'There's no straight line ' a consumer-informed intervention for FTD family care partners: the STELLA-FTD pilot study.

OBJECTIVES: Behavioral symptoms and communication challenges are particularly apparent in frontotemporal degenerative (FTD) dementias. There is a paucity of psychoeducation programming specifically tailored to the needs of families with FTD. We revised an existing intervention to meet the needs of these families. METHODS: We used a quasi-experimental approach. In Phase 1, we sought consumer input about an existing intervention. In Phase 2, we modified the intervention based on the qualitative findings from Phase 1 and tested the revised intervention (STELLA-FTD) for feasibility, acceptability and early-stage efficacy. Outcome for Phase 2 included feasibility data and care partner reactivity to upsetting behaviors. Secondary outcomes included data from unobtrusive sleep monitoring. An inductive analysis of transcripts from the Phase 2 STELLA-FTD focus group provides guidance for future revisions. RESULTS: Fifteen family care partners participated in the Phase 1 focus groups; sixteen care partners enrolled in Phase 2. Testing in Phase 2 revealed that the care partners found our consumer-informed revised intervention both feasible and acceptable. The post-intervention findings suggest STELLA-FTD has the potential to reduce care partner reactivity to upsetting behaviors and to decrease care partner burden. Sleep did not change over the 8-week intervention. CONCLUSIONS: The revised STELLA-FTD intervention was found to be feasible and acceptable, and has potential to improve care partner burden for families living with FTD. Providing the intervention via telehealth maximized access and engaged rehabilitation specialists in providing disease management content. Future revisions will include examination of efficacy and mechanism of action (OHSU IRB # 00022721, ClinicalTrials.gov NCT05338710).

Genetic analysis of yeast Sec24p mutants suggests cargo binding is not co-operative during ER export.

Many eukaryotic secretory proteins are selected for export from the endoplasmic reticulum (ER) through their interaction with the Sec24p subunit of the coat protein II (COPII) coat. Three distinct cargo-binding sites on yeast Sec24p have been described by biochemical, genetic and structural studies. Each site recognizes a limited set of peptide motifs or a folded structural domain, however, the breadth of cargo recognized by a given site and the dynamics of cargo engagement remain poorly understood. We aimed to gain further insight into the broader molecular function of one of these cargo-binding sites using a non-biased genetic approach. We exploited the in vivo lethality associated with mutation of the Sec24p B-site to identify genes that suppress this phenotype when overexpressed. We identified SMY2 as a general suppressor that rescued multiple defects in Sec24p, and SEC22 as a specific suppressor of two adjacent cargo-binding sites, raising the possibility of allosteric regulation of these domains. We generated a novel set of mutations in Sec24p that distinguish these two sites and examined the ability of Sec22p to rescue these mutations. Our findings suggest that co-operativity does not influence cargo capture at these sites, and that Sec22p rescue occurs via its function as a retrograde SNARE.