From Design to Dissemination: Implementing Community-Based Participatory Research in Postdisaster Communities.

OBJECTIVES: To review how disasters introduce unique challenges to conducting population-based research and community-based participatory research (CBPR). METHODS: From 2007-2009, we conducted the Head-off Environmental Asthma in Louisiana (HEAL) Study in the aftermath of Hurricane Katrina in a Gulf Coast community facing an unprecedented triple burden: Katrina's and other disasters' impact on the environment and health, historic health disparities, and persistent environmental health threats. RESULTS: The unique triple burden influenced every research component; still, most existing CBPR principles were applicable, even though full adherence was not always feasible and additional tailored principles govern postdisaster settings. CONCLUSIONS: Even in the most challenging postdisaster conditions, CBPR can be successfully designed, implemented, and disseminated while adhering to scientific rigor.

Habitat-related divergence among tailfan sensory systems in reptantian Decapod crustaceans.

Squat lobsters (Galatheidae) and mole sand crabs (Hippidae) differ in posture and locomotion from each other and from crayfish, their surrogate ancestor for neurobehavioral features. Galatheids resemble crayfish more closely in general behavior and niche, but are intermediate between crayfish and hippids with respect to morphology and neuromusculature. The tailfan is inverted under the abdomen in both, due to the flexed abdominal posture, but its morphology has diverged considerably. Nothing is known about adaptations of the tailfan exteroceptors to the new sensory world of either group. We used SEM, vital staining, and extracellular electrophysiological techniques to survey the sensory structures on the telsons of the galatheid Munida quadrispina and the hippid Emerita analoga for comparison with published data on the homologous mechanosensory system in crayfish. Both telsons bear plumose, peg, and non-annulate (natatory or guard) setae. In addition, M. quadrispina has singly-innervated smooth setae and E. analoga a previously undescribed type of small seta the outer face of which is covered by transversely-oriented, thin setules that are much broader than they are long and angled outward toward the seta's distal end, overlapping loosely. The 'stack-of-scales' appearance of its distal portion viewed from the side engendered the name: scaly seta. Some shared features with other small setae that are chemo- and mechanoreceptive suggest scaly setae might be bimodal sensilla. The telson of M. quadrispina is very flexible. Plumose setae on its dorsal surface are arranged into hemi-circlets and most, if not all, appear not to be innervated. They may contribute to adjacent smooth setae's mechanosensitivity via mechanical coupling through adjacent cuticle, as occurs between feathered and smooth setae on crayfish antennae. Sensory nerve recordings show many afferents to have low thresholds to mechanical disturbance, suggesting they are hydrodynamic receptors. The telson of E. analoga is rigid, and all dorsal setae are relegated to the margins. Patches of scaly setae on the anterior lateral dorsal telson are strategically located to sense the substrate when the crabs are in sand. Scaly and peg setae are arrayed along shallow grooves, one along each side, that are flanked laterally by a fringe of plumose and pappose setae. Substantial deflection from resting position of the latter was required to reliably elicit afferent activity, suggesting most function as touch receptors. The different, non-random distributions of tailfan setae match these animals' divergent sensory worlds and might have engendered species-specific alterations in their central sensory systems.

Projection and local interneurons in the sixth abdominal ganglion of the sand crab Emerita analoga (Hippidae).

Hippid crabs are adapted for life in the surf zone of exposed sandy beaches, and their tailfan differs from the tailfans of other crustaceans with respect to morphology and motor control and in having nonspiking stretch receptors (NSR). To investigate how these crabs' mechanosensory systems are adapted to this turbulent environment, I used axonal back-filling and intracellular recording with dye-filled microelectrodes to describe afferent projections from the telson and morphologies and physiological responses of intersegmental and local neurons in abdominal ganglion 6 (A6) in Emerita analoga, then compared them with descriptions of corresponding neurons in A6 of crayfish. The density of afferent terminals and the proportion of projection neuron somata is lower in anterior A6 of E. analoga than in crayfish, perhaps correlated with a reduction in hydrodynamic setae. Many interneurons responded to afferent nerve stimulation and displayed activity correlated with levels of A6 motor output. NSR stretch depolarizes unilateral local neurons and terminals of axons entering A6 from the connective and hyperpolarizes bilateral local and projection neurons. The timing and duration of this inhibition would suppress mechanosensory input from the telson during uropod beating (homologue of crayfish's nongiant tail-flipping). Suppression of reafference during uropod beating may have been pivotal for evolution of hippids' ability to move rapidly across the water-sand interface in the slosh zone of sandy beaches. Homologies between A6 neurons in E. analoga and crayfish, suggested by morphological and physiological similarities, indicate that the NSRs connect to a neuronal network regulating exteroceptive input that was inherited from their tail-flipping ancestors.

Novel small-molecule inhibitors of hepatitis C virus entry block viral spread and promote viral clearance in cell culture.

Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV) infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp) technology. We independently discovered and optimized a series of 1,3,5-triazine compounds that are potent, selective and non-cytotoxic inhibitors of HCV entry. Representative compounds fully suppress both cell-free virus and cell-to-cell spread of HCV in vitro. We demonstrate, for the first time, that long term treatment of an HCV cell culture with a potent entry inhibitor promotes sustained viral clearance in vitro. We have confirmed that a single amino acid variant, V719G, in the transmembrane domain of E2 is sufficient to confer resistance to multiple compounds from the triazine series. Resistance studies were extended by evaluating both the fusogenic properties and growth kinetics of drug-induced and natural amino acid variants in the HCVpp and HCV cell culture assays. Our results indicate that amino acid variations at position 719 incur a significant fitness penalty. Introduction of I719 into a genotype 1b envelope sequence did not affect HCV entry; however, the overall level of HCV replication was reduced compared to the parental genotype 1b/2a HCV strain. Consistent with these findings, I719 represents a significant fraction of the naturally occurring genotype 1b sequences. Importantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection.