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Background: This project aimed to optimize communication strategies to support family communication about familial hypercholesterolemia (FH) and improve cascade testing uptake among at-risk relatives. Individuals and families with FH provided feedback on multiple strategies including: a family letter, digital tools, and direct contact., Methods: Feedback from participants was collected via dyadic interviews (n = 11) and surveys (n = 98) on communication strategies and their proposed implementation to improve cascade testing uptake. We conducted a thematic analysis to identify how to optimize each strategy. We categorized optimizations and their implementation within the project's healthcare system using a Traffic Light approach., Results: Thematic analysis resulted in four distinct suggested optimizations for each communication strategy and seven suggested optimizations that were suitable across all strategies. Four suggestions for developing a comprehensive cascade testing program, which would offer all optimized communication strategies also emerged. All optimized suggestions coded green (n = 21) were incorporated. Suggestions coded yellow (n = 12) were partially incorporated. Only two suggestions were coded red and could not be incorporated., Conclusions: This project demonstrates how to collect and analyze stakeholder feedback for program design. We identified feasible suggested optimizations, resulting in communication strategies that are patient-informed and patient-centered. Optimized strategies were implemented in a comprehensive cascade testing program., (© 2023. The Author(s).)

Background: This is a case report of an asymptomatic SARS-CoV-2 infection associated with new-onset nephrotic syndrome in a pediatric patient. This is the third case of new-onset nephrotic syndrome in children associated with SARS-CoV-2 infection, but is the first case report describing a new-onset nephrotic syndrome presentation in a patient who had asymptomatic COVID-19 infection., Case Presentation: This is a case of a previously healthy 5 year old female who presented with new-onset nephrotic syndrome in the setting of an asymptomatic COVID-19 infection. She presented with progressive edema, and laboratory findings were significant for proteinuria and hypercholesterolemia. She was treated with albumin, diuretics, and corticosteroid therapy, and achieved clinical remission of her nephrotic syndrome within 3 weeks of treatment. Though she was at risk of hypercoagulability due to her COVID-19 infection and nephrotic syndrome, she was not treated with anticoagulation, and did not develop any thrombotic events., Conclusions: Our case report indicates that SARS-CoV-2 infection could be a trigger for nephrotic syndrome, even in the absence of overt COVID-19 symptoms., (© 2021. The Author(s).)

Background: The homeobox transcription factor Engrailed2 (En2) has been studied extensively in neurodevelopment, particularly in the midbrain/hindbrain region and cerebellum, where it exhibits dynamic patterns of expression and regulates cell patterning and morphogenesis. Because of its roles in regulating cerebellar development and evidence of cerebellar pathology in autism spectrum disorder (ASD), we previously examined an ENGRAILED2 association and found evidence to support EN2 as a susceptibility gene, a finding replicated by several other investigators. However, its functions at the cell biological level remain undefined. In the mouse, En2 gene is expressed in granule neuron precursors (GNPs) just as they exit the cell cycle and begin to differentiate, raising the possibility that En2 may modulate these developmental processes., Methods: To define En2 functions, we examined proliferation, differentiation and signaling pathway activation in En2 knockout (KO) and wild-type (WT) GNPs in response to a variety of extracellular growth factors and following En2 cDNA overexpression in cell culture. In vivo analyses of cerebellar GNP proliferation as well as responses to insulin-like growth factor-1 (IGF1) treatment were also conducted., Results: Proliferation markers were increased in KO GNPs in vivo and in 24-h cultures, suggesting En2 normally serves to promote cell cycle exit. Significantly, IGF1 stimulated greater DNA synthesis in KO than WT cells in culture, a finding associated with markedly increased phospho-S6 kinase activation. Similarly, there was three-fold greater DNA synthesis in the KO cerebellum in response to IGF1 in vivo. On the other hand, KO GNPs exhibited reduced neurite outgrowth and differentiation. Conversely, En2 overexpression increased cell cycle exit and promoted neuronal differentiation., Conclusions: In aggregate, our observations suggest that the ASD-associated gene En2 promotes GNP cell cycle exit and differentiation, and modulates IGF1 activity during postnatal cerebellar development. Thus, genetic/epigenetic alterations of EN2 expression may impact proliferation, differentiation and IGF1 signaling as possible mechanisms that may contribute to ASD pathogenesis.

Background and Methods: Stem or progenitor cells from healthy tissues have the capacity to co-segregate their template DNA strands during mitosis. Here, we set out to test whether breast cancer cell lines also possess the ability to asymmetrically segregate their template DNA strands via non-random chromosome co-segregation, and whether this ability correlates with certain properties attributed to breast cancer stem cells (CSCs). We quantified the frequency of asymmetric segregation of template DNA strands in 12 human breast cancer cell lines, and correlated the frequency to molecular subtype, CD44+/CD24-/lo phenotype, and invasion/migration ability. We tested if co-culture with human mesenchymal stem cells, which are known to increase self-renewal, can alter the frequency of asymmetric segregation of template DNA in breast cancer., Results: We found a positive correlation between asymmetric segregation of template DNA and the breast cancer basal-like and claudin-low subtypes. There was an inverse correlation between asymmetric segregation of template DNA and Her2 expression. Breast cancer samples with evidence of asymmetric segregation of template DNA had significantly increased invasion and borderline significantly increased migration abilities. Samples with high CD44+/CD24-/lo surface expression were more likely to harbor a consistent population of cells that asymmetrically segregated its template DNA; however, symmetric self-renewal was enriched in the CD44+/CD24-/lo population. Co-culturing breast cancer cells with human mesenchymal stem cells expanded the breast CSC pool and decreased the frequency of asymmetric segregation of template DNA., Conclusions: Breast cancer cells within the basal-like subtype can asymmetrically segregate their template DNA strands through non-random chromosome segregation. The frequency of asymmetric segregation of template DNA can be modulated by external factors that influence expansion or self-renewal of CSC populations. Future studies to uncover the underlying mechanisms driving asymmetric segregation of template DNA and dictating cell fate at the time of cell division may explain how CSCs are maintained in tumors.