Patients with T2DM
Authors: KANETO HIDEAKI , TAKAMI AKANE , SPRANGER ROBERT , AMANO ATSUSHI , WATANABE DAISUKE , NIEMOELLER ELISABETH
Published: June 2019

The fixed ratio combination of insulin glargine/lixisenatide (iGlarLixi) has been shown in a Western population to improve glycemic control in a convenient single daily injection. This open-label trial assessed the efficacy and safety of 26-week treatment of iGlarLixi and insulin glargine (iGlar) in Japanese patients with T2DM inadequately controlled on basal insulin and oral antidiabetic drugs. After a 12-week run-in with metformin and iGlar, patients were randomized to iGlarLixi (n=255) or iGlar (n=257). Starting from a mean baseline (BL) HbA1c of 8.25%, the decrease in the iGlarLixi group was significantly greater than in the iGlar group (LS mean difference [SE]: -0.74% [0.063], p<0.0001) (Figure). Significantly more patients reached the HbA1c target of <7% at Week 26 with iGlarLixi than with iGlar (51.8% vs. 16.0%, p<0.0001). Change in body weight from BL to Week 26 was -0.51 kg with iGlarLixi and +0.55 kg with iGlar (p<0.0001). Both treatments were well tolerated. Documented symptomatic hypoglycemia (≤70 mg/dL) was similar in the two treatment groups (iGlarLixi: 18.8%, iGlar: 16.7%). Nausea was reported in 16.9% (iGlarLixi) and 0.8% (iGlar).

In conclusion, iGlarLixi showed superior glycemic control to iGlar, with a beneficial effect on body weight, no additional risk of hypoglycemia, and lower rate of nausea than reported with lixisenatide.

Disclosure

H. Kaneto: Research Support; Self; Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co ., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co ., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. A. Takami: Employee; Self; Sanofi K.K. R. Spranger: Employee; Self; Sanofi-Aventis Deutschland GmbH. A. Amano: Employee; Self; Sanofi K.K. D. Watanabe: Employee; Self; Sanofi K.K. E. Niemoeller: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi.

Funding

Sanofi K.K.
1035-P: VN-B101 in Combination with Metformin/Sitagliptin or Metformin/Ertugliflozin Synergistically Improves Glycemic Control in db/db Mice
Authors: WANG PEI-RAN , CHEN HUI-LING
Published: June 2019

Type 2 diabetes mellitus is a common chronic and progressive disease arising from a complex pathophysiology, a single pharmacological agent can only address limited pathophysiologic targets and does not provide adequate glycemic control, leading to an increasingly interest in the development of combination therapies in order to achieve the goal. Though VN-B101, the VitNovo’s leading diabetes drug candidate, has demonstrated its dual combination treatment with metformin is safe and efficacious in patients with type 2 diabetes, VN-B101 triple combination treatment has yet to be studied that may create more treatment options for diabetes patients. The major objective of the present studies was to evaluate the efficacy of VN-B101 triple combination treatment with (1) metformin/sitagliptin (DPP-4i) or (2) metformin/ertugliflozin (SGLT2i) in db/db mice. Oral glucose tolerance test (OGTT) was performed after 4 weeks of combination treatment (VN-B101: 240mg/kg/day; metformin: 150mg/kg/day; sitagliptin: 40mg/kg/day; ertugliflozin: 10mg/kg/day). The % reduction of incremental glucose AUC during OGTT in each group was calculated to evaluate the treatment effects on glycemic control. The results show (1) VN-B101 in combination with metformin/sitagliptin synergistically improves glycemic control (VN-B101 + metformin/sitagliptin: -136.9% vs. VN-B101: -26.1% and metformin/sitagliptin: -55.6%); (2) VN-B101 in combination with metformin/ertugliflozin synergistically improves glycemic control (VN-B101 + metformin/ertugliflozin: -140.1% vs. VN-B101: -26.1% and metformin/ertugliflozin: -61.5%). These exciting results open new therapeutic possibilities in the treatment of type 2 diabetes mellitus. Clinical trial of either triple combination treatments are currently conducted in Australia.

Disclosure

P. Wang: None. H. Chen: None.
1047-P: Can Closed-Loop Overcome High Day-to-Day Variability of Insulin Needs in Inpatients on General Wards?
Authors: BOUGHTON CHARLOTTE K. , BALLY LIA , THABIT HOOD , HARTNELL SARA , HERZIG DAVID , VOGT ANDREAS , ANDEREGGEN EVELINE , RUAN YUE , WILINSKA MALGORZATA E. , EVANS MARK , WERTLI MARIA M. , COLL ANTHONY P. , STETTLER CHRISTOPH , HOVORKA ROMAN
Published: June 2019

Aim: To assess the ability of fully closed-loop insulin delivery to accommodate day-to-day variability in insulin requirements in noncritical care setting.

