SUNY Upstate Medical University

To assess factors associated with retinal detachment (RD) in eyes presenting with endogenous endophthalmitis (EE). Multicenter retrospective study of individuals with an EE diagnosis from seven tertiary care centers. Demographics, medical history, ocular examination findings, microbial cultures (blood or intraocular), and management strategies were assessed relative to subsequent RD occurring within 6 months of EE diagnosis. Of note, this study did not distinguish between intraocular cultures without growth and eyes that were not sampled for an intraocular organism. A total of 201 eyes from 171 patients presented with EE. Of these, 22.4% (45/201) had a subsequent RD. Eyes that experienced a subsequent RD had worse presenting visual acuity ( P = 0.006) and lower intraocular pressure at presentation (RD: 13.7 ± 5.4 mmHg vs. No RD: 15.7 ± 6.5 mmHg, P = 0.04). Compared with other forms of bacteremia, S. aureus bacteremia was associated with increased odds of subsequent RD (OR: 6.10, CI: 1.82-20.41, P = 0.003). Eyes with a subsequent RD did not have significantly greater rates of therapeutic pars plana vitrectomy (RD: 11/48, 22.9% vs. No RD: 36/153, 23.5%). Eyes presenting with visual acuity ≤ light perception or S. aureus bacteremia had a higher risk of subsequent RD and may warrant closer surveillance. Although no therapeutic strategies were associated with reduced odds of subsequent RD, a pars plana vitrectomy was not associated with an increased risk of RD, suggesting that it may aid in eyes with lackluster responses to systemic and intravitreal pharmacotherapy.

The human heart, originating from the splanchnic mesoderm, is the first functional organ to develop, co-evolving with the foregut endoderm through reciprocal signaling. Previously, cardioid models offered new insights on cardiovascular cell lineages and tissue morphogenesis during heart development, while mesoderm-endoderm crosstalk remain incompletely understood. Here, we integrated micropatterned cardioids, CRISPR-engineered reporter hiPSCs, deep-tissue imaging, and single-cell RNA sequencing (scRNA-seq) to explore synergistic mesoderm-endoderm co-development. scRNA-seq with PHATE trajectory mapping reconstructed lineage bifurcations of mesoderm-heart and endoderm-foregut lineages, identifying key cell types in cardiac and hepatic development. Ligand-receptor interaction analysis highlighted mesodermal cells enriched in non-canonical WNT, NRG, and TGF-β signaling, while endodermal cells exhibited VEGF and Hedgehog activity. We found that micropattern sizes influenced cellular composition, cardioid cavitation, contractile functions, and mesoderm-endoderm signaling crosstalk. The cardioids generated from 600µm diameter circle patterns showed larger cavity formation resembling early heart chamber formation. Our findings establish micropatterned cardioids as a model for mesoderm-endoderm co-development, enhancing our understanding of heart-foregut synergy during early embryogenesis.

Loss of Med12 and Med13 causes dedifferentiation of intermediate neural progenitorsMed12 and Med13 mediate the activation of target genes of PntP1Loss of Med12 and Med13 leads to premature loss of neural stem cellsMed12 and Med13 act with one subset of core mediator subunits but oppose another. Zhu and his colleagues show that Med12 and Med13 promote cell fate commitment of intermediate neural progenitor cells and self-renewal of neural stem cells. Med12 and Med13 perform these two distinct functions by coordinating with one subset of core mediator complex subunits while opposing another to regulate the expression of different target genes.