Fibrodisplasia ossificante progressiva em pediatria: revisão integrativa com foco na enfermagem / Progressive ossifying fibrodysplasia in pediatrics: an integrative review focusing on nursing / Fibrodisplasia osificante progresiva en pediatría: revisión integradora centrada en la enfermería

Objetivo: identificar as ações de cuidado/assistência de enfermagem ao paciente pediátrico com FOP na Atenção Primária à Saúde. Método: revisão integrativa, com as buscas realizadas em outubro de 2020, em cinco bases de dados e literatura cinzenta. Com descritores nacionais e internacionais. A seleção dos estudos foi realizada por revisores independentes. Resultados: a partir de uma busca ampla foram identificados 1213 estudos e incluídos 2 artigos na amostra final. Seguiu-se três direcionamentos temáticos assistenciais: Contribuições de enfermagem no reconhecimento precoce da doença, a importância da educação em saúde, e a prevenção de traumatismos. Conclusão: os resultados obtidos agregaram conhecimento acerca da assistência aos pacientes pediátricos com FOP. Estudos científicos acerca dos cuidados de enfermagem a essa doença ainda são escassos, assim recomenda-se o desenvolvimento de novos estudos visto a significância do papel da enfermagem às doenças raras (AU).

Objective: to identify the nursing care/assistance to pediatric patients with FOP in Primary Health Care. Method: integrative review was conducted in October 2020, in five databases and gray literature. With national and international descriptors. The eligibility of studies was performed by independent reviewers. Results: of 1213 potential studies, 2 studies were included in the final sample. Three thematic care directions followed: Nursing contributions to the early recognition of the disease, the importance of health education, and the prevention of injuries. Conclusion: The results obtained added knowledge about the assistance to pediatric patients with FOP. Scientific studies about nursing care for this disease are still scarce, so it is recommended that new studies be developed, given the significance of nursing's role in rare diseases (AU).

Objetivo: identificar las acciones de atención/asistencia de enfermería a pacientes pediátricos con FOP en la Atención Primaria de Salud. Método: revisión integradora, las búsquedas se realizaron en octubre de 2020, en cinco bases de datos y en la literatura gris, con descriptores nacionales e internacionales. La selección de los estudios fue realizada por revisores independientes. Resultados: mediante una búsqueda amplia se identificaron 1213 estudios y se incluyeron 2 artículos en la muestra final. Se siguieron tres direcciones temáticas de atención: aportes de la enfermería para el reconocimiento temprano de la enfermedad; importancia de la educación para la salud; y prevención de traumatismos. Conclusión: los resultados aportaron conocimiento adicional sobre la atención a pacientes pediátricos con FOP. Los estudios científicos sobre la atención de enfermería a esta enfermedad aún son escasos, por lo que se recomienda desarrollar nuevos estudios, dada la importancia que tiene el papel de la enfermería en las enfermedades raras (AU).

Perfil de morbidade pediátrica em um hospital público de ensino do Paraná / Profile of pediatric morbidity in a university teaching hospital of Paraná

O objetivo foi caracterizar as internações ocorridas em um serviço clínico pediátrico, de um hospital de ensino de Curitiba, Paraná. Estudo quantitativo, transversal, descritivo, utilizou dados secundários do sistema de informação hospitalar da instituição em estudo, com recorte às internações de crianças e adolescentes na Clínica Pediátrica, entre 2015 e 2017. Foram identificadas 491 internações no período, com proporções próximas entre os anos. A análise conclui: prevalência de internações do sexo feminino; em idade escolar; procedentes da 2ª Regional de Saúde do Paraná. Como causas das internações: neoplasias; doenças endócrinas, nutricionais e metabólicas; e, doenças do aparelho respiratório. Portanto, o perfil de morbidade contribui para a compreensão da transição epidemiológica. Conhecer as características das internações fornece subsídios para a gestão do serviço, favorecendo a qualidade da assistência à criança. (AU)

The objective of this study was to characterize hospitalizations of a pediatric clinical service in a teaching hospital in Curitiba, state of Paraná. This is a quantitative, cross-sectional, descriptive study, using secondary data from the hospital information system, focusing on hospitalizations of children and adolescents at the Pediatric Clinic, between 2015 and 2017. There were 491 hospitalizations in the period, with similar proportions within the years. The analysis concludes: prevalence of female hospitalizations; school-age individuals; from 2nd Regional Health Unit of Paraná. The causes of hospitalizations: Neoplasms; Endocrine, Nutritional, Metabolic and Respiratory Tract Diseases. Therefore, the morbidity profile contributes to the understanding of the epidemiological transition. Knowing the characteristics of hospitalizations provides subsidies for service management, favoring the quality of childcare. (AU)

p53-dependent repression of polo-like kinase-1 (PLK1).

