Cystic fibrosis (CF) patients undergo progressive airway destruction caused in part by chronic neutrophilic inflammation. While opportunistic pathogens infecting CF airways can cause inflammation, we hypothesized that host-derived metabolic and stress signals would also play a role in this process. We show that neutrophils that have entered CF airways have increased phosphorylation of the eukaryotic initiation factor 4E and its partner the 4E-binding protein 1; 2 key effectors in the growth factor-and amino acid-regulated mammalian target of rapamycin (mTOR) pathway. Furthermore CF airway neutrophils display increased phosphorylation of the cAMP response element binding protein (CREB), a major transcriptional coactivator in stress signaling cascades. These active intracellular pathways are associated with increased surface expression of critical adaptor molecules, including the growth factor receptor CD114 and the receptor for advanced glycation end-products (RAGE), a CREB inducer and sensor for host-derived damage-associated molecular patterns (DAMPs). Most CF airway fluids lack any detectable soluble RAGE, an inhibitory decoy receptor for DAMPs. Concomitantly, CF airway fluids displayed high and consequently unopposed levels of S100A12; a potent mucosa-and neutrophil-derived DAMP. CF airway neutrophils also show increased surface levels of 2 critical CREB targets, the purine-recycling enzyme CD39 and the multifunctional, mTORinducing CXCR4 receptor. This coordinated set of events occurs in all patients, even in the context of minimal airway inflammation and well-preserved lung function. Taken together, our data demonstrate an early and sustained activation of host-responsive metabolic and stress pathways upon neutrophil entry into CF airways, suggesting potential targets for therapeutic modulation.CFTR ͉ EN-RAGE ͉ flow cytometry ͉ S6 ribosomal protein ͉ stromal derived factor-1
We assessed the feasibility, acceptability, and initial impact of a church-based educational program to promote breast, cervical, and colorectal cancer screening among Latinas ages 18 and over. We used a one-group pre/post evaluation within a low-income, Latino Baptist church in Boston, MA. Participants completed interviewer-administered assessments at baseline and at the end of the six-month intervention. Under the guidance of a patient navigator (PN), women from the church (peer health advisors, or PHAs) were trained to deliver evidence-based screening interventions, including one-to-one outreach, small group education, client reminders, and reduction of structural barriers to screening. The PN and PHAs also implemented a health fair and the pastor integrated health information into regular sermons. At pre-intervention, nearly half of the sample did not meet screening guidelines. The majority (97%, n = 35) of those who completed the post-intervention assessment participated in intervention activities. Two-thirds (67%) reported talking with the PN or PHAs about health issues. Participation in small group education sessions was highest (72%), with health fairs (61%), and goal setting (50%) also being popular activities. Fourteen percent also reported receiving help from the PN to access screening tests. This study supports the feasibility and acceptability of churches as a setting to promote cancer screening among Latinas.
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