um cuidado especializado do enfermeiro obstetra

Observa-se, hoje em dia, que algumas práticas na maternidade tendem a ignorar as preferências das mulheres em trabalho de parto, uniformizando os cuidados com prejuízo para o bem-estar e a qualidade de vida das famílias. As práticas em Obstetrícia têm vindo a tornar-se cada vez mais repletas de intervenção, focando-se apenas nos resultados físicos (mortalidade e morbilidade) e descurando as vivências das parturientes e família, assim como as consequências psicossociais de um parto traumático. O presente Relatório de Estágio pretende refletir os cuidados em maternidade na perspetiva EEESMOG, que se visa holística, centrada no cliente e baseada na evidência. Da mesma forma, espelha as aprendizagens efetuadas em contexto do Estágio com Relatório inserido no 6º CMESMO da ESEL. Foram escolhidos como referenciais teóricos norteadores os modelos de Nola Pender – Modelo de Promoção da Saúde, e a Teoria de Empowerment em Saúde de Nelma Shearer. Foi também realizada uma Revisão Sistemática da Literatura que visou responder à seguinte questão de investigação: “Quais os cuidados do EEESMOG promotores do empowerment das mulheres direcionado para uma tomada de decisão informada relativa ao trabalho de parto?”. Adicionalmente, foi efetuado um registo da interação durante a prestação de cuidados no decorrer do estágio, sobre os quais foi efetuada uma reflexão e confrontação com os resultados da RSL. Concluiu-se que os cuidados que o EEESMOG presta que são promotores de uma tomada de decisão informada para o trabalho de parto se inserem dentro de três grandes temas, nomeadamente Competências da esfera relacional, Competências da esfera da prática clínica e Competências da esfera científica, com especial referência para os cuidados que se relacionam com o Estabelecimento de Relação Terapêutica, a Educação para a Saúde, o Cuidado da Mulher em trabalho de parto, a Promoção do exercício do Consentimento Informado e a Prática baseada na Evidência

Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents

<div><p>Leukemia is the most common pediatric malignancy, constituting more than 30% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and poor survival rates post relapse remain a challenge. Given this, more effective and innovative therapeutic strategies are needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for the regulation of several mitotic processes, have been identified as potential targets for cancer therapeutics. Elevated expression of Aurora kinases has been demonstrated in several malignancies and is associated with aberrant mitotic activity, aneuploidy and alterations in chromosomal structure and genome instability. Based on this rationale, a number of small molecule inhibitors have been formulated and advanced to human studies in the recent past. A comparative analysis of these agents in cytotoxicity and target modulation analyses against a panel of leukemia cells provides novel insights into the unique mechanisms and codependent activity pathways involved in targeting Aurora kinases, constituting a distinctive preclinical experimental framework to identify appropriate agents and combinations in future clinical studies.</p></div

Graphical representation of the IC₅₀ values of a panel of Aurora kinase inhibitors against leukemia cell lines, normal lymphocytes and bone marrow stroma presented inTable 2.

<p>The diverse sensitivity of each Aurora kinase inhibitor in this panel against B-ALL (C1, SEM, B1, UOCB1, Nalm6, KOPN8), T-ALL (CEM, Molt-3), AML (Molm13, MV4-11, TIB-202), APML (NB4, HL-60, HL-60RA) cell lines and normal lymphocytes and bone marrow stroma (BMS) is shown in graphs A-N. Each graph indicates IC₅₀ values in a tested range from 1×10⁻⁶ to 10 µM. Points at 1×10⁻⁶ µM represents IC₅₀ values of 1×10⁻⁶ µM or less and points at 10 µM represents IC₅₀ values of 10 µM or more. Values are calculated averages from three separate experiments ± standard deviations.</p

Analysis of the effect of Aurora kinase inhibitors on <i>in vitro</i> hematopoietic colony formation.

<p>Normal bone marrow derived CD34⁺ cells were incubated with increasing concentrations of Aurora A Inhibitor I (A), Hesperadin (B), ZM447439 (C), AT9283 (D) or DMSO in methylcellulose cultures containing cytokines to stimulate haematopoiesis. After 14 days in culture, myeloid and erythroid colonies were enumerated by counting under an inverted microscope based on morphology. Data presented here are representative of two separate experiments.</p

Summary of half maximal inhibitory concentration (IC₅₀) values for Aurora kinase inhibitors against pediatric and infant leukemia cell lines, normal lymphocytes and bone marrow stroma.

