Levantamento dos indicadores de risco para o desenvolvimento infantil em um programa de Atenção Primária à Saúde: uma perspectiva fonoaudiológica / Survey of risk indicators for child development in a Primary Health Care program: a speech-language pathology perspective / Encuesta de indicadores de riesgo para el desarrollo infantil en un programa de Atención Primaria de Salud: una perspectiva fonoaudiológica

Introdução: Fatores de risco para o desenvolvimento infantil podem ocasionar alterações na comunicação, como linguagem e fala, funções auditivas e estomatognáticas. O programa Bebê Precioso, inserido na atenção básica da cidade de Joinville, Santa Catarina, visa acompanhar recém-nascidos (RNs) e lactentes de 0 a 24 meses, egressos da Unidade Neonatal, com histórico de fatores de risco para as alterações no desenvolvimento global. Objetivo: Identificar os principais fatores de risco para o desenvolvimento infantil e relacionados à fonoaudiologia, de RNs e lactentes acompanhados por este programa de atenção primária à saúde. Método: Estudo retrospectivo de caráter descritivo, com análise quantitativa de dados de prontuários de RNs e lactentes atendidos no programa no período de março de 2019 a março de 2020. Resultados: A amostra do estudo foi composta por 58RNs e lactentes. Os fatores de risco mais frequentes foram a prematuridade (77,5%), baixo peso ao nascer (72,5%), alterações respiratórias (50%), asfixia perinatal (19%), hiperbilirrubinemia (13,8%), quadro de infecção grave (12%), malformações congênitas e síndromes genéticas (5,2%) e alterações neurológicas (5%). 53,5% dos RNs foram atendidos pelos discentes de fonoaudiologia. Destes, 61,3% apresentaram alterações fonoaudiológicas, sendo 42,1% na motricidade orofacial, 42,1% auditivas e 15,8% no desenvolvimento da linguagem. Conclusão: Os participantes do presente estudo, apresentaram fatores de risco para alterações fonoaudiológicas de linguagem, motricidade orofacial e habilidades auditivas. Enfatiza-se a importância do fonoaudiólogo em programas de follow-up.

Introduction: Risk factors for child development can cause changes in communication, such as language and speech, auditory and stomatognathic functions. The Bebê Precioso, inserted in primary care in the city of Joinville, Santa Catarina State, aims to monitor newborn children (NC) and infants aged 0 to 24 months, discharged from the Neonatal Unit, with a history of risk factors for changes in global development. Objective: To identify the main risk factors for child development and related to speech therapy, of newborn and infant children followed by this primary health care program. Method: Retrospective descriptive study, with quantitative analysis of data from medical records of NC and infants treated in the program from March 2019 to March 2020. Results: The study sample consisted of 58 NC and infants. The most frequent risk factors were prematurity (77.5%), low birth weight (72.5%), respiratory disorders (50%), perinatal asphyxia (19%), hyperbilirubinemia (13.8%), of severe infection (12%), congenital malformations and genetic syndromes (5.2%) and neurological alterations (5%). 53.5% of the NBs were attended by Speech-Language Pathology students. Of these, 61.3% presented speech-language disorders, being 42.1% in orofacial motricity, 42.1% auditory and 15.8% in language development. Conclusion: The participants of this study presented risk factors for speech-language disorders in language, orofacial motricity and auditory skills. The importance of the speech therapist in follow-up programs is emphasized.