Methods: We retrospectively analyzed insulin delivery during closed-loop studies in inpatients with hyperglycaemia requiring insulin on general wards (type 1 diabetes excluded). Coefficient of variation (CV) quantified day-to-day variability of insulin requirements over 5 to 15 days of closed-loop use. Participants were stratified into tertiles according to variability of insulin requirements.

Results: Data from 487 days (55 participants) were analyzed. Participants with higher CV of insulin requirements had comparable mean glucose (149 vs. 153mg/dL; P=0.59; Table) and time in target glucose 100-180mg/dL (67.8 vs. 67.9%; P=0.99) to those with lower CV. There was no increase in hypoglycemia in those with higher CV (P=0.67). Those with higher CV were younger than those with lower CV (66 vs. 72years; P=0.037). Weight, gender, HbA1c, diabetes/insulin duration, use of steroids/dialysis/nutrition support were comparable (ns).

Conclusions: Fully closed-loop insulin delivery can accommodate highly variable insulin requirements without compromising glucose control or increasing the risk of hypoglycaemia in inpatients receiving insulin therapy on general wards.

Disclosure

C.K. Boughton: None. L. Bally: None. H. Thabit: Research Support; Self; Dexcom, Inc. S. Hartnell: Advisory Panel; Self; Dexcom, Inc., JDRF. Speaker's Bureau; Self; Sanofi. D. Herzig: None. A. Vogt: None. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Dexcom, Inc., Medtronic, Roche Diabetes Care, Zucara Therapeutics Inc. Research Support; Self; MedImmune, Sanofi. Speaker's Bureau; Self; AstraZeneca. Other Relationship; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Abbott, Dexcom, Inc., Medtronic. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; B. Braun Medical Inc., Medtronic.
105-OR: Lineage Determination of Endocrine Progenitors in Murine and Human Pancreatic Development
Authors: WONG DANIEL M. , BYRNES LAUREN , BOUZA JACQUELYN O. , PEIXOTO GABRIEL , MCMULLEN REED , SNEDDON JULIE B.
Published: June 2019

Generation of functional beta cells for regenerative medicine would benefit from an increased understanding of pancreatic endocrine cell differentiation. During pancreatic development, expression of Ngn3 defines the progenitor cells that will differentiate into one of five endocrine lineages, including the beta cell. Here, we identify and further characterize a distinct endocrine progenitor population defined by differential expression of a transcription factor named Fev in murine and human endocrine cell development. Using single-cell RNA-sequencing and genetic lineage tracing, we build a transcriptomic profile of murine Fev+ progenitors that is distinct from that of Ngn3+ progenitors and reconstruct lineage relationships among Ngn3+, Fev+, and differentiated, hormone+ cells. We further identify candidate transcriptional regulators along the differentiation trajectory of this Fev+ progenitor population toward the alpha or beta cell lineages. Translating our findings in murine pancreatic development to that of human, we identify an analogous FEV+ population and putative gene regulators of endocrine cell fate in human fetal pancreas. In a stepwise differentiation platform designed to generate beta cells from human embryonic stem cells (hESCs), we also uncover robust FEV expression in endocrine progenitors prior to their differentiation into insulin-producing beta cells. Single-cell RNA-sequencing and lineage reconstruction of hESC-derived cells at the differentiated beta cell stage reveal FEV+ cells that may represent endocrine progenitors that have failed to acquire a beta cell identity; this failure of FEV+ endocrine cell differentiation may facilitate in uncovering the required molecular signals and genetic circuitry that push endocrine progenitors toward a beta cell fate. This work establishes a new model of pancreatic endocrine cell differentiation and identifies a Fev+ endocrine progenitor as a new cell stage in endocrine lineage determination.

Disclosure

D.M. Wong: None. L. Byrnes: None. J.O. Bouza: None. G. Peixoto: None. R. McMullen: None. J.B. Sneddon: Advisory Panel; Spouse/Partner; Akouos. Advisory Panel; Self; Encellin. Advisory Panel; Spouse/Partner; Encellin. Consultant; Self; Semma Therapeutics, Inc.

