ABSTRACT
Youth living in poverty are more likely to experience cumulative stressors including multiple adverse childhood events. Further, the Covid-19 pandemic has disproportionality affected Hispanic youth and communities, leading to unprecedented levels of trauma. This research responded to a need for a youth resiliency-building program in an urban and impoverished area with a majority Hispanic population. We conducted a formative evaluation of a youth intervention entitled Mind Matters: Overcoming Adversity and Building Resilience, which aims to help youth overcome adversity and to build resilience via psychoeducation and skill development. Just prior to the pandemic in the United States (August-December, 2019), youth (N=12) participated in Mind Matters as part of an after-school program. Immediately following, we utilized focus groups to solicit youth's perspectives on the acceptability of the program, what they had learned, content areas they liked best, and their recommendations for program improvement. Follow-up phone interviews were also conducted three months later (March 2020) while youth were at home as a result of the pandemic. Youth enjoyed the program and were able to apply skills learned to cope with stress in their daily lives and across ecological contexts. Findings point to the program as particularly well-suited to older adolescents. During the pandemic, most youth continued to utilize self-soothing and mindfulness skills to emotionally self-regulate while facing challenges related to home schooling. Findings highlight the importance of trauma-resiliency programming for youth and offer recommendations to practitioners utilizing the Mind Matters program.
ABSTRACT
Cerebral arteriovenous malformations (AVMs) are the most common vascular malformations worldwide and the leading cause of hemorrhagic strokes that may result in crippling neurological deficits. Here, using newly generated mouse models, we uncovered that cerebral endothelial cells (ECs) acquired mesenchymal markers and caused vascular malformations. Interestingly, we found that limiting endothelial histone deacetylase 2 (HDAC2) prevented cerebral ECs from undergoing mesenchymal differentiation and reduced cerebral AVMs. We found that endothelial expression of HDAC2 and enhancer of zeste homolog 1 (EZH1) was altered in cerebral AVMs. These alterations changed the abundance of H4K8ac and H3K27me in the genes regulating endothelial and mesenchymal differentiation, which caused the ECs to acquire mesenchymal characteristics and form AVMs. Together, this investigation demonstrated that the induction of HDAC2 altered specific histone modifications, which resulted in mesenchymal characteristics in the ECs and cerebral AVMs. The results provided insight into the epigenetic impact on AVMs.
ABSTRACT
Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.
