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The gastrointestinal (GI) tract forms from the endoderm (which gives rise to the epithelium) and the mesoderm (which develops into the smooth muscle layer, the mesenchyme, and numerous other cell types). Much of what is known of GI development has been learned from studies of the endoderm and its derivatives, because of the importance of epithelial biology in understanding and treating human diseases. Although the necessity of epithelial-mesenchymal cross talk for GI development is uncontested, the role of the mesoderm remains comparatively less well understood. The transformation of the visceral mesoderm during development is remarkable; it differentiates from a very thin layer of cells into a complex tissue comprising smooth muscle cells, myofibroblasts, neurons, immune cells, endothelial cells, lymphatics, and extracellular matrix molecules, all contributing to the form and function of the digestive system. Understanding the molecular processes that govern the development of these cell types and elucidating their respective contribution to GI patterning could offer insight into the mechanisms that regulate cell fate decisions in the intestine, which has the unique property of rapid cell renewal for the maintenance of epithelial integrity. In reviewing evidence from both mammalian and nonmammalian models, we reveal the important role of the visceral mesoderm in the ontogeny of the GI tract. [Copyright &y& Elsevier]

Background: Bile acid (BA) reclamation following ileo-cecal resection (ICR) may prevent colonic mucosa from chronic injury. In this study, we hypothesized that in a murine model of ICR the remnant colon would upregulate the cellular machinery necessary for BA reclamation and would do so in an FXR- and bacteria-dependent manner. Methods: Conventional (WT), conventional FXR knockout (FXR null) and germ-free (GF) mice were randomized to undergo either ICR or sham operation. The ascending colon was harvested for histology and immunohistochemistry and changes in bile acid homeostatic gene expression determined by real-time polymerase chain reaction (RT-PCR) 7 days following surgery. Results: Following ICR WT mice showed significant increases in the expression of genes regulating bile acid transport including IBABP, Asbt, Ostβ and FGF 15. Increased expression of IBABP and Asbt was confirmed by immunohistochemistry. Induction of bile acid transport genes was absent or attenuated in FXR null and GF mice. Conclusion: Bacterial dependent up regulation of IBABP is FXR mediated in the colon following ICR. Mice lacking microbiota (GF) or FXR are unable to increase the expression of IBABP or FGF 15. [Copyright &y& Elsevier]

Background & Aims: Math1 (Atoh1) is a basic helix-loop-helix transcription factor important for intestinal secretory cell differentiation. We hypothesized that Math1 is important in cell fate commitment, and therefore mediates proliferative homeostasis and the adaptive response following intestinal resection in the adult intestine. Methods: We generated mice with an intestine-specific mosaic deletion of Math1 (Math1Δintestine ) using the Cre/loxP system. Histologic analysis in adult Math1Δintestine and wild-type littermates at baseline and following small bowel resection or sham surgery was performed. Results: We observed loss of Paneth, goblet, and enteroendocrine cells in Math1-null crypts. In addition, aberrant activation of the Math1 promoter occurred in absorptive enterocytes derived from Math1-null crypts, suggesting a change in cell fate. Proliferation was increased but apoptosis unchanged in Math1-mutant crypts compared to adjacent wild-type crypts. Math1Δintestine mice and wild-type littermates displayed similar physiologic adaptive responses to small bowel resection as measured by changes in body weight and ileal wet weight. In contrast, Math1-mutant crypts displayed a blunted adaptive response compared to adjacent wild-type crypts. Conclusions: We show that Math1 is essential for adult intestinal secretory cell production, and in its absence cells destined to a secretory phenotype instead adopt an absorptive phenotype. Subtle abnormalities of proliferation within Math1-null crypts in Math1Δintestine mice were identified, together with a substantial defect in the adaptive response of Math1-null crypts following small bowel resection. Our results suggest that Math1 is critical for both cell fate determination within the intestinal epithelium and for regulation of the response to intestinal resection. [Copyright &y& Elsevier]

Background & Aims: Although there have been many recent advances regarding the biology of intestinal stem cells, the field has been hampered significantly by the lack of a method to isolate these cells. Therefore, the aim of this study was to explore the hypothesis that viable intestinal stem cells can be isolated as a side population (SP) by fluorescence-activated cell sorting after staining with the DNA-binding dye Hoechst 33342. Methods: Preparations of individual cells from either whole mucosa or epithelium of mouse jejunum were stained with Hoechst 33342 and propidium iodide and then sorted using fluorescence-activated cell sorting. Cells were characterized using fluorochrome-labeled antibodies to surface markers, intracellular markers, and annexin V to detect early apoptosis. Total RNA was isolated from sorted fractions and used for quantitative real-time reverse-transcription polymerase chain reaction to evaluate the expression of cell lineage markers and the intestinal stem-cell marker, Musashi-1. Results: Adult and neonatal jejunum contain a viable population of cells that shows the SP phenotype and is sensitive to verapamil. This population of cells (from both mucosal and epithelial preparations) includes a CD45-negative fraction corresponding to nonhematopoietic cells, which shows minimal expression of surface markers typically found on stem cells from other tissues and of intracellular markers found in mesenchymal cells. Additionally, these cells were enriched for Musashi-1 and β1-integrin, were cytokeratin positive, and survived in culture for up to 14 days. Conclusions: The CD45-negative SP fraction, although not pure, represents the successful isolation of a viable population significantly enriched in small intestinal epithelial stem cells. [Copyright &y& Elsevier]

