Cultural adaptation of the 4Rs and 2Ss multiple family group therapy for adolescents living with HIV and their families in Ghana: a systematic community-based participatory study.

Down syndrome (DS) is caused by the partial or complete trisomy of human chromosome 21 (Hsa21). This leads to a myriad of phenotypes affecting the genome, proteome, cell physiology, organ systems, and neurobehavioral repertoire of persons with DS (A). A major challenge in DS research lies in defining the pathophysiological consequences of an increased number of protein-coding and non-coding genes on Hsa21, their effects on genome-wide gene expression, and how these changes contribute to clinical manifestations. Studies using human post-mortem brain tissue and advanced systems have provided valuable insights into the molecular and cellular complexity of DS. However, these platforms have inherent limitations, particularly in their ability to model biology across tissue-types and organ-systems. Importantly, these platforms cannot model the atypical neurobehavior associated with complex developmental brain conditions. Thus, understanding the complexity of pathophysiological processes in DS, and parsing multifactorial and long-term responses to therapeutic interventions, requires a whole-organism approach. Rodent models of Down syndrome recapitulate major human phenotypes (A) Systems-level phenotypes observed in humans with Down syndrome (DS) that are captured across rodent models of DS.