Ankhd1 Silencing Inhibits Stathmin 1 Activity, Cell Proliferation And Migration Of Leukemia Cells

ANKHD1 is highly expressed in human acute leukemia cells and potentially regulates multiple cellular functions through its ankyrin-repeat domains. In order to identify interaction partners of the ANKHD1 protein and its role in leukemia cells, we performed a yeast two-hybrid system screen and identified SIVA, a cellular protein known to be involved in proapoptotic signaling pathways. The interaction between ANKHD1 and SIVA was confirmed by co-imunoprecipitation assays. Using human leukemia cell models and lentivirus-mediated shRNA approaches, we showed that ANKHD1 and SIVA proteins have opposing effects. While it is known that SIVA silencing promotes Stathmin 1 activation, increased cell migration and xenograft tumor growth, we showed that ANKHD1 silencing leads to Stathmin 1 inactivation, reduced cell migration and xenograft tumor growth, likely through the inhibition of SIVA/Stathmin 1 association. In addition, we observed that ANKHD1 knockdown decreases cell proliferation, without modulating apoptosis of leukemia cells, while SIVA has a proapoptotic function in U937 cells, but does not modulate proliferation in vitro. Results indicate that ANKHD1 binds to SIVA and has an important role in inducing leukemia cell proliferation and migration via the Stathmin 1 pathway. ANKHD1 may be an oncogene and participate in the leukemia cell phenotype.18533583593Stone, R.M., O'Donnell, M.R., Sekeres, M.A., Acute myeloid leukemia, Hematology (2004) Am. Soc. Hematol. Educ. 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Profundidade de semeadura e crescimento inicial de espécies forrageiras utilizadas para cobertura do solo Depth of sowing and initial growth of forage species used for soil coverage

O uso do consórcio entre plantas de cobertura e culturas anuais, no Cerrado, tem sido prática cada vez mais difundida, pela possibilidade de implantação das forrageiras durante o desenvolvimento das culturas anuais, através da diferença de profundidade e sistema de semeadura. Objetivou-se, neste trabalho avaliar a emergência e algumas características agronômicas de quatro espécies de plantas de cobertura, em diferentes profundidades, visando ao seu emprego na consorciação e sobressemeadura em culturas anuais. O experimento foi conduzido em casa-de-vegetação, no delineamento experimental de blocos ao acaso, em arranjo fatorial 4 x 7, composto pelas plantas de cobertura Brachiaria brizantha, B. decumbens, B. ruziziensis e Panicum maximum cv. Tanzânia, e por seis profundidades de semeadura e um sistema de cobertura de sementes (0 sem cobertura, 0 com cobertura, 1, 4, 8, 10 e 15 cm). As sementes foram semeadas em vasos e as plantas cultivadas por 40 dias. Avaliou-se o índice e o tempo de emergência, a altura de plantas, a fitomassa verde e seca da parte aérea, a área foliar, a fitomassa seca radicular e a densidade de comprimento radicular. O maior desenvolvimento das plantas estudadas foi detectado nas semeaduras até 1 cm de profundidade. O P. maximum não apresentou aptidão para uso em consórcio com culturas anuais.Não se recomenda a semeadura das plantas de cobertura a partir de 10 cm.<br>The use of the consortium between cover crops and annual crops in the Cerrado, is an increasingly widespread practice, because of the possibility of deployment of cover crops during the development of annual crops by the difference in depth and seeding system. The objective was to evaluate the emergency and some agronomic characteristics of four species of cover crops at different seeding depths, to use them in consortium and oversown in annual crops. The experiment was conducted in a greenhouse, and the experimental design of randomized blocks in factorial arranged 4 x 7, where it was four cover crops: Brachiaria brizantha, B. decumbens, B. ruziziensis and Panicum maximum cv. Tanzania, and six depths of sowing and a cover of seed system (0 cm without any mulch, 0 cm with a mulch of soybean leaves, 1, 4, 8, 10 and 15 cm). The cover crops were cropped in vase for 40 days. We evaluated emergence index, emergence time, plant height, green biomass and dry biomass of the above-ground part, leaf area, root dry biomass and root length density. The largest development of the cover crops was detected in the sowing up to 1 cm of depth. The P. maximum showed no ability to use in consortium with annual crops. The sowing of the cover crops from 10 cm is not recommended

Orientação sexual para jovens adultos com deficiência auditiva Sexual orientation for young adults with hearing impairments

o estudo investigou o tema da sexualidade junto a 14 jovens adultos com deficiência auditiva de 18 a 35 anos de idade, no Centro de Distúrbios da Audição Linguagem e Visão (CEDALVI) que faz parte do HRAC-USP/Bauru. Os objetivos foram: identificar quais as necessidades de informação no que diz respeito à sexualidade; intervir, através de um programa de orientação sexual, informando e discutindo sobre temas referentes à sexualidade e verificar a aquisição de informação obtida com o programa de orientação sexual. Para tal, foi realizado um programa de orientação sexual, com três encontros abordando os seguintes temas: Órgãos sexuais e relações de gênero, Relacionamento afetivo e Gravidez, doenças sexualmente transmissíveis e auto-estima. Utilizou-se para a coleta dos dados um questionário inicial, questionários com questões fechadas, falso e verdadeiro, tipo pré e pós-teste no início e ao final de cada encontro e uma entrevista de avaliação processual, ao final do programa. Observou-se que o termo sexualidade continua sendo reduzido ao ato sexual ou as formas de prevenção de doenças ou métodos contraceptivos por grande parte dos jovens e a fonte de informação mais citada foi a mídia. O tema de maior número de acertos no pós-teste foi Órgãos sexuais e relações de gênero e todos, em geral, avaliaram positivamente a participação no programa. Concluiu-se que é necessário que a sexualidade seja cada vez mais incluída em programas de reabilitação, garantindo o acesso a informação e a discussão do tema, tão importante na vida desses jovens.<br>the study investigated the theme of sexuality among 14 hearing impaired young adults, aged 18 to 35 years, at the Center for Hearing, Language and Visual Disturbances (CEDALVI), a service of the HRAC-USP/Bauru. The aims were: to identify what kinds of information on sexuality were needed; to intervene through a sexual orientation program, so as to inform and discuss themes related to sexuality and to assess the information obtained by means of the sexual education program. To this end, a sexual orientation program was set up with three sessions concerning the following themes: Sexual organs and gender relationships, Caring relationships and Pregnancy, sexually transmitted diseases and self-esteem. Data was collected through a first time questionnaire, with closed true and false questions, with pre and post-tests applied at the beginning and the end of each meeting, followed by interviews to evaluate the whole process at the end of the program. The results showed that most young adults still view the term sexuality as restricted to sexual intercourse or to prevention of sexually transmitted diseases or to contraceptive methods and the media was cited as the main source of information. In the post-test, the greatest number of correct responses occurred for the theme Sexual organs and gender relationships; in general, all participants offered positive reviews for participation in the program. The conclusion was that it is paramount to include sexual orientation in rehabilitation programs, guaranteeing access to information and promoting discussion of such subjects in these young people's lives

Sexualidade e deficiência intelectual: narrativas de pais de adolescentes Sexuality and intellectual handicap: parents' narratives

Pelo senso comum, adolescentes com deficiência intelectual têm a sexualidade exacerbada ou são assexuados. Para conhecer como vivenciam as manifestações sexuais de seus filhos, entrevistamos 14 pais de adolescentes com essa deficiência. A análise das narrativas obtidas foi baseada em autores da antropologia. Nelas, observaram-se os preconceitos e o desconhecimento sobre o tema, bem como a reprodução da ideologia de gênero da nossa sociedade. Nas narrativas dos pais de adolescentes do sexo masculino, a masturbação, a relação sexual e o medo de abuso sexual foram destaques, enquanto nas dos pais das adolescentes privilegiaram-se como tema as mudanças corporais e também o receio de que fossem abusadas sexualmente. A inadequação entre desenvolvimento físico e um comportamento sexual considerado socialmente impróprio também foi alvo de narrativas. Aponta-se a necessidade de ampliação do debate com os adolescentes, seus pais e diversos setores da sociedade para minimizar os preconceitos em relação à sexualidade das pessoas com deficiência intelectual, propiciando a garantia de seus direitos sexuais.<br>By common sense, adolescents with intellectual disabilities have a heightened sexuality or are asexual. To learn how they experience the sexual manifestations of their children, we interviewed 14 parents of adolescents with this deficiency. The analysis of the narratives obtained was based on authors of anthropology. In them, there were prejudices and ignorance on the subject, as well as playing the gender ideology of our society. In the narratives of parents of adolescent males, masturbation, sex and fear of sexual abuse were highlighted, while parents privileged themes such as bodily changes and also the fear that they were sexually abused. The mismatch between physical development and sexual behavior considered socially improper was also the target of narratives. The paper points up the need to expand the discussion with teens, their parents and various sectors of society to minimize biases regarding sexuality of people with intellectual disabilities, providing a guarantee of their sexual rights

