Hospital EHR adoption is widespread and many hospitals are using EHRs to support performance measurement and patient engagement. However, this is not happening across all hospitals.
The developmental activities of morphogens are controlled by the gradients that they form in the extracellular matrix (ECM). In this report, we show that differences in the binding of fibroblast growth factor 7 (FGF7) and FGF10 to heparan sulfate (HS) underlie the formation of different gradients that dictate distinct activities during branching morphogenesis. Reducing the binding affinity of FGF10 for HS by mutating a single residue in its HS-binding pocket converted FGF10 into a functional mimic of FGF7 with respect to gradient formation and regulation of branching morphogenesis; in particular by causing lacrimal and salivary gland epithelium to branch rather than elongate. In contrast, mutations that reduced the affinity of the FGF10 for its receptor affected the extent, but not the nature, of the response. Our data may provide a general model for understanding how binding to HS regulates other morphogenetic gradients.
The United States is making substantial investments to accelerate the adoption and use of interoperable electronic health record (EHR) systems. Using data from the 2009-13 Electronic Health Records Survey, we found that EHR adoption continues to grow: In 2013, 78 percent of office-based physicians had adopted some type of EHR, and 48 percent had the capabilities required for a basic EHR system. However, we also found persistent gaps in EHR adoption, with physicians in solo practices and non-primary care specialties lagging behind others. Physicians' electronic health information exchange with other providers was limited, with only 14 percent sharing data with providers outside their organization. Finally, we found that 30 percent of physicians routinely used capabilities for secure messaging with patients, and 24 percent routinely provided patients with the ability to view online, download, or transmit their health record. These findings suggest that although EHR adoption continues to grow, policies to support health information exchange and patient engagement will require ongoing attention.A ccelerating the adoption of health information technology (IT) has been recognized as a national policy priority for more than a decade. HITECH's goals are to promote the adoption and use of interoperable electronic health records (EHRs) and health information exchange (HIE), which can serve as the foundation for improvements in the cost and quality of the US health care delivery system. 3 In particular, modernizing the country's health IT infrastructure enables broader efforts to pursue new models of care delivery. To help move the country toward this goal, beginning in 2011 the Centers for Medicare and Medicaid Services (CMS) began making incentive payments to eligible professionals who demonstrated the regular use of specific computerized capabilities that meet meaningful-use objectives.
4Early evidence on the impact of HITECH suggested that its investments had accelerated the rate of EHR adoption. From 2010 to 2012 adoption of basic EHR systems and specific meaningful-use capabilities grew rapidly among US ambulatory care physicians.
5Physicians who previously had significantly lower rates of adoption, 6 including those who were older or worked in rural areas or areas with high rates of poverty, had the highest relative gains.
Physicians reported EHR use enhanced patient care overall. Clinical benefits were most likely to be reported by physicians using EHRs meeting Meaningful Use criteria and longer EHR experience.
Laminin alpha chains have unique spatiotemporal expression patterns during development and defining their function is necessary to understand the regulation of epithelial morphogenesis. We investigated the function of laminin alpha5 in mouse submandibular glands (SMGs). Lama5(-/-) SMGs have a striking phenotype: epithelial clefting is delayed, although proliferation occurs; there is decreased FGFR1b and FGFR2b, but no difference in Lama1 expression; later in development, epithelial cell organization and lumen formation are disrupted. In wild-type SMGs alpha5 and alpha1 are present in epithelial clefts but as branching begins alpha5 expression increases while alpha1 decreases. Lama5 siRNA decreased branching, p42 MAPK phosphorylation, and FGFR expression, and branching was rescued by FGF10. FGFR siRNA decreased Lama5 suggesting that FGFR signaling provides positive feedback for Lama5 expression. Anti-beta1 integrin antibodies decreased FGFR and Lama5 expression, suggesting that beta1 integrin signaling provides positive feedback for Lama5 and FGFR expression. Interestingly, the Itga3(-/-):Itga6(-/-) SMGs have a similar phenotype to Lama5(-/-). Our findings suggest that laminin alpha5 controls SMG epithelial morphogenesis through beta1 integrin signaling by regulating FGFR expression, which also reciprocally regulates the expression of Lama5. These data link changes in basement membrane composition during branching morphogenesis with FGFR expression and signaling.
Radiotherapy for head and neck cancer often has undesirable effects on salivary glands that lead to xerostomia or severe dry mouth, which can increase oral infections. Our goal is to engineer functional, three‐dimensional (3D) salivary gland neotissue for autologous implantation to provide permanent relief. An immediate need exists to obtain autologous adult progenitor cells as the use of embryonic and induced pluripotent stem cells potentially pose serious risks such as teratogenicity and immunogenic rejection. Here, we report an expandable population of primary salivary human stem/progenitor cells (hS/PCs) that can be reproducibly and scalably isolated and propagated from tissue biopsies. These cells have increased expression of progenitor markers (K5, K14, MYC, ETV4, ETV5) compared with differentiation markers of the parotid gland (acinar: MIST1/BHLHA15 and AMY1A; ductal: K19 and TFCP2L1). Isolated hS/PCs grown in suspension formed primary and secondary spheres and could be maintained in long‐term 3D hydrogel culture. When grown in a customized 3D modular hyaluronate‐based hydrogel system modified with bioactive basement membrane‐derived peptides, levels of progenitor markers, indices of proliferation, and viability of hS/PCs were enhanced. When appropriate microenvironmental cues were provided in a controlled manner in 3D, such as stimulation with β‐adrenergic and cholinergic agonists, hS/PCs differentiated into an acinar‐like lineage, needed for saliva production. We conclude that the stem/progenitor potential of adult hS/PCs isolated without antigenic sorting or clonal expansion in suspension, combined with their ability to differentiate into specialized salivary cell lineages in a human‐compatible culture system, makes them ideal for use in 3D bioengineered salivary gland applications. Stem Cells Translational Medicine
2017;6:110–120
The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review will focus on research on mouse submandibular gland development and the translation of this basic research towards therapy for patients suffering from salivary hypofunction. Here we review the most recent literature that has enabled a better understanding of the mechanisms of salivary gland development. Additionally, we discuss approaches proposed to restore salivary function using gene and cell-based therapy. Increasing our understanding of the developmental mechanisms involved during development is critical to design effective therapies for regeneration and repair of damaged glands.
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