[OurPuppet - Caring support with an interactive puppet for informal caregivers : Opportunities and challenges in the social and technical developmental process]. / OurPuppet ­ Pflegeunterstützung mit einer interaktiven Puppe für pflegende Angehörige : Chancen und Herausforderungen im sozialen und technischen Entwicklungsprozess.

BACKGROUND: The "OurPuppet" project comprises a sensor-based, interactive puppet that will be developed to communicate with people in need of care during a short period of absence of the informal caregiver. Specially qualified puppet guides will support the use of the new technical development. They instruct people with dementia and caregivers on how to use the puppet and supervise the (informal) care relationship through discussions on a regular basis. OBJECTIVES: The article shows the specific components of users' needs for which the concrete technical development should find answers. It also focuses on the opportunities and challenges for the technical and social developmental process accompanied by these demands. MATERIAL AND METHODS: The analysis of the users' needs is based on a participatory approach. Semi-structured focus group interviews were conducted with informal caregivers, nurses and volunteers in order to identify typical situations in home care settings. The interviews were paraphrased and summarized in order to deduce inductive categories (qualitative data analysis), which describe everyday situations that the technical system should address. RESULTS AND CONCLUSION: Such analyses provide information about the needs of potential users and indicate how to design such technical systems. Furthermore, opportunities and challenges of the development process as well as important contextual information were identified.

Oncofetal gene SALL4 in aggressive hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. METHODS: We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. RESULTS: SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. CONCLUSIONS: SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.).

Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex.

An exciting recent approach to targeting transcription factors in cancer is to block formation of oncogenic complexes. We investigated whether interfering with the interaction of the transcription factor SALL4, which is critical for leukemic cell survival, and its epigenetic partner complex represents a novel therapeutic approach. The mechanism of SALL4 in promoting leukemogenesis is at least in part mediated by its repression of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through its interaction with a histone deacetylase (HDAC) complex. In this study, we demonstrate that a peptide can compete with SALL4 in interacting with the HDAC complex and reverse its effect on PTEN repression. Treating SALL4-expressing malignant cells with this peptide leads to cell death that can be rescued by a PTEN inhibitor. The antileukemic effect of this peptide can be confirmed on primary human leukemia cells in culture and in vivo, and is identical to that of down-regulation of SALL4 in these cells using an RNAi approach. In summary, our results demonstrate a novel peptide that can block the specific interaction between SALL4 and its epigenetic HDAC complex in regulating its target gene, PTEN. Furthermore, targeting SALL4 with this approach could be an innovative approach in treating leukemia.

I-CARE-An Interaction System for the Individual Activation of People with Dementia.

I-CARE is a hand-held activation system that allows professional and informal caregivers to cognitively and socially activate people with dementia in joint activation sessions without special training or expertise. I-CARE consists of an easy-to-use tablet application that presents activation content and a server-based backend system that securely manages the contents and events of activation sessions. It tracks various sources of explicit and implicit feedback from user interactions and different sensors to estimate which content is successful in activating individual users. Over the course of use, I-CARE's recommendation system learns about the individual needs and resources of its users and automatically personalizes the activation content. In addition, information about past sessions can be retrieved such that activations seamlessly build on previous sessions while eligible stakeholders are informed about the current state of care and daily form of their protegees. In addition, caregivers can connect with supervisors and professionals through the I-CARE remote calling feature, to get activation sessions tracked in real time via audio and video support. In this way, I-CARE provides technical support for a decentralized and spontaneous formation of ad hoc activation groups and fosters tight engagement of the social network and caring community. By these means, I-CARE promotes new care infrastructures in the community and the neighborhood as well as relieves professional and informal caregivers.