Introducción: Los factores de riesgo para el desarrollo infantil pueden provocar cambios en la comunicación, como el lenguaje y el habla, las funciones auditivas y estomatognáticas. El programa Bebé Precioso, insertado en atención primaria en la ciudad de Joinville, Santa Catarina, tiene como objetivo acompañar a recién nacidos (RN) y lactantes de 0 a 24 meses, dados de alta de la Unidad Neonatal, con antecedentes de factores de riesgo de cambios en el desarrollo. global. Objetivo: Identificar los principales factores de riesgo para el desarrollo infantil y relacionados con la logopedia, de recién nacidos y lactantes monitoreados por el programa de Atención Primaria de Salud. Método: Estudio retrospectivo de carácter descriptivo, con análisis cuantitativo de los datos de las historias clínicas de los recién nacidos y lactantes atendidos en el programa de marzo de 2019 a marzo de 2020. Resultados: La muestra del estudio estuvo constituida por 58 recién nacidos y lactantes. Los factores de riesgo más frecuentes fueron prematurez (77,5%), bajo peso al nacer (72,5%), trastornos respiratorios (50%), asfixia perinatal (19%), hiperbilirrubinemia (13,8%), infección grave (12%), malformaciones congénitas y síndromes genéticos (5,2%) y trastornos neurológicos (5%). El 53,5% (n=31) de los recién nacidos fueron atendidos por estudiantes de logopedia. De estos, el 61,3% presentó trastornos del habla y el lenguaje, con el 42,1% en la motricidad orofacial, el 42,1% auditiva y el 15,8% en el desarrollo del lenguaje. Conclusión: Los participantes del presente estudio presentaron factores de riesgo para trastornos del habla y lenguaje, motricidad orofacial y habilidades auditivas. Se enfatiza la importancia del logopeda en los programas de seguimento.

Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2V617F driven cells.

Myeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have reported cytotoxic effects in cellular and murine models of MPN, but no consensus has been reached regarding the potency and efficacy of inhibitors of the IGF1R-related pathway in this context. In the present study, we compared the potency and efficacy of three inhibitors of IGF1R-related pathways in a JAK2V617F-driven cellular model. These inhibitors (NT157, OSI-906, and NVP-AEW54) present antineoplastic activity with similar efficacy in Ba/F3 JAK2V617F cells, with NT157 showing the greatest potency. Both the induction of apoptosis and reduction in cell proliferation were associated with the observed reduction in cell viability. Downregulation of JAK2/STAT signaling was an advantageous off-target effect of all three inhibitors. These preclinical studies reinforce the potential of the IGF1R-related pathway as a therapeutic target in MPN.

Phenformin increases early hematopoietic progenitors in the Jak2V617F murine model.

BACKGROUND: Myeloproliferative neoplasms (MPN) are disorders characterized by an alteration at the hematopoietic stem cell (HSC) level, where the JAK2 mutation is the most common genetic alteration found in classic MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis). We and others previously demonstrated that metformin reduced splenomegaly and platelets counts in peripheral blood in JAK2V617F pre-clinical MPN models, which highlighted the antineoplastic potential of biguanides for MPN treatment. Phenformin is a biguanide that has been used to treat diabetes, but was withdrawn due to its potential to cause lactic acidosis in patients. AIMS: We herein aimed to investigate the effects of phenformin in MPN disease burden and stem cell function in Jak2V617F-knockin MPN mice. RESULTS: In vitro phenformin treatment reduced cell viability and increased apoptosis in SET2 JAK2V67F cells. Long-term treatment with 40 mg/kg phenformin in Jak2V617F knockin mice increased the frequency of LSK, myeloid progenitors (MP), and multipotent progenitors (MPP) in the bone marrow. Phenformin treatment did not affect peripheral blood counts, spleen weight, megakaryocyte count, erythroid precursors frequency, or ex vivo clonogenic capacity. Ex vivo treatment of bone marrow cells from Jak2V617F knockin mice with phenformin did not affect hematologic parameters or engraftment in recipient mice. CONCLUSIONS: Phenformin increased the percentages of LSK, MP, and MPP populations, but did not reduce disease burden in Jak2V617F-knockin mice. Additional studies are necessary to further understand the effects of phenformin on early hematopoietic progenitors.

