BackgroundEpithelial-mesenchymal cross talk is centerpiece in the development of many branched organs, including the lungs. The embryonic lung mesoderm provides instructional information not only for lung architectural development, but also for patterning, commitment and differentiation of its many highly specialized cell types. The mesoderm also serves as a reservoir of progenitors for generation of differentiated mesenchymal cell types that include αSMA-expressing fibroblasts, lipofibroblasts, endothelial cells and others. Transforming Growth Factor β (TGFβ) is a key signaling pathway in epithelial-mesenchymal cross talk. Using a cre-loxP approach we have elucidated the role of the TGFβ type I receptor tyrosine kinase, ALK5, in epithelial-mesenchymal cross talk during lung morphogenesis.ResultsTargeted early inactivation of Alk5 in mesodermal progenitors caused abnormal development and maturation of the lung that included reduced physical size of the sub-mesothelial mesoderm, an established source of specific mesodermal progenitors. Abrogation of mesodermal ALK5-mediated signaling also inhibited differentiation of cell populations in the epithelial and endothelial lineages. Importantly, Alk5 mutant lungs contained a reduced number of αSMApos cells and correspondingly increased lipofibroblasts. Elucidation of the underlying mechanisms revealed that through direct and indirect modulation of target signaling pathways and transcription factors, including PDGFRα, PPARγ, PRRX1, and ZFP423, ALK5-mediated TGFβ controls a process that regulates the commitment and differentiation of αSMApos versus lipofibroblast cell populations during lung development.ConclusionALK5-mediated TGFβ signaling controls an early pathway that regulates the commitment and differentiation of αSMApos versus LIF cell lineages during lung development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0242-9) contains supplementary material, which is available to authorized users.

Nasolabial cyst (NC) or Klestadt's cyst is a relatively rare soft tissue developmental cyst occurring in the nasolabial fold, accounting for approximately 0.7% of all non-odontogenic cysts. [1][2][3] The pathogenesis of NC remains unknown, but has been attributed to epithelial remnants retained in the nasolacrimal duct extending between the lateral nasal process and maxillary prominence. [3][4][5][6] Clinically, NC presents as an asymptomatic soft swelling in the upper labial mucosa in the area of the nasolabial fold, which may cause facial asymmetry. [1][2][3][4][5][6] Pain may be experienced by patients with secondary infection due to nasal obstruction induced by the cyst. 4,5 The condition has a predilection for females, and most patients are in the fourth to fifth decades of life. NC usually appears as a solitary lesion but 10% of cases may occur bilaterally. 7 Panoramic and intraoral radiographs usually do not reveal

BACKGROUND: Evaluation of well-appearing neonates for early-onset sepsis (EOS) remains controversial. Multiple risk stratification approaches are currently used for the evaluation of EOS. Our aim was to quantify and compare frequency of laboratory evaluation and empirical antibiotics between published and local EOS approaches. METHODS: This retrospective cohort study included 8240 infants born ≥35 + 0/7 weeks’ gestation at an institution from October 1, 2014, to March 1, 2018. Excluded from analysis were 156 patients who exhibited either major congenital anomalies or required antibiotics for surgical issues. A total of 1680 patient charts with risk factors for EOS were reviewed for further demographic data, clinical presentation, laboratory results, and probable recommendations from 4 EOS risk assessment approaches. RESULTS: Laboratory evaluation recommendation was 7.1% for Centers for Disease Control and Prevention 2010 guidelines and local 2016 EOS algorithm, 6% for local 2019 EOS algorithm, and 5.9% for Kaiser Permanente neonatal EOS calculator (neonatal EOS calculator). Antibiotic recommendation was 6% for 2010 Centers for Disease Control and Prevention guidelines, 4.3% for neonatal EOS calculator, and 3.3% for local 2016 and 2019 EOS algorithms. CONCLUSIONS: Of the 4 approaches reviewed, the local 2019 EOS algorithm and the neonatal EOS calculator were similar in recommending the lowest frequency of laboratory evaluation and the local 2016 and 2019 EOS algorithms had the lowest recommended antibiotic usage in this population.

No abstract

BACKGROUND AND OBJECTIVES: Overuse of antibiotics in NICUs is a problem worldwide. Unnecessary antibiotic exposure leads to resistance, changes in the microbiome, and increases the risk of bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis (LOS), and mortality in neonates. We aimed to safely reduce the antibiotic usage rate (AUR) in our level IV unit by 10% by December 2018. METHODS: A multidisciplinary quality improvement project took place as part of a Vermont Oxford Network initiative in 2018. Multiple interventions took place, including identification of variations in practices and subsequent standardization through the creation of early onset and LOS guidelines, mass education, improved visibility of the guidelines, and standardized documentation. The main outcome measure for this project was the AUR for infants born <35 weeks’ gestation expressed as antibiotic doses per 1000 patient days. RESULTS: The AUR decreased from a mean of 524 to 394, for a decrease of 24.8%. Results have been sustained for 3 years. Main contributors that led to the sustained success include decreasing the overall use of antibiotics for early onset sepsis, as well as the duration when cultures are negative. The number of LOS courses also decreased slightly. We noted no cases of inadequately treated sepsis resulting in subsequent positive cultures. CONCLUSIONS: Creation of guidelines with mass education and ongoing feedback/monitoring can result in a safe reduction of AUR in the NICU.