IL-17 is indirect and possibly due to the effect of hypoxia on several pro-inflammatory pathways and influx of inflammatory immune cells into inflamed joint. Hypoxia did induce IL-6 levels in monocyte, suggesting that hypoxia induces differential cytokine signaling pathways which may depend on cell-type. This is consistent with our previous work in which we demonstrated that patients with low in vivo measures of tpO2 were significantly associated with high CD3+T cells and CD68 macrophages infiltrates and increased expression of TNFa, IL-1b, IFN-c and MIP-3a. The effect of hypoxia on proinflammatory mediators has been demonstrated by several in vitro studies showing induction of TNFa, IL-1b, VEGF. Induction of macrophage inflammatory protein CCL20 in SF monocytes and ICAM in lymphocytes following exposure to hypoxia has also been demonstrated. Whether hypoxia is driving the increase of IL-17A expression in the joint or whether it is due to increased inflammation is unclear. The association of hypoxia with inflammatory cells and MIP-3a induction would support a role for a hypoxia-induced influx of inflammatory immune cells as MIP-3a is involved in attracting IL-17A positive cells to the joint. However, several studies have suggested that TH17 cells do not acquire a fully activated phenotype until they are resident within the inflammatory joint where the presence of soluble mediators and ALK5 Inhibitor II ALK inhibitor cell-cell interactions influence their differentiation. In conclusion we have localised IL-17A expression to neutrophils and mast cells in inflamed human synovium, with highest positivity demonstrated on neutrophils. The expression of IL-17A in the serum, SF and tissue of inflammatory arthritis patients was associated with inflammation and cellular infiltrate. While no direct relationship between hypoxia and IL-17A production was established, hypoxia may influence IL-17A expression by upregulating production of various soluble mediators, in addition to induction of leukocyte influx into the synovium inflammatory processes. The HIV/AIDS prevalence was 0.6% in the adult population, one of the highest in Western Europe. After an initial period dominated by homosexual transmission of HIV-1, a shift towards transmission through heterosexual contacts and drug injection occurred and, today, heterosexual contact is the main route of HIV-1 transmission in Portugal. African and Brazilian immigrants contribute substantially for the number of AIDS cases in this category. The current HIV-1 epidemic in Portugal is caused by multiple subtypes, with predominance of subtype B followed by G. The high prevalence of these two subtypes has promoted the appearance of different types of B/G recombinant strains. CRF14_BG was the first epidemic CRF composed of subtypes B and G to be characterized by full-genome sequencing. This CRF was first isolated in 2002 from intravenous drug users in Galiza, Spain. CRF14_BG displays a mosaic structure with two inter-subtype breakpoints delimiting a B subtype segment comprising most of gp120 and the 59 half of gp41, whereas all remaining regions are classified as subtype G.