Use of Functional Electrical Stimulation for Functional Mobility of a Pediatric Patient with Cerebral Palsy: A Case Report

Background: Children with cerebral palsy (CP) have varying impairments of motor control and muscle tone, impacting functional mobility. One physical therapy intervention for children with limited functional mobility is utilizing functional electrical stimulation (FES) as an intervention to facilitate movement. FES cycling and FES assisted tasks are becoming more readily studied and utilized as an intervention for this population of patients. To date, there are few studies that evaluate the use of FES interventions combined with land based interventions in children with spastic quadriplegic CP. Purpose: Discuss the use of FES cycling and aided functional activities as an intervention for a pediatric patients with spastic quadriplegic CP. Intervention: During a four-week timeframe, a five-year-old boy with spastic quadriplegic CP, participated in physical therapy sessions one time per week utilizing FES cycling and FES assisted functional activities and one time per week utilizing adaptive cycling and non-FES assisted activities. The RT300 FES cycling machine was utilized, as well as the portable SAGE controller component of the RT300 for functional tasks of supine bridging, sit to stand, and static standing. Outcome Measures: Data points from the RT300 were utilized to track objective changes between each session of FES cycling. Qualitative data comparing the level of physical assistance required with each functional activity was utilized to track changes between FES and non-FES sessions each week. Discussion: FES cycling and FES assisted activities may provide feasible and well-tolerated physical activity interventions for children with spastic quadriplegic CP. A multi-modal intervention approach with FES and non-FES activities may provide variety and opportunities for motor learning in the pediatric setting

GPCR-induced YAP activation sensitizes fibroblasts to profibrotic activity of TGFβ1.

Tissue fibrosis is a pathological condition characterized by uncontrolled fibroblast activation that ultimately leads to organ failure. The TGFβ1 pathway, one of the major players in establishment of the disease phenotype, is dependent on the transcriptional co-activators YAP/TAZ. We were interested whether fibroblasts can be sensitized to TGFβ1 by activation of the GPCR/YAP/TAZ axis and whether this mechanism explains the profibrotic properties of diverse GPCR ligands. We found that LPA, S1P and thrombin cooperate in human dermal fibroblasts with TGFβ1 to induce extracellular matrix synthesis, myofibroblast marker expression and cytokine secretion. Whole genome expression profiling identified a YAP/TAZ signature behind the synergistic profibrotic effects of LPA and TGFβ1. LPA, S1P and thrombin stimulation led to activation of the Rho-YAP axis, an increase of nuclear YAP-Smad2 complexes and enhanced expression of profibrotic YAP/Smad2-target genes. More generally, dermal, cardiac and lung fibroblast responses to TGFβ1 could be enhanced by increasing YAP nuclear levels (with GPCR ligands LPA, S1P, thrombin or Rho activator) and inhibited by decreasing nuclear YAP (with Rho inhibitor, forskolin, latrunculin B or 2-deoxy-glucose). Thus, we present here a conceptually interesting finding that fibroblast responses to TGFβ1 can be predicted based on the nuclear levels of YAP and modulated by stimuli/treatments that change YAP nuclear levels. Our study contributes to better understanding of fibrosis as a complex interplay of signalling pathways and proposes YAP/TAZ as promising targets in the treatment of fibrosis