To better address physical, emotional, and social needs of Medicaid-insured pregnant women, a Federally Qualified Health Center and a hospital-based obstetrics and gynecology residency practice collaborated with their agency-based state Medicaid-sponsored home visiting program, the Maternal Infant Health Program (MIHP). In partnership, both practice sites created patient standards of care to identify and engage eligible pregnant women into underutilized home visiting services for enhanced prenatal care coordination. The purpose of this study was to describe how each practice operationalized clinical–community linkage strategies that best suited their setting and to determine if efforts resulted in improved MIHP participation and other service use. Using linked administrative data, a quasi-experimental pre–post difference-in-difference design was used to examine changes in MIHP participation, adequate prenatal care, emergency department use, and postpartum care among patients in each practice compared with the same birth cohorts between 2010 and 2015 in the rest of the state. When compared with similar women from the rest of the state, the Federally Qualified Health Center observed a 9.1 absolute percentage points (APP; 95% confidence interval [CI], 8.1–10.1) increase in MIHP participation and 12.5 APP (95% CI, 10.4–14.6) increase in early first trimester enrollment. The obstetrics and gynecology residency practice experienced increases of 4.4 APP (95% CI, 3.3–5.6) in overall MIHP participation and 12.5 APP (95% CI, 10.3–14.7) in first trimester enrollment. Significant improvements in adequate prenatal care, emergency department use, and postpartum visit completion were also observed. Clinical–community linkages can significantly improve participation of Medicaid-insured women in an evidence-based home visiting program and other prenatal services. This work is important because health providers are looking for ways to create clinical–community linkages. [ABSTRACT FROM AUTHOR]

Introduction: Enhanced prenatal/postnatal care home visiting programs for Medicaid-insured women have significant positive impacts on care and health outcomes. However, enhanced prenatal care participation rates are typically low, enrolling <30% of eligible women. This study investigates the impacts of a population-based systems approach on timely enhanced prenatal care participation and other healthcare utilization.Methods: This quasi-experimental, population-based, difference-in-differences study used linked birth certificates, Medicaid claims, and enhanced prenatal care data from complete statewide Medicaid birth cohorts (2009 to 2015), and was analyzed in 2019-2020. The population-based system intervention included cross-agency leadership and work groups, delivery system redesign with clinical-community linkages, increased enhanced prenatal care-Community Health Worker care, and patient empowerment. Outcomes included enhanced prenatal care participation and early participation, prenatal care adequacy, emergency department contact, and postpartum care.Results: Enhanced prenatal care (7.4 percentage points, 95% CI=6.3, 8.5) and first trimester enhanced prenatal care (12.4 percentage points, 95% CI=10.2, 14.5) increased among women served by practices with established clincial-community linkages, relative to that among the comparator group. First trimester enhanced prenatal care improved in the county (17.9, 95% CI=15.7, 20.0), emergency department contact decreased in the practices (-11.1, 95% CI= -12.3, -9.9), and postpartum care improved in the county (7.1, 95% CI=6.0, 8.2). Enhanced prenatal care participation for Black women served by the practices improved (4.4, 95% CI=2.2, 6.6) as well as early enhanced prenatal care (12.3, 95% CI=9.0, 15.6) and use of postpartum care (10.4, 95% CI=8.3, 12.4).Conclusions: A population systems approach improved selected enhanced prenatal care participation and service utilization for Medicaid-insured women in a county population, those in practices with established clinical-community linkages, and Black women. [ABSTRACT FROM AUTHOR]

The third postnatal week of mouse development is characterized by dramatic changes of gene expression in the small intestine. Although these changes are often assumed to reflect regulation at the level of transcription, to date there have been no direct investigations of this. In the current study we have used trehalase as a marker of intestinal maturation. Highly sensitive reverse transcriptase–polymerase chain reaction methods were developed for semi-quantitative analysis of both initial and mature transcripts, i.e., hnRNA and mRNA. Jejunums collected during normal development (specifically from postnatal days 8–21) showed parallel increases in the levels of trehalase hnRNA and mRNA. Likewise, when precocious gut maturation was elicited by dexamethasone administration on days 8–10, both initial and mature trehalase transcripts were significantly increased, although with a relatively slow time course. We conclude that both normal and glucocorticoid-induced maturation of trehalase expression reflect transcriptional activation. However, the slow time course of the glucocorticoid effect suggests that trehalase may not be a primary response gene. [Copyright &y& Elsevier]