Using co-design to develop a tool for shared goal-setting with parents in speech and language therapy.

BACKGROUND: Despite the compelling case for engaging parents in speech and language therapy, research indicates that speech and language therapists (SLTs) currently have a leading role in the goal-setting process of therapy for children with developmental language disorder (DLD). Therefore, we set out to develop a tool that aims to support the dialogue between SLTs and parents and enhance shared decision-making about children's communicative participation goals. We used co-design techniques with SLT-practitioners to include their perspectives throughout the design process. Although co-design has been used for some years in healthcare research, it is still a relatively new research methodology in the field of speech and language therapy. AIMS: To provide a detailed description of the co-design process that led to the development of a physical artefact that can support SLTs to engage parents of children with DLD in collaborative goal-setting. METHODS & PROCEDURES: The Design Council's Double Diamond model was used to develop a tool in co-design, together with eight SLTs, who participated in all stages of the development process. Usability was tested in actual goal-setting conversations between four SLTs and 11 parents of a child with DLD resulting in stepwise improvements. In addition, usability of the first and final prototypes was tested with five usability criteria that were rated on a 10-point scale by 64 SLTs. OUTCOMES & RESULTS: The co-design process resulted in the development of a physical prototype of the tool called 'ENGAGE', consisting of a metal 'tree trunk' on which parents can stick magnetic 'leaves' containing potential participation goals for their child. The 'tree' shape represents a child's development and opportunities for growth. This first prototype received marks between 7.0 and 8.0 out of 10 on attractiveness, user-friendliness, safety, functionality and affordability. After several iterations, there were significantly higher marks for attractiveness, user-friendliness and safety in favour for the final prototype. Marks for functionality and affordability did not change significantly. CONCLUSIONS & IMPLICATIONS: As researchers we usually develop pen-and-paper tools, interview protocols, apps or questionnaires to support clinical practice. Including the SLTs' perspectives in the design process resulted in a tree-shaped physical artefact that, according to the SLTs, helps to order information and encourages and guides their dialogue with parents. We strongly advocate the inclusion of end-users in developing innovative user-centred tools for speech and language therapy and we hope that this will become widespread practice. WHAT THIS PAPER ADDS: What is already known on the subject Collaborative goal-setting is at the heart of family-centred speech and language therapy. However, research indicates that goal-setting processes for children with DLD are currently predominantly therapist-led, instead of family-centred. Reasons for the lack of parental engagement are that effective communication with parents throughout the goal-setting process appears to be complex, and parents are not always invited and supported to engage in this. We used co-design to develop a tool that aims to support SLTs in their dialogue about therapy goals with parents. What this paper adds to existing knowledge This paper provides an example of applying a co-design approach for the development of a shared goal-setting tool for SLTs and parents of young children with DLD. The co-design approach enabled us to incorporate needs, experiences and ideas of SLTs in the design process. We report the four stages in the co-design process from (1) discovering the needs, wants and desires of the people involved, (2) defining the problem that SLTs experience, (3) developing several solutions and selecting the best solution, and (4) developing and testing the prototype. The detailed description of this process can add to an understanding of the advantages and disadvantages of a design process that includes the perspective of end-users. The result is a physical artefact representing a tree, which aims to support the conversation between SLTs and parents about a child's communicative participation. Items describing facets of communicative participation are printed on 'leaves' that can be hung on a tree trunk by parents. The tree shape is a positive metaphor for the growth and development of a child. What are the potential or actual clinical implications of this work? This study describes how SLTs can be meaningfully involved as partners in a co-design research approach. Incorporating experience from clinical practice was highly relevant since our study aimed to create a solution that would support goal-setting and service delivery by SLTs. We want to show that it is inspiring and beneficial for SLTs to partner with researchers in innovation of their own clinical practice and provide examples of co-design activities that illustrate the involvement and influence of end-users in a design process. Including the perspective of SLTs in the development of a new tool to facilitate the dialogue between SLTs and parents of children with DLD regarding therapy goal-setting is expected to add value and enhance its implementation in clinical practice.

Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition.

Autophagy has emerged as a key cellular process for organellar quality control, yet this pathway apparently fails to eliminate mitochondria containing pathogenic mutations in mitochondrial DNA (mtDNA) in patients with a variety of human diseases. In order to explore how mtDNA-mediated mitochondrial dysfunction interacts with endogenous autophagic pathways, we examined autophagic status in a panel of human cytoplasmic hybrid (cybrid) cell lines carrying a variety of pathogenic mtDNA mutations. We found that both genetic- and chemically induced loss of mitochondrial transmembrane potential (Δψ(m)) caused recruitment of the pro-mitophagic factor Parkin to mitochondria. Strikingly, however, the loss of Δψ(m) alone was insufficient to prompt delivery of mitochondria to the autophagosome (mitophagy). We found that mitophagy could be induced following treatment with the mTORC1 inhibitor rapamycin in cybrids carrying either large-scale partial deletions of mtDNA or complete depletion of mtDNA. Further, we found that the level of endogenous Parkin is a crucial determinant of mitophagy. These results suggest a two-hit model, in which the synergistic induction of both (i) mitochondrial recruitment of Parkin following the loss of Δψ(m) and (ii) mTORC1-controlled general macroautophagy is required for mitophagy. It appears that mitophagy can be accomplished by the endogenous autophagic machinery, but requires the full engagement of both of these pathways.

