Externalising moods and psychological states in a cloud based system to enhance a pet-robot and child’s interaction

Background:This PATRICIA research project is about using pet robots to reduce pain and anxiety in hospitalized children. The study began 2 years ago and it is believed that the advances made in this project are significant. Patients, parents, nurses, psycholo- gists, and engineers have adopted the Pleo robot, a baby dinosaur robotic pet, which works in different ways to assist children during hospitalization. Methods: Focus is spent on creating a wireless communication system with the Pleo in order to help the coordinator, who conducts therapy with the child, monitor, under- stand, and control Pleo’s behavior at any moment. This article reports how this techno- logical function is being developed and tested. Results: Wireless communication between the Pleo and an Android device is achieved. The developed Android app allows the user to obtain any state of the robot without stopping its interaction with the patient. Moreover, information is sent to a cloud, so that robot moods, states and interactions can be shared among different robots. Conclusions: Pleo attachment was successful for more than 1 month, working with children in therapy, which makes the investment capable of positive therapeutic possibilities. This technical improvement in the Pleo addresses two key issues in social robotics: needing an enhanced response to maintain the attention and engagement of the child, and using the system as a platform to collect the states of the child’s progress for clinical purposes.Peer ReviewedPostprint (published version

Building a software service for mobile devices to enhance awareness in web collaboration

(c) 2014 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.In this paper, we propose the construction of an effective event notification software service for mobile devices to provide anytime anywhere awareness to online work teams during Web collaboration. The software service is first designed to achieve the required flexibility to be used in different collaborative work situations, from professional work to informal communities of practice. Then, the building of our event-oriented service for mobile clients is reported from all the stages of our software engineering methodology and it is prototyped for evaluation purposes. We believe the outcomes of our approach will be very beneficial for achieving more productive and quality Web collaboration practices. The ultimate aim of this research is to provide software designers of Web collaboration tools and applications with general guidelines as for how to face common issues and challenges when incorporating a complete event management and notification system in their developments.Peer ReviewedPostprint (author's final draft

Efectividad de un programa grupal psicoeducativo para la depresión mayor en atención primaria: ensayo clínico controlado aleatorizado

Sin resumen

Parkinson’s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration

A deeper understanding of early disease mechanisms occurring in Parkinson's disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients' networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases

Activity and high-order effective connectivity alterations in Sanfilippo C patient-specific neuronal networks

Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration

Engineered Macroscale Cardiac Constructs Elicit Human Myocardial Tissue-like Functionality

In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term "CardioSlice." PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients

The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and a transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic PD (sPD), and healthy subjects. We observed extensive DNA methylation changes in PD DAn, and of RNA expression, which were common in L2PD and sPD. No significant methylation differences were present in parental skin cells, undifferentiated iPSCs nor iPSC-derived neural cultures not-enriched-in-DAn. These findings suggest the presence of molecular defects in PD somatic cells which manifest only upon differentiation into the DAn cells targeted in PD. The methylation profile from PD DAn, but not from controls, resembled that of neural cultures not-enriched-in-DAn indicating a failure to fully acquire the epigenetic identity own to healthy DAn in PD. The PD-associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the RNA and/or protein downregulation of a network of transcription factors relevant to PD (FOXA1, NR3C1, HNF4A, and FOSL2). Using a patient-specific iPSC-based DAn model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD

Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy

Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA. Keywords: age-related macular degeneration (AMD); geographic atrophy; pig; animal model; stem cells; iPSC; RPE; retina; regenerative medicine; advanced cell therap