Davidsenhanna7341

BACKGROUND AND OBJECTIVES The Vaccines for Children Program (VFC) provides vaccines for children who may not otherwise be vaccinated because of financial barriers. Pediatrician participation is crucial to the VFC's ongoing success. Our objectives were to assess, among a national sample of pediatricians, (1) VFC program participation, (2) perceived burden versus benefit of participation, and (3) knowledge and perception of a time-limited increased payment for VFC vaccine administration under the Patient Protection and Affordable Care Act. METHODS An electronic and mail survey was conducted from June 2017 to September 2017. RESULTS Response rate was 79% (372 of 471); 86% of pediatricians reported currently participating in the VFC; among those, 85% reported never having considered stopping, 10% considered it but not seriously, and 5% seriously considered it. Among those who had considered no longer participating (n = 47), the most commonly reported reasons included difficulty meeting VFC record-keeping requirements (74%), concern about action by the VFC for noncompliance (61%), and unpredictable VFC vaccine supplies (59%). Participating pediatricians rated, on a scale from -5 (high burden) to +5 (high benefit), their overall perception of the VFC 63% reported +4 or +5, 23% reported +1 to +3, 5% reported 0, and 9% reported -1 to -5. Of pediatricians, 39% reported awareness of temporary increased payment for VFC vaccine administration. Among those, 10% reported that their practice increased the proportion of Medicaid and/or VFC-eligible patients served on the basis of this change. CONCLUSIONS For most pediatricians, perceived benefits of VFC participation far outweigh perceived burdens. To ensure the program's ongoing success, it will be important to monitor factors influencing provider participation. Copyright © 2020 by the American Academy of Pediatrics.Viruses are known to perturb host cellular metabolism to enable their replication and spread. However, little is known about the interactions between Zika virus (ZIKV) infection and host metabolism. Using primary human retinal vascular endothelial cells and an established human endothelial cell line, we investigated the role of AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, in response to ZIKV challenge. ZIKV infection caused a time-dependent reduction in the active phosphorylated state of AMPK and of its downstream target acetyl-CoA carboxylase. Pharmacological activation of AMPK using 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), metformin, and a specific AMPKα activator (GSK621) attenuated ZIKV replication. This activity was reversed by an AMPK inhibitor (compound C). Lentivirus-mediated knockdown of AMPK and the use of AMPKα-/- mouse embryonic fibroblasts provided further evidence that AMPK has an antiviral effect on ZIKV replication. Consistent with its antiviral effect, AMPK activation potentiated the expression of genes with antiviral properties (e.g., IFNs, OAS2, ISG15, and MX1) and inhibited inflammatory mediators (e.g., TNF-α and CCL5). Bioenergetic analysis showed that ZIKV infection evokes a glycolytic response, as evidenced by elevated extracellular acidification rate and increased expression of key glycolytic genes (GLUT1, HK2, TPI, and MCT4); activation of AMPK by AICAR treatment reduced this response. Consistent with this, 2-deoxyglucose, an inhibitor of glycolysis, augmented AMPK activity and attenuated ZIKV replication. Thus, our study demonstrates that the anti-ZIKV effect of AMPK signaling in endothelial cells is mediated by reduction of viral-induced glycolysis and enhanced innate antiviral responses. Copyright © 2020 by The American Association of Immunologists, Inc.IL-23 and IL-12, two structurally related heterodimeric cytokines sharing a common subunit, divergently promote Th cell development and expansion. Both cytokines have been implicated in the pathogenesis of thyroid-associated ophthalmopathy (TAO), an autoimmune component of Graves disease. In TAO, CD34+ fibrocytes, putatively derived from bone marrow, can be identified in the orbit. There they masquerade as CD34+ orbital fibroblasts (OF) (CD34+ OF) and cohabitate with CD34- OF in a mixed fibroblast population (GD-OF). Slit2, a neural axon repellent, is expressed and released by CD34- OF and dampens the inflammatory phenotype of fibrocytes and CD34+ OF. In this study we report that thyrotropin (TSH) and the pathogenic, GD-specific monoclonal autoantibody, M22, robustly induce IL-23 in human fibrocytes; however, IL-12 expression is essentially undetectable in these cells under basal conditions or following TSH-stimulation. In contrast, IL-12 is considerably more inducible in GD-OF, cells failing to express IL-23. This divergent expression and induction of cytokines appears to result from cell type-specific regulation of both gene transcription and mRNA stabilities. It appears that the JNK pathway activity divergently attenuates IL-23p19 expression while enhancing that of IL-12p35. The shift from IL-23p19 expression in fibrocytes to that of IL-12p35 in their derivative CD34+ OF results from the actions of Slit2. Thus, Slit2 might represent a molecular determinant of balance between IL-23 and IL-12 expression, potentially governing immune responses in TAO. Copyright © 2020 by The American Association of Immunologists, Inc.STUDY OBJECTIVES To compare the prices paid for nicotine vaping products (NVPs) and supplies among current NVP users to prices paid for cigarettes among current smokers. DATA The 2016 International Tobacco Control Four Country Vaping and Smoking Survey (4CV1). Key measures included (1) self-reported prices paid for reusable NVPs (eg, rechargeable devices with cartridges and tank system devices with e-liquids) in the 3-month period prior to the survey among current NVP users, (2) prices paid for disposable NVPs, cartridges and e-liquids purchased in the last 30 days among current NVP users and (3) self-reported prices paid for cigarettes among current smokers. RESULTS Disposable NVP price was higher than the price of a comparable unit for combustible cigarettes in England (EN), USA and Canada (CA). Valproic acid Prefilled cartridge price was higher than the price of a comparable unit of cigarettes in USA and CA, but lower in EN and Australia. E-liquid price was consistently lower than the price of a comparable unit of cigarettes across four countries.