Mitophagy and Parkinson's disease: be eaten to stay healthy.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders. Pathologically, it is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Although most occurrences have an unknown cause, several gene mutations have been linked to familial forms of PD. The discovery of some of the proteins encoded by these genes, including Parkin, PINK1 and DJ-1, at the mitochondria offered a new perspective on the involvement of mitochondria in PD. Specifically, these proteins are thought to be involved in the maintenance of a healthy pool of mitochondria by regulating their turnover by mitochondrial autophagy, or mitophagy. In this review, we discuss recent studies on the role of mitophagy in PD. We present three putative models whereby PINK1 and Parkin may affect mitophagy; 1) by shifting the balance between fusion and fission of the mitochondrial network, 2) by modulating mitochondrial motility and 3) by directly recruiting the autophagic machinery to damaged mitochondria. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

PINK1-dependent recruitment of Parkin to mitochondria in mitophagy.

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of DeltaPsi(m) relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal DeltaPsi(m). We also show that once at the mitochondria, Parkin is in close proximity to PINK1, but we find no evidence that Parkin catalyzes PINK1 ubiquitination or that PINK1 phosphorylates Parkin. However, co-overexpression of Parkin and PINK1 collapses the normal tubular mitochondrial network into mitochondrial aggregates and/or large perinuclear clusters, many of which are surrounded by autophagic vacuoles. Our results suggest that Parkin, together with PINK1, modulates mitochondrial trafficking, especially to the perinuclear region, a subcellular area associated with autophagy. Thus by impairing this process, mutations in either Parkin or PINK1 may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease.

Mitophagy in cells with mtDNA mutations: being sick is not enough.

Despite the emergence of autophagy as a key process for mitochondrial quality control, the existence and persistence of pathogenic mtDNA mutations in human disease suggests that the degradation of dysfunctional mitochondria does not occur widely in vivo. During macroautophagy, a double-membraned cup-shaped structure engulfs cytosolic content. This autophagic vesicle then fuses with lysosomes, allowing hydrolytic enzymes to degrade the contents. Mitochondrial autophagy, or mitophagy, is thought to degrade damaged or nonfunctioning mitochondria specifically. The Parkinson disease-related proteins PINK1 (a mitochondrially localized kinase) and PARK2 (PARKIN, a cytosolically-localized E3 ubiquitin ligase) are essential for targeting mitochondria for mitophagy. Upon chemical uncoupling of the mitochondrial transmembrane potential (Δψ(m)), PINK1 located in the mitochondrial outer membrane recruits PARK2 from the cytosol to the mitochondria, followed by delivery of the organelle to the autophagic machinery for degradation.

Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease.

Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Alterations in macroautophagy, the main process responsible for bulk autophagic degradation, have been proposed to contribute to pathogenesis in Huntington's disease (HD), a genetic neurodegenerative disorder caused by an expanded polyglutamine tract in the huntingtin protein. However, the precise mechanism behind macroautophagy malfunction in HD is poorly understood. In this work, using cellular and mouse models of HD and cells from humans with HD, we have identified a primary defect in the ability of autophagic vacuoles to recognize cytosolic cargo in HD cells. Autophagic vacuoles form at normal or even enhanced rates in HD cells and are adequately eliminated by lysosomes, but they fail to efficiently trap cytosolic cargo in their lumen. We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells.

Is there a pathogenic role for mitochondria in Parkinson's disease?

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause. For decades, a deficit in mitochondrial respiration was thought to be a key factor in PD neurodegeneration. However, excluding a few exceptions where a clinical picture of parkinsonism is associated with a mitochondrial DNA mutation, preclinical and clinical studies have failed to identify any genetic mutations in the genes encoding for the electron transport chain complexes in PD patients. More recently, it has been discovered that mutations in the genes encoding for Parkin, PINK1 and DJ1 are associated with familial forms of PD and with mitochondrial alterations, including morphological abnormalities. These results have led many researchers to revisit the question of mitochondrial biology as a primary mechanism in PD pathogenesis, this time from an angle of perturbation in mitochondrial dynamics and not from the angle of a deficit in respiration.