<p>Tumour cells from six B-ALL cell lines (C1, SEM, B1, UOCB1, Nalm6, KOPN8), two T-ALL cell lines (CEM, Molt-3), three AML cell lines (Molm13, MV4-11, TIB-202) and three APML cell lines (NB4, HL-60, HL-60 RA), as well as normal lymphocytes and bone marrow stroma, were treated with individual inhibitors at eight concentrations (1×10⁻⁶ to 10 µM). After four days in culture, cell viability was quantified by Alamar blue assay or automated microscopy and percent growth inhibition was determined by comparison to cells treated with DMSO control. The calculated IC₅₀ values ± standard deviations are representative of three separate experiments.</p

Aurora kinase inhibitors promote changes in Aurora kinase activity and induce cleavage of apoptotic markers in leukemia cell lines C1 and KOPN8.

<p>C1 and KOPN8 were treated with Aurora kinase inhibitors or vehicle control (DMSO) at 1 µM for 18 hours. The majority of the inhibitors tested induced dephosphorylation of one or more of the Aurora kinases, with the exception of Aurora-A Inhibitor I and ENMD-2076. Evidence of apoptosis is shown with increased cleavage of PARP and caspase 7 compared to vehicle control in all of the inhibitors tested, with the exception of JNJ-7706621 for both C1 and KOPN8 and ENMD-2076 for KOPN8. β-Actin was used as a loading control. Data presented are representative of three separate experiments.</p

Hesperadin promotes changes in phosphorylation of Aurora kinases and induces apoptosis in leukemia cell lines in a time dependent manner.

<p>C1, SEM, KOPN8 and TIB-202 were treated with 0.1 µM Hesperadin or corresponding DMSO control for 2, 4, 6, 12 or 24 hours. Western blot analysis indicates maintained phosphorylation of Aurora-A in all cell lines from 2 to 24 hours, with a slight increase in activity starting at 12 hours. In C1 and TIB-202, dephosphorylation of Aurora-B and Aurora-C was initiated at 2 hours and maintained until 24 hours. Similarly, in SEM and KOPN8, dephosphorylation of Aurora-B was initiated at 2 hours and maintained until 24 hours. Induction of apoptosis is indicated by the cleavage of PARP starting at 12 hours and the cleavage of caspase 7 starting at 4 hours for C1 and at 12 hours for SEM, KOPN8 and TIB-202. β-Actin was used as a loading control. Data presented are representative of three separate experiments.</p

Aurora kinase siRNA promotes changes in Aurora kinase phosphorylation and cleavage of apoptotic markers in leukemia cell lines SEM and TIB-202.

<p>SEM and TIB-202 were exposed to either Aurora-A siRNA, Aurora-B siRNA or negative control siRNA for 48 and 72 hours. Silencing of Aurora-A induced increased phosphorylation of Aurora-B at 72 hours in SEM. Comparatively, silencing of Aurora-A induced increased phosphorylation of Aurora-B and Aurora-C at both time points in TIB-202. Silencing of Aurora-B induced increased phosphorylation of Aurora-A compared to controls at both 48 and 72 hours in both cell lines. Silencing of either Aurora-A or Aurora-B induced PARP cleavage at both time points. Comparatively, caspase 7 cleavage was only evident following silencing of Aurora-B. β-Actin was used as a loading control. Data presented are representative of three separate experiments.</p

Aurora A Inhibitor I promotes changes in phosphorylation of Aurora kinases and induction of apoptosis in leukemia cell lines in a time dependent manner.

<p>C1, SEM, KOPN8 and TIB-202 were treated with 1 µM Aurora A Inhibitor I or corresponding DMSO control for 2, 4, 6, 12 or 24 hours. Western blot analysis indicates a slight increase in phosphorylation of Aurora-A at 12 and 24 hours for C1 and an initial decrease, followed by a subsequent increase in phosphorylation of Aurora-A starting at 4 hours for KOPN8 and 6 hours for both SEM and TIB-202. Both Aurora-B and Aurora-C gradually increased in phosphorylation starting at 6 hours for C1, 2 hours for SEM and KOPN8 and 4 hours for TIB-202. Induction of apoptosis is indicated by the cleavage of PARP and caspase 7 starting at 12 hours for C1, SEM and KOPN8 and 4 hours for TIB-202. β-Actin was used as a loading control. Data presented are representative of three separate experiments.</p

Summary of Aurora kinase inhibitors investigated in this study.

<p>The targets and corresponding IC₅₀ values for a panel of 14 Aurora kinase inhibitors are listed.</p