NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin.

Engaging patients and parents to improve mental health intervention for youth with rheumatological disease.

BACKGROUND: Mental health disorders are common in youth with rheumatological disease yet optimal intervention strategies are understudied in this population. We examined patient and parent perspectives on mental health intervention for youth with rheumatological disease. METHODS: We conducted a mixed methods cross-sectional study, via anonymous online survey, developed by researchers together with patient/parent partners, to quantitatively and qualitatively examine youth experiences with mental health services and resources in North America. Patients ages 14-24 years with juvenile idiopathic arthritis, juvenile dermatomyositis, or systemic lupus erythematous, and parents of patients ages 8-24 with these diseases were eligible (not required to participate in pairs). Participants self-reported mental health problems (categorized into clinician-diagnosed disorders vs self-diagnosed symptoms) and treatments (e.g. therapy, medications) received for the youth. Multivariate linear regression models compared patient and parent mean Likert ratings for level of: i) comfort with mental health providers, and ii) barriers to seeking mental health services, adjusting for potential confounders (patient age, gender, disease duration, and patient/parent visual analog score for disease-related health). Participants indicated usefulness of mental health resources; text responses describing these experiences were analyzed by qualitative description. RESULTS: Participants included 123 patients and 324 parents. Patients reported clinician-diagnosed anxiety (39%) and depression (35%); another 27 and 18% endorsed self-diagnosed symptoms of these disorders, respectively. 80% of patients with clinician-diagnosed disorders reported receiving treatment, while 11% of those with self-diagnosed symptoms reported any treatment. Patients were less comfortable than parents with all mental health providers. The top two barriers to treatment for patients and parents were concerns about mental health providers not understanding the rheumatological disease, and inadequate insurance coverage. Over 60% had used patient mental health resources, and over 60% of these participants found them to be helpful, although text responses identified a desire for resources tailored to patients with rheumatological disease. CONCLUSION: Self-reported mental health problems are prevalent for youth in this sample with rheumatological disease, and obstacles to mental health treatment include disease-related and logistic factors. Strategies are needed to improve acceptance and accessibility of mental health intervention, including routine mental health screening and availability of disease-specific mental health resources.

Identifying Research Priorities among Patients and Families of Children with Rheumatic Diseases Living in the United States.

OBJECTIVE: To improve the quality and participation in pediatric rheumatology research, patient-prioritized studies should be emphasized. We collaborated with United States-based pediatric rheumatology advocacy organizations to survey patients and caregivers of children with rheumatic diseases to identify what research topics were most important to them. METHODS: We conducted Web-based surveys and focus groups (FG) of patients and caregivers of children with juvenile myositis (JM), juvenile arthritis (JA), and childhood-onset systemic lupus erythematosus (cSLE). Surveys were emailed to listservs and posted to social media sites of JM, JA, and cSLE patient advocacy organizations. An initial survey asked open-ended questions about patient/caregiver research preferences. Responses were further characterized through FG. A final ranking survey asked respondents to rank from a list of research themes the 7 most important to them. RESULTS: There were 365 JM respondents, 44 JA respondents, and 32 cSLE respondents to the final ranking survey. The top research priority for JM was finding new treatments, and for JA and cSLE, the priority was understanding genetic/environmental etiology. The 3 prioritized research themes common across all disease groups were medication side effects, disease flare, and disease etiology. CONCLUSION: Patient-centered research prioritization is recognized as valuable in conducting high-quality research, yet there is a paucity of data describing patient/family preferences, especially in pediatrics. We used multimodal methodologies to assess current patient/caregiver research priorities to help frame the agenda for the pediatric rheumatology research community. Patients and caregivers from all surveyed disease groups prioritized the study of medication side effects, disease flares, and disease etiology.