Probing single ventricle heart defects with patient-derived induced pluripotent stem cells and emerging technologies.

Single ventricle heart defects (SVHDs) are a severe type of congenital heart disease with poorly understood pathogenic mechanisms. New research using patient-specific induced pluripotent stem cells (iPSCs) as a cellular model is beginning to uncover genetic and cellular etiologies of SVHDs. Hypoplastic left heart syndrome (HLHS) is a type of SVHD that is characterized by an underdeveloped left ventricle and other malformations in the left side of the heart. Hypoplastic right heart syndrome (HRHS), the second type of SVHD, is characterized by an underdeveloped right heart, including malformed tricuspid and pulmonary valves. Despite a noticeable lack of research on SVHD, emerging technologies offer a promising future to further probe the genetic and cellular mechanisms of these diseases. Pediatric cardiovascular research is at the dawn of a new era in terms of what can be discovered with patient-specific iPSCs in conjunction with other technologies (e.g., organoids, single-cell genomics, CRISPR/Cas9 genome editing). In this review, we present recent approaches and findings utilizing patient-specific iPSCs to identify cellular mechanisms responsible for improper cardiac organogenesis in HLHS and HRHS.

ChanFAD: A Functional Annotation Database for Ion Channels.

Ion channels are integral membrane protein complexes critical for regulation of membrane potential, cell volume, and other signaling events. As complex molecular assemblies with many interacting partners, ion channels have multiple structural and functional domains. While channel sequence and functional data are readily available across multiple online resources, there is an unmet need for functional annotation directly relating primary sequence information, 2D interactions, and three-dimensional protein structure. To this end, we present ChanFAD (Channel Functional Annotation Database), to provide the research community with a centralized resource for ion channel structure and functional data. ChanFAD provides functional annotation of PDB structures built on the National Center for Biotechnology Information's iCn3D structure viewing tool while providing additional information such as primary sequence, organism, and relevant links to other databases. Here we provide a brief tour of ChanFAD functionality while showing example use cases involving drug-channel interactions and structural changes based on mutation. ChanFAD is freely available and can be accessed at https://www.chanfad.org/.

Parent participation in the neonatal intensive care unit: Predictors and relationships to neurobehavior and developmental outcomes.

OBJECTIVE: To 1) define predictors of parent presence, any holding, holding in arms, and skin-to-skin care in the NICU and 2) investigate the relationships between parent participation and a) early neurobehavior and b) developmental outcomes at age 4 to 5years among preterm infants. METHODS: Eighty-one preterm infants born ≤32weeks estimated gestational age were prospectively enrolled within one week of life in a level III-IV NICU. Parent (maternal and paternal) presence and holding (including holding in arms and skin-to-skin care) were tracked throughout NICU hospitalization. Neurobehavior at term equivalent age and development at 4 to 5years were determined using standardized assessments. RESULTS: The median number of days per week parents were documented to be present over NICU hospitalization was 4.0 (IQR=2.4-5.8) days; days held per week 2.8 (IQR=1.4-4.3) days [holding in arms days per week was 2.2 (IQR=1.2-3.2) days and parent skin-to-skin care days per week was 0.2 (IQR=0.0-0.7) days]. More parent presence was observed among mothers who were Caucasian, married, older, or employed and among those who had fewer children, familial support and provided breast milk (p<0.05). More holding was observed in infants with fewer medical interventions (p<0.05) and among those who were Caucasian, had a father who was employed, had fewer children and family support (p<0.05). More parent holding in the NICU was related to better reflex development at term age (p=0.02). More parent skin-to-skin care was related to better infant reflexes (p=0.03) and less asymmetry (p=0.04) at term and better gross motor development (p=0.02) at 4-5years. DISCUSSION: Social and medical factors appear to impact parent presence, holding, and skin-to-skin care in the NICU. Parent holding is related to better developmental outcomes, which highlights the importance of engaging families in the NICU.