Funding

Nora Eccles Treadwell Foundation; University of California, San Francisco
1054-P: Insulin Sensitivity from Sensor and Pump Data in Youths with Type 1 Diabetes: Hybrid Closed-Loop Validation
Authors: SCHIAVON MICHELE , GALDERISI ALFONSO , KRAEMER KRISTEN A. , COBELLI CLAUDIO , MAN CHIARA DALLA , CENGIZ EDA
Published: June 2019

Estimate of insulin sensitivity (SI) and its daily variation are essential for optimizing insulin therapy in type 1 diabetes (T1D). Recently, a SI index based on continuous glucose monitoring (CGM) and insulin pump (CSII) data (SISP) has been validated in adults with T1D. Herein, we validated the SISP index against the oral minimal model (MM) one (SIMM) during two sequential meals in youth with T1D during hybrid closed-loop (HCL) treatment. Ten youths with T1D (4F; age=20.9±3.7 y; BMI=23.6±4.5 kg/m2; TDD= 50.6±16.3 U/day; HbA1c 7.3±0.6%) underwent two consecutive, standardized meal studies (breakfast, B, and lunch, L) while wearing the UVA-DiAS HCL (Dexcom CGM and t-slim CSII) system. Plasma glucose and insulin concentration data (measured every 10 min for 4 h during each meal) were used for SIMM estimation, while the corresponding CGM and CSII data, derived from the HCL system, were used for SISP calculation. SISP well correlated with SIMM (Fig. 1) for both B (18.1±7.6 vs. 21.5±12.1 10-4dL/kg/min per uU/mL, R=0.70) and L (26.5±10.1 vs. 26.0±13.8 10-4dL/kg/min per uU/mL, R=0.77). Between-meal (L-B) variation of SISP was also well correlated with its MM counterpart (R= 0.82). SISPis a reliable proxy of the oral minimal model derived SI and can be used to customize both open- and closed-loop treatments to improve glycemic outcomes in young people with T1D.

Disclosure

M. Schiavon: None. A. Galderisi: None. K.A. Kraemer: None. C. Cobelli: None. C. Dalla Man: None. E. Cengiz: Advisory Panel; Self; Abvance, ADOCIA, MannKind Corporation, Novo Nordisk Inc. Speaker's Bureau; Self; Novo Nordisk Inc.

Funding

JDRF (to E.C.); International Society for Pediatric and Adolescent Diabetes; Patterson Foundation (to A.G.); European Medical Information Framework (to A.G.); University of Padova (to M.S., C.D.M.)
1069-P: Safety and Efficacy of a Novel Basal-Bolus Insulin Delivery Device (IDD) in Adults with T2D Using Rapid-Acting or Regular Human Insulin
Authors: ARONSON RONNIE , MAHONEY EDWARD T. , SALIU DRILON , BERGQUIST LEYA , HIRSCH LAURENCE
Published: June 2019

Objective: To assess usability, 24-hour glycemic profiles, and safety of an investigational basal/bolus IDD in people with T2D transitioning from MDI.

Research Design and Methods: This single-center, open-label, two-period pilot study enrolled people with T2D and HbA1c 7-11%. Subjects continued their usual MDI therapy during a 2-3 -day in-clinic MDI period and then were switched to the IDD for a 6-day in-clinic IDD period, without changing insulin dose. Subjects wore blinded CGM throughout each in-clinic period.

Results: Twenty-one people (mean±SD age 57±8 years; HbA1c 8.2±0.9%) using U-100 insulin lispro (n=11) or U-100 regular human insulin RHI (n=10) were enrolled. Glycemic measures improved from the MDI to the IDD period, including FBG: 141.2 ± 38.3 mg/dl vs. 121.2 ± 35.0 mg/dl (P=0.002), respectively; 24-hour mean glucose: 137.0 ± 20.5 mg/dl vs.125.0 ± 16.5 mg/dl (P=0.004), and time-in-range (70-180 mg/dL): 81.0 ± 14.4% vs. 87.5 ± 10.6% (P=0.008). There were no significant differences between MDI and IDD for time in hypoglycemia (<70 mg/dL), CV%, nor mean of daily differences (MODD). Mean amplitude of glycemic excursions (MAGE) was significantly lower with IDD (P=0.011). There were no serious AEs. There were no significant differences between insulin lispro and RHI for any glycemic measures, within either phase. *Disclaimer: RHI is not approved for use in pumps. IDD not available for sale.

Conclusions: Results of this pilot study suggest that the IDD, used with insulin lispro or RHI, is as safe and effective for adults previously prescribed MDI therapy, without requiring dose change, in the short term. Administering either insulin lispro or RHI in the IDD led to similar glycemic responses and outcomes based on 24-hour glycemic profiles in people with T2D. To our knowledge, this is the first study to evaluate RHI in people with T2D using CGM for 24-hour glycemic profiles. Additional trials are warranted to further evaluate this novel IDD in larger populations.

Disclosure

R. Aronson: Research Support; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Senseonics. E.T. Mahoney: Employee; Self; Becton, Dickinson and Company. D. Saliu: Employee; Spouse/Partner; Allergan. Employee; Self; Becton, Dickinson and Company. L. Bergquist: Employee; Self; Becton, Dickinson and Company. L. Hirsch: Employee; Self; Becton, Dickinson and Company. Stock/Shareholder; Self; Merck & Co., Inc.