PLK1 is a critical mediator of G2/M cell cycle transition that is inactivated and depleted as part of the DNA damage-induced G2/M checkpoint. Here we show that downregulation of PLK1 expression occurs through a transcriptional repression mechanism and that p53 is both necessary and sufficient to mediate this effect. Repression of PLK1 by p53 occurs independently of p21 and of arrest at G1/S where PLK1 levels are normally repressed in a cell cycle-dependent manner through a CDE/CHR element. Chromatin immunoprecipitation analysis indicates that p53 is present on the PLK1 promoter at two distinct sites termed p53RE1 and p53RE2. Recruitment of p53 to p53RE2, but not to p53RE1, is stimulated in response to DNA damage and/or p53 activation and is coincident with repression-associated changes in the chromatin. Downregulation of PLK1 expression by p53 is relieved by the histone deacetylase inhibitor, trichostatin A, and involves recruitment of histone deacetylase to the vicinity of p53RE2, further supporting a transcriptional repression mechanism. Additionally, wild type, but not mutant, p53 represses expression of the PLK1 promoter when fused upstream of a reporter gene. Silencing of PLK1 expression by RNAi interferes with cell cycle progression consistent with a role in the p53-mediated checkpoint. These data establish PLK1 as a direct transcriptional target of p53, independently of p21, that is required for efficient G2/M arrest.

Polo-like kinase-1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated p53 turnover.

The E3 ubiqutin ligase, murne double-minute clone 2 (MDM2), promotes the degradation of p53 under normal homeostatic conditions. Several serine residues within the acidic domain of MDM2 are phosphorylated to maintain its activity but become hypo-phosphorylated following DNA damage, leading to inactivation of MDM2 and induction of p53. However, the signalling pathways that mediate these phosphorylation events are not fully understood. Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (PLK1), phosphorylates MDM2 at one of these residues, Ser260, and stimulates MDM2-mediated turnover of p53. These data are consistent with the idea that deregulation of PLK1 during tumourigenesis may help suppress p53 function.

Phosphorylation of the acidic domain of Mdm2 by protein kinase CK2.

The Murine double-minute clone 2 (Mdm2) onco-protein is the principal regulator of the tumour suppressor, p53. Mdm2 acts as an E3-type ubiquitin ligase that mediates the ubiquitylation and turnover of p53 under normal, unstressed circumstances. In response to cellular stress, such as DNA damage, the Mdm2-p53 interaction is disrupted. Part of the mechanism of uncoupling p53 from Mdm2-mediated degradation involves hypo-phosphorylation of a cluster of phosphorylated serine residues in the central acidic domain of Mdm2. Here, we show that two of the residues within this domain that are phosphorylated in vivo, Ser-260 and Ser-269, are phosphorylated by CK2 in vitro. Treatment of cells with the CK2 inhibitor, 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), leads to the induction of p53 and downstream targets of p53 including Mdm2 itself and p21. These data are consistent with the idea that CK2-mediated phosphorylation of Mdm2 may regulate Mdm2-mediated p53 turnover.

Protein kinase CK1delta phosphorylates key sites in the acidic domain of murine double-minute clone 2 protein (MDM2) that regulate p53 turnover.

Murine double-minute clone 2 protein (MDM2) is an E3 ubiquitin ligase that regulates the turnover of several cellular factors including the p53 tumor suppressor protein. As part of the mechanism of p53 induction in response to DNA damage, a cluster of serine residues within the central acidic domain of MDM2 become hypophosphorylated, leading to attenuation of MDM2-mediated p53 destruction. In the present study, we identify the protein kinase CK1delta as a major cellular activity that phosphorylates MDM2. Amino acid substitution, coupled with phosphopeptide analyses, indicates that several serine residues in the acidic domain, including Ser-240, Ser-242, and Ser-246, as well as Ser-383 in the C-terminal region, are phosphorylated by CK1delta in vitro. We also show, through expression of a dominant negative mutant of CK1delta or treatment of cells with IC261, a CK1delta-selective inhibitor, that MDM2 is phosphorylated by CK1delta in cultured cells. These data establish the identity of a key signaling molecule that promotes the phosphorylation of a major regulatory region in MDM2 under normal growth conditions.

A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein.

MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro. Analysis of MDM2 in cultured cells confirms that Ser-166 and Ser-188 are phosphorylated by AKT in a physiological context.