Parâmetros genéticos e fenotípicos do desempenho reprodutivo de fêmeas Chianina Genetic and phenotypic parameters of reproductive performance of Chianina females

Objetivou-se estimar os parâmetros genéticos e fenotípicos de características reprodutivas de fêmeas bovinas da raça Chianina criadas em diferentes rebanhos participantes da Associazione Nazionale Allevatori Bovini Italiani da Carne (ANABIC). As características estudadas foram idade ao primeiro parto (IPP), primeiro intervalo de partos (IDP1) e intervalo médio de partos (IMDP). As análises estatísticas foram realizadas pelo procedimento General Linear Model (GLM) do programa estatístico SAS (Statistical Analysis System) e os componentes de variância foram estimados pelo método de máxima verossimilhança restrita utilizando-se o software MTDFREML sob modelo animal. Os números de observações utilizados para IPP, IDP1 e IMDP foram, respectivamente, 31.023; 23.998 e 94.497 e as médias encontradas, em dias, 1.037,69 &plusmn; 186,37; 457,93 &plusmn; 96,80 e 436,26 &plusmn; 90,83 para IPP, IDP1, IDPM. Todas as características avaliadas foram influenciadas pelo rebanho. Verificou-se efeito de estação e ano de nascimento da vaca sobre a IPP. O IDP1 e o IDPM foram influenciados por rebanho, estação e ano do parto precedente, observando-se efeito também da ordem de parição sobre o IDPM. As estimativas de herdabilidade para IPP, IDP1 e IDPM foram, respectivamente de 0,36 &plusmn; 0,014; 0,13 &plusmn; 0,014 e 0,05 &plusmn; 0,004. A repetibilidade para IDPM foi de 0,075 &plusmn; 0,004. A utilização de IPP e IDP1 em programas de melhoramento genético pode resultar em maior precocidade e mais alto potencial para longevidade nestes rebanhos.<br>ABSTRACT This study aimed to evaluate the reproductive performance of Chianina cows born from 1977 to 2002. Data was used to calculate age at first calving (AFC), first calving interval (CI1) and average calving intervals (avgCIs) for the whole lifetime of cows. After editing data, the number of records used for AFC, CI1 and avgCIs analyses were respectively 31,023; 23,998 and 94,497 respectively. Statistical analyses were done using the SAS program (Statistical Analysis System) and variance components were estimated by REML using the software MTDFREML fitting animal models. Means for AFC, CI1 and avgCIs were 1,037.69 &plusmn; 186.37, 457.93 &plusmn; 12.22 and 436,26 &plusmn; 12,17 days, respectively. Heritability estimates for AFC, CI1 and avgCIs were respectively 0.36 &plusmn; 0.014; 0.13 &plusmn; 0.014 e 0.05&plusmn;0.004 and the repeatability for avgCIs was 0.075 &plusmn; 0.004. The use of AFC and CI1 in genetic improvement programs may lead to an increase in precocity and potential longevity. Changes in management of females may decrease avgCIs, leading to higher and faster improvement in reproductive efficiency

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial

ImportanceLocoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. ObjectiveTo assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. Design, Setting, and ParticipantsThis multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. InterventionsPatients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. Main Outcomes and MeasuresThe primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. ResultsA total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P=.48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). Conclusions and RelevanceThis study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. Trial RegistrationClinicalTrials.gov identifier: NCT01345669Experimentele farmacotherapi