NT157, an IGF1R-IRS1/2 inhibitor, exhibits antineoplastic effects in pre-clinical models of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is successfully treated with BCR-ABL1 tyrosine kinase inhibitors, but a significant percentage of patients develop resistance. Insulin receptor substrate 1 (IRS1) has been shown to constitutively associate with BCR-ABL1, and IRS1-specific silencing leads to antineoplastic effects in CML cell lines. Here, we characterized the efficacy of NT157, a pharmacological inhibitor of IGF1R-IRS1/2, in CML cells and observed significantly reduced cell viability and proliferation, accompanied by induction of apoptosis. In human K562 cells and in murine Ba/F3 cells, engineered to express either wild-type BCR-ABL1 or the imatinib-resistant BCR-ABL1T315I mutant, NT157 inhibited BCR-ABL1, IGF1R, IRS1/2, PI3K/AKT/mTOR, and STAT3/5 signaling, increased CDKN1A, FOS and JUN tumor suppressor gene expression, and reduced MYC and BCL2 oncogenes. NT157 significantly reduced colony formation of human primary CML cells with minimal effect on normal hematopoietic cells. Exposure of primary CML cells harboring BCR-ABL1T315I to NT157 resulted in increased apoptosis, reduced cell proliferation and decreased phospho-CRKL levels. In conclusion, NT157 has antineoplastic effects on BCR-ABL1 leukemogenesis, independent of T315I mutational status.

Nutrient requirements and evaluation of equations to predict chemical body composition of dairy crossbred steers.

OBJECTIVE: Objectives were to estimate energy and protein requirements of dairy crossbred steers, as well as to evaluate equations previously described in the literature (HH46 and CS16) to predict the carcass and empty body chemical composition of crossbred dairy cattle. METHODS: Thirty-three Holstein × Zebu steers, aged 19 ± 1 months old, with an initial shrunk body weight of 324 ± 7.7 kg, were randomly divided into three groups: reference group (n = 5), maintenance level (1.17% BW; n = 4), and the remaining 24 steers were randomly allocated to 1 of 4 treatments. Treatments were: intake restricted to 85% of ad libitum feed intake for either 0, 28, 42, or 84 d of an 84-d finishing period. RESULTS: The net energy and the metabolizable protein requirements for maintenance were 0.083 Mcal/EBW0.75/d and 4.40 g/EBW0.75, respectively. The net energy (NEG) and protein (NPG) requirements for growth can be estimated with the following equations: NEG (Mcal/kg EBG) = 0.2973(± 0.1212) × EBW0.4336(± 0.1002) and NPG (g/d) = 183.6(± 22.5333) × EBG - 2.0693(± 4.7254) × RE, where EBW = empty body weight, EBG = empty body gain, and RE = retained energy. Crude protein (CP) and ether extract (EE) chemical contents in carcass, and all the chemical components in the empty body were precisely and accurately estimated by CS16 equations. However, water content in carcass was better predicted by HH46 equation. CONCLUSION: The equations proposed in this study can be used for estimating the energy and protein requirements of crossbred dairy steers. The CS16 equations were the best estimator for CP and EE chemical contents in carcass, and all chemical components in the empty body of crossbred dairy steers, whereas water in carcass was better estimated using the HH46 equations.

NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2V617F-positive myeloproliferative neoplasm cells.

Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms (MPN); in this pathway, IRS2 is involved in the malignant transformation induced by JAK2V617F, and upregulation of IGF1R signaling induces the MPN phenotype. NT157, a synthetic compound designed as an IGF1R-IRS1/2 inhibitor, has been shown to induce antineoplastic effects in solid tumors. Herein, we aimed to characterize the molecular and cellular effects of NT157 in JAK2V617F-positive MPN cell lines (HEL and SET2) and primary patient hematopoietic cells. In JAK2V617F cell lines, NT157 decreased cell viability, clonogenicity, and cell proliferation, resulting in increases in apoptosis and cell cycle arrest in the G2/M phase (p < 0.05). NT157 treatment inhibited IRS1/2, JAK2/STAT, and NFκB signaling, and it activated the AP-1 complex, downregulated four oncogenes (CCND1, MYB, WT1, and NFKB1), and upregulated three apoptotic-related genes (CDKN1A, FOS, and JUN) (p < 0.05). NT157 induced genotoxic stress in a JAK2/STAT-independent manner. NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients (p < 0.05). These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.

IGF1R/IRS1 targeting has cytotoxic activity and inhibits PI3K/AKT/mTOR and MAPK signaling in acute lymphoblastic leukemia cells.

