No abstract

No abstract

Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a well-recognized stimulator derived from gram-negative (G) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs). The main type of EVs found in the early stages after LPS stimulation are apoptotic bodies (ABs) and not microvesicles (MVs) or exosomes (Exos). Furthermore, LPS markedly up-regulate the levels of a repertoire of microRNAs (miRNAs) in the macrophage-derived ABs, including miR-221 and miR-222. Functionally, the LPS-induced, macrophage-derived ABs promote the proliferation of malignant and/or normal lung epithelial cells. We next directly transfected miR-221 and/or miR-222 inhibitors into the LPS-induced ABs. Deletion of miR-221/222 in ABs significantly reduces the AB-mediated proliferation of lung epithelial cells. Mechanistically, AB-shuttling miR-221/222 promote cell growth by modulating cyclin-dependent kinase inhibitor 1B (CDKN1B) pathways. Collectively, LPS-induced, macrophage-derived ABs promote the proliferation of their recipient epithelial cells, partially via AB-shuttling miRNAs.

No abstract

Background An increasing number of U.S. emergency departments (EDs) have implemented ED-based HIV testing programs since the Centers for Disease Control and Prevention issued revised HIV testing recommendations for clinical settings in 2006. In 2010, the National HIV/AIDS Strategy (NHAS) set an LTC rate goal of 85% within 90 days of HIV diagnosis. Linkage to care (LTC) rates for newly diagnosed HIV-infected patients vary markedly by site, and many are suboptimal. The optimal approach for LTC in the ED setting remains unknown. Objective To perform a brief descriptive analysis of the LTC methods practiced in EDs across the United States in order to determine the overall linkage rate of ED-based HIV testing programs. Methods We conducted a systematic review of literature related to U.S. ED HIV testing in the adult population using PubMed, Embase, Web of Science, Scopus and Cochrane. There were 333 articles were identified; 31 articles were selected after a multiphasic screening process. We analyzed data from the 31 articles to assess LTC methods and rates. LTC methods that involved physical escort of the newly diagnosed patient to an HIV/infectious disease (ID) clinic or interaction with a specialist health care provider at the ED were operationally defined as ‘intensive” LTC protocol. “Mixed” LTC protocol was defined as a program that employed intensive linkage only part of the coverage hours. All other forms of linkage was defined as “non-intensive” LTC protocol. An LTC rate of ≥85% was used to identify characteristics of ED-based HIV testing program associated with a higher LTC rate. Results There were 37 ED-based HIV testing programs in the 31 articles. The overall LTC rate was 74.4%. Regarding type of protocol, 9 (24.3%) employed intensive LTC protocols, 25 (67.6%) non-intensive, 2 (5.4%) mixed, and 1 (2.7%) had unclear protocols. LTC rates for programs with intensive and non-intensive LTC protocols were 80.0% and 72.7%, respectively. Four (44.4%) with intensive protocols and nine (36.0%) with the non-intensive protocols had LTC rates >85%. The linkage staff employed was different between ED programs. Among them, 25 (67.6%) programs used exogenous staff, ten (27.0%) used the ED staff, and 2 had no information. All the programs in the non-intensive group utilized drop-in HIV/ID clinic or medical appointments while seven out of nine of the programs in the intensive group physically escorted the patients to the initial medical intake appointment. There were no significant differences in characteristics of ED-based HIV testing programs between those with ≥85% LTC rate versus those with <85% within the intensive or non-intensive group. Conclusion Intensive LTC protocols had a higher LTC rate and a higher proportion of programs that surpassed the >85% NHAS goal as compared to non-intensive methods, suggesting that, when possible, ED-based HIV testing programs should adopt intensive LTC strategies to improve LTC outcomes. However, intensive LTC protocols most often required involvement of multidisciplinary n...