We used patient dermal fibroblasts to characterize the mitochondrial abnormalities associated with the dilated cardiomyopathy with ataxia syndrome (DCMA) and to study the effect of the mitochondrially-targeted peptide SS-31 as a potential novel therapeutic. DCMA is a rare and understudied autosomal recessive disorder thought to be related to Barth syndrome but caused by mutations in DNAJC19, a protein of unknown function localized to the mitochondria. The clinical disease is characterized by 3-methylglutaconic aciduria, dilated cardiomyopathy, abnormal neurological development, and other heterogeneous features. Until recently no effective therapies had been identified and affected patients frequently died in early childhood from intractable heart failure. Skin fibroblasts from four pediatric patients with DCMA were used to establish parameters of mitochondrial dysfunction. Mitochondrial structure, reactive oxygen species (ROS) production, cardiolipin composition, and gene expression were evaluated. Immunocytochemistry with semi-automated quantification of mitochondrial structural metrics and transmission electron microscopy demonstrated mitochondria to be highly fragmented in DCMA fibroblasts compared to healthy control cells. Live-cell imaging demonstrated significantly increased ROS production in patient cells. These abnormalities were reversed by treating DCMA fibroblasts with SS-31, a synthetic peptide that localizes to the inner mitochondrial membrane. Levels of cardiolipin were not significantly different between control and DCMA cells and were unaffected by SS-31 treatment. Our results demonstrate the abnormal mitochondria in fibroblasts from patients with DCMA and suggest that SS-31 may represent a potential therapy for this devastating disease.
Pediatric primary care practices would benefit from assessing their organizational context and taking steps to address it prior to or in a phased approach with mental health service implementation.
A variety of interventions at the patient-provider, clinical site, system, and policy levels can foster relationships and provide the foundation for care capable of addressing promotion of social and emotional well-being in general and trauma prevention and treatment in particular.
Mental health concerns are common in pediatric primary care, but practitioners report low levels of comfort managing them. A primary care intervention addressing organizational and individual factors was developed to improve the management of common mental health conditions.
Mindfulness-based stress reduction (MBSR) has been shown to improve health outcomes across populations. We explored the feasibility, acceptability, and initial effects of a pilot MBSR program at a highly-ranked university in the United States. We conducted 23 in-depth interviews with 13 students. Interviews explored stressors and coping mechanisms, experiences with MBSR, and its reported impact and potential future use. Interviews were analyzed using thematic content and narrative analyses. Results indicated that students are exposed to a very high level of constant stress related to the sheer amount of work and activities that they have and the pervasive surrounding university culture of perfectionism. MBSR offered an opportunity to step back and gain perspective on issues of balance and priorities and provided concrete techniques to counter the effects of stressors. We conclude that MBSR and mindfulness programs may contribute to more supportive university learning environments and greater health and well-being among students.
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