The IGF1R/IRS1 signaling is activated in acute lymphoblastic leukemia (ALL) and can be targeted by the pharmacological inhibitors NT157 (IGF1R-IRS1/2 inhibitor) and OSI-906 (IGF1R/IR inhibitor). Here we investigate the cellular and molecular effects of NT157 and OSI-906 in ALL cells. NT157 and OSI-906 treatment reduced viability, proliferation and cell cycle progression in ALL cell lines. Similarly, in primary samples of patients with ALL, both OSI-906 and NT157 reduced viability, but only NT157 induced apoptosis. NT157 and OSI-906 did not show cytotoxicity in primary samples from healthy donor. NT157 and OSI-906 significantly decreased Jurkat cell migration, but did not modulate Namalwa migration. Consistent with the more potent effect of NT157 on cells, NT157 significantly modulated expression of 25 genes related to the MAPK signaling pathway in Jurkat cells, including oncogenes and tumor suppressor genes. Both compounds inhibited mTOR and p70S6K activity, but only NT157 inhibited AKT and 4-EBP1 activation. In summary, in ALL cells, NT157 has cytotoxic activity, whereas OSI-906 is cytostatic. NT157 has a stronger effect on ALL cells, and thus the direct inhibition of IRS1 may be a potential therapeutic target in ALL.

Leaf count overdispersion in coffee seedlings / Superdispersão relacionado a contagem de folhas em mudas de cafeeiro

ABSTRACT: Coffee crops play an important role in Brazilian agriculture, with a high level of social and economic participation resulting from the jobs created in the supply chain and from the income obtained by producers and the revenue generated for the country from coffee bean export. In coffee plant growth, leaves have a determinant role in higher production; therefore, the leaf count per plant provides relevant information to producers for adequate crop management, such as foliar fertilizer applications. To describe count data, the Poisson model is the most commonly employed model; when count data show overdispersion, the negative binomial model has been determined to be more adequate. The objective of this study was to compare the fitness of the Poisson and negative binomial models to data on the leaf count per plant in coffee seedlings. Data were collected from an experiment with a randomized block design with 30 treatments and three replicates and four plants per plot. Data from only one treatment, in which the number of leaves was counted over time, were employed. The first count was conducted on 8 April 2016, and the other counts were performed 18, 32, 47, 62, 76, 95, 116, 133, and 153 days after the first evaluation, for a total of ten measurements. The fitness of the models was assessed based on deviance values and simulated envelopes for residuals. Results of fitness assessment indicated that the Poisson model was inadequate for describing the data due to overdispersion. The negative binomial model adequately fitted the observations and was indicated to describe the number of leaves of coffee plants. Based on the negative binomial model, the expected relative increase in the number of leaves was 0.9768% per day.

RESUMO: A cultura do café desempenha papel relevante na agricultura do Brasil, com expressiva participação social e econômica tanto pelos empregos gerados na cadeia produtiva, bem como pela renda obtida pelos produtores e pelas divisas geradas para o país na exportação do grão. No crescimento das plantas de café, as folhas desempenham papel decisivo para que tenha maior produção, portanto a contagem do número de folhas por planta fornece informações importantes aos produtores para o manejo adequado da cultura como, por exemplo, a aplicação de adubações foliares. Em geral, na descrição de dados obtidos por contagem, o modelo mais utilizado é o Poisson, sendo que quando os dados apresentam superdispersão, o modelo Binomial Negativo tem se mostrado mais adequado. O objetivo deste trabalho foi comparar o ajuste dos modelos de Poisson e Binomial Negativo em dados de contagens do número de folhas por planta em mudas do cafeeiro. Os dados foram obtidos de um experimento usando o delineamento em blocos casualizados com trinta tratamentos e três repetições com quatro plantas por parcela. Foram utilizados os dados de apenas um tratamento no qual foi feita a contagem do número de folhas ao longo do tempo. A primeira avaliação foi feita em 8 de abril de 2016 e as demais aos 18, 32, 47, 62, 76, 95, 116, 133 e 153 dias após a primeira avaliação, totalizando dez medidas. A adequação dos mesmos foi verificada com base nos valores da Deviance e no envelope simulado para os resíduos. Os resultados do ajuste indicaram que o modelo Poisson foi inadequado para descrição dos dados devido a superdispersão. O modelo Binomial Negativo se ajustou adequadamente e foi indicado para descrever o número de folhas das plantas do cafeeiro. Com base no modelo Binomial Negativo o aumento relativo esperado para o número de folhas foi de 0,9768% para cada dia.

Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis.

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

Micro-computed Tomography Shaping Ability Assessment of the New Blue Thermal Treated Reciproc Instrument.

INTRODUCTION: The present study aimed to assess canal preparation outcomes achieved by the new Reciproc Blue instrument using micro-computed tomography technology. M-Wire Reciproc was used as a reference instrument for comparison. METHODS: Seven pair-matched mesial roots of mandibular molars presenting similar anatomic features of the canal (length, volume, surface area, and configuration) were selected after scanning procedures and assigned to 1 of the 2 groups according to the instrument used, M-Wire Reciproc and Reciproc Blue. After canal instrumentation, the specimens were rescanned, and the registered preoperative and postoperative datasets were examined to evaluate the percentages of removed dentin, untouched canal walls, and degree of canal transportation. Comparisons regarding the above outcomes between the 2 groups were done by using paired t test with the alpha-type set at 5%. RESULTS: Root canals prepared with conventional M-Wire Reciproc or Reciproc Blue were found to present similar shaping properties with no significant differences in the tested parameters. CONCLUSIONS: M-Wire Reciproc and Blue Reciproc presented similar shaping outcomes.

Metformin exerts multitarget antileukemia activity in JAK2V617F-positive myeloproliferative neoplasms.

The recurrent gain-of-function JAK2V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2V617F-positive cells. In JAK2V617F-expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2V617F tumor burden and splenomegaly in Jak2V617F knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.

Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

Saúde do homem: os motivos da procura dos homens pelos serviços de saúde / Men's health: the reasons for men to reach out to health services

Objetivo: identificar os motivos pelos quais os homens procuram os serviços de saúde. Método: estudo qualitativo, exploratório, com coleta de dados efetivada por revisão narrativa e entrevista semiestruturada com 29 homens. As entrevistas foram submetidas à técnica de Análise de Conteúdo. Resultados: emergiram quatro categorias de análise: dor, incapacidade para o trabalho, prevenção e influência da esposa. As falas demonstram visivelmente e reforçam a ideia de que o homem procura o serviço de saúde em eventos agudos, especialmente, em caso de dor. Existe, por parte do homem, uma resistência ao autocuidado, ou seja, a não busca pelo serviço de saúde de forma preventiva e rotineira. Conclusão: o estereótipo do ser masculino e acultura de invulnerabilidade ainda criam resistência à adoção de práticas de autocuidado pelo homem.

Paclitaxel induces Stathmin 1 phosphorylation, microtubule stability and apoptosis in acute lymphoblastic leukemia cells.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by abnormal proliferation and accumulation of lymphoblasts in the hematopoietic system. Stathmin 1 is a proliferation marker for normal lymphocytes, which has been described as highly expressed in ALL patients and functionally important for leukemia phenotype. In the present study, we expand our previous observations and aim to investigate Stathmin 1 expression and its impact on laboratory features and clinical outcomes in an independent cohort of ALL patients, and to verify the effects of paclitaxel treatment on Stathmin 1 phosphorylation and cell viability in ALL cell lines. In ALL patients, Stathmin 1 expression was significantly increased, associated with lower age onset and positively correlated with white blood cell counts, but did not impact on clinical outcomes. Functional assays revealed that paclitaxel induces Stathmin 1 phosphorylation at serine 16 (an inhibitory site), microtubule stability and apoptosis in Jurkat and Namalwa cell lines. Paclitaxel treatment did not modulate cell viability of normal peripheral blood leukocytes. In conclusion, our data confirm increased levels of Stathmin 1 in ALL patients and that therapeutic doses of paclitaxel inhibits Stathmin 1 function and promote microtubule stability and apoptosis in ALL cells.

IRS1/ß-Catenin Axis Is Activated and Induces MYC Expression in Acute Lymphoblastic Leukemia Cells.

