Despite effective and widely available suppressive anti-HIV therapy, the prevalence of mild neurocognitive dysfunction continues to increase. HIV-associated neurocognitive disorder (HAND) is a multifactorial disease with sustained central nervous system inflammation and immune activation as prominent features. Inflammatory macrophages, HIV-infected and uninfected, play a central role in the development of HIV dementia. There is a critical need to identify biomarkers and to better understand the molecular mechanisms leading to cognitive dysfunction in HAND. In this regard, we identified through a subtractive hybridization strategy osteopontin (OPN, SPP1, gene) an inflammatory marker, as an upregulated gene in HIV-infected primary human monocyte-derived macrophages. Knockdown of OPN in primary macrophages resulted in a threefold decrease in HIV-1 replication. Ectopic expression of OPN in the TZM-bl cell line significantly enhanced HIV infectivity and replication. A significant increase in the degradation of the NF-κB inhibitor, IκBα and an increase in the nuclear-to-cytoplasmic ratio of NF-κB were found in HIV-infected cells expressing OPN compared to controls. Moreover, mutation of the NF-κB binding domain in the HIV-LTR abrogated enhanced promoter activity stimulated by OPN. Interestingly, compared to cerebrospinal fluid from normal and multiple sclerosis controls, OPN levels were significantly higher in HIV-infected individuals both with and without neurocognitive disorder. OPN levels were highest in HIV-infected individuals with moderate to severe cognitive impairment. Moreover, OPN was significantly elevated in brain tissue from HIV-infected individuals with cognitive disorder versus those without impairment. Collectively, these data suggest that OPN stimulates HIV-1 replication and that high levels of OPN are present in the CNS compartment of HIV-infected individuals, reflecting ongoing inflammatory processes at this site despite anti-HIV therapy.

Using water budget data from published literature, we demonstrate how hydrologic processes govern the function of various stormwater infrastructure technologies. Hydrologic observations are displayed on a Water Budget Triangle, a ternary plot tool developed to visualize simplified water budgets, enabling side‐by‐side comparison of green and grey approaches to stormwater management. The tool indicates ranges of hydrologic function for green roofs, constructed wetlands, cisterns, bioretention, and other stormwater control management structures. Water budgets are plotted for several example systems to provide insight on structural and environmental design factors, and seasonal variation in hydrologic processes of stormwater management systems. Previously published water budgets and models are used to suggest appropriate operational standards for several green and grey stormwater control structures and compare between conventional and low‐impact development approaches. We compare models, characterize and quantify water budgets and expected ranges for green and grey infrastructure systems, and demonstrate how the Water Budget Triangle tool may help users to develop a data‐driven approach for understanding design and retrofit of green stormwater infrastructure.

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