Taking the Long View: What Does a Child Focus Add to Social Protection?

Recognising that many indicators of vulnerability among children, such as malnutrition or poor educational performance, might reflect intergenerational problems has profound implications for the design and implementation of social protection programmes. Treating the symptoms of these problems is of course essential: a malnourished child needs immediate nutritional support and a child who is failing at school needs special attention. But the argument of this paper is that ‘taking the long view’ is imperative if the reasons why children are malnourished, or failing, are to be correctly identified and adequately addressed. Importantly, the analysis implies directing interventions not exclusively at the children who are at risk, but at others in society who are responsible for the care of children

Mislocalization of the E3 Ligase, beta-Transducin Repeat-containing Protein 1 (beta-TrCP1), in Glioblastoma Uncouples Negative Feedback between the Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase 1 (PHLPP1) and Akt

The PH domain leucine-rich repeat protein phosphatase, PHLPP, plays a central role in controlling the amplitude of growth factor signaling by directly dephosphorylating and thereby inactivating Akt. The cellular levels of PHLPP1 have recently been shown to be enhanced by its substrate, activated Akt, via modulation of a phosphodegron recognized by the E3 ligase β-TrCP1, thus providing a negative feedback loop to tightly control cellular Akt output. Here we show that this feedback loop is lost in aggressive glioblastoma but not less aggressive astrocytoma. Overexpression and pharmacological studies reveal that loss of the feedback loop does not result from a defect in PHLPP1 protein or in the upstream kinases that control its phosphodegron. Rather, the defect arises from altered localization of β-TrCP1; in astrocytoma cell lines and in normal brain tissue the E3 ligase is predominantly cytoplasmic, whereas in glioblastoma cell lines and patient-derived tumor neurospheres, the E3 ligase is confined to the nucleus and thus spatially separated from PHLPP1, which is cytoplasmic. Restoring the localization of β-TrCP1 to the cytosol of glioblastoma cells rescues the ability of Akt to regulate PHLPP1 stability. Additionally, we show that the degradation of another β-TrCP1 substrate, β-catenin, is impaired and accumulates in the cytosol of glioblastoma cell lines. Our findings reveal that the cellular localization of β-TrCP1 is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as β-catenin

Differential Expression of miRNAs in Colorectal Cancer: Comparison of Paired Tumor Tissue and Adjacent Normal Mucosa Using High-Throughput Sequencing

We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer. Although there is existing data of miRNA contribution to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to statistically test for differences in read counts per gene between samples: edgeR when using the pair information and DESeq when ignoring this information, i.e., treating tumor and normal samples as independent groups. We identify 37 miRNAs that are significantly dysregulated in both statistical approaches, 19 down-regulated and 18 up-regulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs, which to our knowledge have not previously been associated with colorectal carcinogenesis: the following significantly down-regulated miR-490-3p, -628-3p/-5p, -1297, -3151, -3163, -3622a-5p, -3656 and the up-regulated miR-105, -549, -1269, -1827, -3144-3p, -3177, -3180-3p, -4326. Although the study is preliminary with only eight patients included, we believe the results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis. As such the results would serve as a robust training set for validation of potential biomarkers in a larger cohort study. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon

Dimensão cuidadora da enfermagem e da família na assistência à criança hospitalizada: concepções da enfermagem Dimensión cuidadora de la enfermería y de la familia en la asistencia al niño hospitalizado: concepciones de la enfermería Dimension of nursing and family care to hospitalized children: conceptions of nursing

A dimensão e o modo de participação da família, no cuidado à criança hospitalizada, tem sido tema de estudo da enfermagem. O objetivo desta pesquisa foi analisar como está delineada a dimensão cuidadora da enfermagem e da família na assistência à criança hospitalizada. Trata-se de uma pesquisa qualitativa, realizada com a equipe de enfermagem de um hospital-escola, por meio de entrevista semiestruturada. A organização dos dados pautou-se na análise temática. Os resultados apontam que o trabalho realizado pela enfermagem está centrado em procedimentos; que a interação com a criança e sua família é tangencial no processo de cuidar; e que a família tem dividido cuidados com a equipe mas não tem sido compreendida como co-participante, tampouco incluída na perspectiva do cuidado. Defende-se que a criação de vínculo pode promover uma lógica do processo de trabalho, na perspectiva da integralidade e resgate da dimensão cuidadora da enfermagem.<br>A dimensión y el modo de participación de la familia, en el cuidado al niño hospitalizado, ha sido tema de estudios de la enfermería. El objetivo de esta investigación fue analizar como está delineada la dimensión cuidadora de la enfermería y de la familia en la asistencia al niño hospitalizado. Se trata de una investigación cualitativa, realizada con el equipo de enfermería de un hospital escuela, por medio de entrevistas semiestruturadas. La organización de los datos se orientó por el análisis temático. Los resultados apuntan que el trabajo realizado por la enfermería está centrado en procedimientos. La interacción con el niño y su familia es tangencial en el proceso de cuidar. La familia ha dividido los cuidados con el equipo y no ha sido entendida como copartícipe, también no ha sido incluida en la perspectiva del cuidado. Defendemos que la producción de un vínculo puede promover una lógica del proceso de trabajo en la perspectiva integradora y rescatar la dimensión cuidadora de la enfermería.<br>Family participation in the care of a hospitalized child, both regarding its forms and dimension, has been a theme of study in nursing. The objective of this study was to analyze the organization of both nursing care and family care to the hospitalized child. This qualitative research was performed using semi-structured interviews with nursing staff of a school-hospital. Theme analysis was used to guide data organization. The results show that nursing care focuses on procedures. Interaction with the children and their family is tangential to the caring process. Families have shared responsibilities with the staff but have not been recognized as a co-participant or been included into the caring perspective. Efforts should be made to create bonds to promote a logic regarding the process of work within the integrality perspective and to rescue the caring dimension of nursing