Insulin-like growth factor 1 (IGF1) and its receptor IGF1R regulate normal cell growth and contribute to cell transformation through activation of downstream signaling pathways. In fibroblast cells, insulin receptor substrate 1 (IRS1), through IGF1 signaling, was found to be the key protein for nuclear translocation of ß-catenin and MYC transcription activation. We herein investigated the IRS1/ß-catenin axis in acute lymphoblastic leukemia (ALL) cells. Samples were obtained from 45 patients with ALL and 13 healthy donors. ALL cell lines were used. Gene expression was measured by quantitative PCR. Protein expression, associations, and cellular localization were evaluated by immunoprecipitation, subcellular fractionation, and confocal microscopy. Cells were submitted to IGF1 stimulation and/or IGF1R pharmacological inhibition (OSI-906). IRS1, ß-catenin, and MYC mRNA expression were significantly elevated in ALL patients, compared to normal controls. MYC mRNA expression positively correlated with ß-catenin and IRS1. Increased age and MYC expression negatively affected overall survival by univariate analysis. Total and phospho-IGF1R and IRS1, MYC and ß-catenin protein expression were higher in ALL cells, compared to normal peripheral blood mononuclear cells (PBMC). IRS1 and ß-catenin were found to be colocalized in the nuclei and the cytoplasm of ALL cell lines, whereas both proteins were only slightly detected in the cytoplasm of normal PBMC. In Jurkat cells, a constitutive IRS1 and ß-catenin protein interaction were observed; OSI-906 treatment decreased IGF1R tyrosine phosphorylation, IRS1 expression and phosphorylation, nuclear translocation of ß-catenin, IRS1 and ß-catenin association, and MYC protein expression. In conclusion, the IRS1/ß-catenin axis is activated in ALL cells. J. Cell. Biochem. 118: 1774-1781, 2017. © 2016 Wiley Periodicals, Inc.

Avaliação do nível estresse de mães de pré-termo em hospital universitário / Evaluation of the stress level of preterm mothers in a university hospital

O estresse de mães de Recém-Nascidos Prematuros (RNPT) propicia maior insegurança no cuidado ao filho. Avaliar os níveis de estresse dessas mães frente à prematuridade contribui para propor intervenções de enfermagem adequadas que possibilitem o desenvolvimento da autoconfiança materna saudável e interação com o filho. Objetivou-se identificar o nível de estresse de mães de RNPT hospitalizados na Unidade de Terapia Intensiva Neonatal (UTIN). Estudo quantitativo, desenvolvido na UTIN de um hospital universitário, que aplicou a escala de mensuração de estresse -Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU), validada no Brasil em 2009, à20 mães de abril a julho de 2014. Análises foram realizadas no programa XLStat 2014, nível de significância assumido em todos os testes foi igual a 0,05.Este instrumento mede o estresse em três subescalas: sons e imagens; aparência e comportamento do bebê e alteração do papel dos pais. O nível de estresse encontrado foi muito estressante(3,8), principalmente na subescala alteração do papel dos pais (4,3). PSS:NICU é ferramenta válida para avaliar o estresse, demonstrando que mães mais jovens, primíparas e com RNPT extremos são mais vulneráveis. Deve-se ter um olhar distinto para suas necessidades ampliando a competência e segurança materna ao prover o cuidado ao filho.

The stress of mothers of Preterm Newborns (PTNB) provides great insecurity concerning the care towards their infant. Assessing the stress level of these mothers facing the prematurity contributes to propose appropriate nursing interventions that help to developthe healthy maternal self-confidence and also the interaction with the infant. The objective was to identify the stress level of mothers of PTNB hospitalized in the Neonatal Intensive Care Unit (NICU). This is a quantitative research, developed in the NICU of a University Hospital, that used the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU), validated in Brazil in 2009, with 20 mothers from April to July, 2014. Some analyses were carried in the program XLStat 2014, the level of significance for all the tests were 0,05. This tool measures the stress in three subscales: sounds and images; infant's behavior and appearance, and alteration in the parental role. The stress level found was very high (3,8), mainly in the subscale alteration of the parental role (4,3). PSS:NICU is an effective tool to evaluate thestress, demonstrating that younger, primipara and with extreme PTNB mothers are more vulnerable. They must receive a special look at their needs enlarging the competency and maternal security when providing care towards the infant.