Pharmacologic rationale for the NK1R antagonist, aprepitant as adjunctive therapy in HIV.

BACKGROUND: Many HIV infected individuals with suppressed viral loads experience chronic immune activation frequently developing neurological impairment designated as HIV associated neurocognitive disorder (HAND). Adjunctive therapies may reduce HIV associated inflammation and therefore decrease the occurrence of HAND. METHODS: We have conducted in vitro, animal and clinical studies of the neurokinin 1 receptor (NK1R) antagonist aprepitant in HIV/SIV infection. RESULTS: Aprepitant inhibits HIV infection of human macrophages ex vivo with an ED50 ~ 5 µM. When administered at 125 mg once daily for 12 months to SIV-infected rhesus macaques, aprepitant reduced viral load by approximately tenfold and produced anti-anxiolytic effects. The anti-viral and anti-anxiolytic effects occur at approximately the third month of dosing; and the effects are sustained throughout the duration of drug administration. Protein binding experiments in culture media and animal and human plasma indicate that the free fraction of aprepitant is lower than previously reported supporting usage of higher doses in vivo. The analysis of blood samples from HIV positive individuals treated for 2 weeks with aprepitant at doses up to 375 mg demonstrated reduced levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. Decreased pro-inflammatory cytokines may reduce HIV comorbidities associated with chronic inflammation. CONCLUSIONS: Our results provide evidence for a unique combination of antiretroviral, anti-inflammatory and behavioral modulation properties of aprepitant in vitro and in vivo. These results provide robust support for a clinical exposure target above that recommended for chemotherapy-induced nausea and vomiting. Doses up to 375 mg once daily in HIV-infected patients still elicit sub-therapeutic exposure of aprepitant though effective plasma concentrations can be achievable by proper dose modulation.

Coastal Vertebrate Exposure to Predicted Habitat Changes Due to Sea Level Rise.

Sea level rise (SLR) may degrade habitat for coastal vertebrates in the Southeastern United States, but it is unclear which groups or species will be most exposed to habitat changes. We assessed 28 coastal Georgia vertebrate species for their exposure to potential habitat changes due to SLR using output from the Sea Level Affecting Marshes Model and information on the species' fundamental niches. We assessed forecasted habitat change up to the year 2100 using three structural habitat metrics: total area, patch size, and habitat permanence. Almost all of the species (n = 24) experienced negative habitat changes due to SLR as measured by at least one of the metrics. Salt marsh and ocean beach habitats experienced the most change (out of 16 categorical land cover types) across the three metrics and species that used salt marsh extensively (rails and marsh sparrows) were ranked highest for exposure to habitat changes. Species that nested on ocean beaches (Diamondback Terrapins, shorebirds, and terns) were also ranked highly, but their use of other foraging habitats reduced their overall exposure. Future studies on potential effects of SLR on vertebrates in southeastern coastal ecosystems should focus on the relative importance of different habitat types to these species' foraging and nesting requirements. Our straightforward prioritization approach is applicable to other coastal systems and can provide insight to managers on which species to focus resources, what components of their habitats need to be protected, and which locations in the study area will provide habitat refuges in the face of SLR.

Does Nesting Material Affect Wood Duck (Aix sponsa) Nest Box Selection, Reproduction, and Eggshell Bacteria?

Wood Ducks (Aix sponsa) are secondary cavity nesters that use natural cavities and artificial nest boxes, the latter of which has been attributed to the recovery of populations across the southeastern US. Continual use of these boxes results in a buildup of bacteria, parasites, and other pathogens. To avoid the accumulation of these deleterious organisms, best management practices include the occasional removal of old nesting material (i.e., wood shavings) and replacement with fresh wood shavings. No studies have been performed on the effects of shaving material on nest box selection, nest success, and bacterial growth. We monitored 142 and 111 nest boxes in Florida and Georgia, USA, respectively, and filled a random sample with aspen or cedar shavings. We then swabbed the surface of 144 and 150 eggs during 2020 and 2021, respectively, to screen for culturable bacteria. We detected no effect of shaving type on nest box selection, nest success, or egg surface bacterial growth. We found 3-8 bacterial colony types (1-123 colony-forming units [CFU]/box) and 1-8 bacterial colony types (3-382 CFU/box) among the Georgia and Florida samples, respectively. We detected no effect from shaving type on Wood Duck reproduction or bacterial growth in the sampled nest boxes. We concluded that both shaving types are suitable nesting materials for box-nesting Wood Duck populations and the continued use of either would be a reasonable decision for managers.

Urbanisation generates multiple trait syndromes for terrestrial animal taxa worldwide.

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats, species, and functional groups. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities. Using a dataset encompassing six terrestrial faunal taxa (amphibians, bats, bees, birds, carabid beetles and reptiles) across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy showing the strongest response. Our findings suggest that urbanisation results in four trait syndromes (mobile generalists, site specialists, central place foragers, and mobile specialists), with resources associated with reproduction and diet likely driving patterns in traits associated with mobility and body size. Functional diversity measures showed varied responses, leading to shifts in trait space likely driven by critical resource distribution and abundance, and taxon-specific trait syndromes. Maximising opportunities to support taxa with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation and helps ensure that urban environments have the capacity to respond to future challenges. These actions are critical to reframe the role of cities in global biodiversity loss.

Do urban open spaces provide refugia for frogs in urban environments?

Urbanization is among the largest threats to wildlife populations through factors such as fragmentation, isolation, and habitat destruction. Urban open spaces, such as parks and golf courses, have the potential to provide wildlife with suitable habitat within an urbanized matrix. These refugia may be particularly important for amphibians, which represent one of the most endangered and least vagile vertebrate groups on earth. During the spring and summer of 2018, we conducted surveys to determine the presence of anurans at 51 wetland sites within the Piedmont ecoregion of South Carolina. Nearly one-third of these wetlands were located within urban open spaces, one-third in low development areas, and one-third in highly developed areas. Impervious surface and total road length surrounding the wetlands were measured at two scales, a core habitat scale (300 m) and average maximum migration scale (750 m), and we measured several within-wetland habitat variables. Urban Open Space wetlands had levels of surrounding impervious surface similar to High Urbanization wetlands at the larger scale and were intermediate between Low and High Urbanization wetlands at the smaller scale. The total length of road segments occurring within buffers (at both scales) surrounding our study wetlands was higher for Urban Open Space compared to Low and High Urbanization sites. Among the within-wetland variables measured, Low Urbanization sites had higher canopy cover and were more likely to have a terrestrial buffer zone relative to the other categories. Species richness decreased significantly as total road length increased among all wetlands. Wetland category was not a significant driver explaining species richness, but ß-diversity was more variable among Urban Open Space wetlands than either Low or High Urbanization wetlands. Urban Open Space wetlands did not appear to increase suitability for anurans relative to High Urbanization wetlands. Urban Open Space wetlands had higher variability in species composition, which was perhaps attributable to the diversity among sites represented in the Urban Open Space category.

The relationship between biodiversity and wetland cover varies across regions of the conterminous United States.

Identifying the factors that determine the spatial distribution of biodiversity is a major focus of ecological research. These factors vary with scale from interspecific interactions to global climatic cycles. Wetlands are important biodiversity hotspots and contributors of ecosystem services, but the association between proportional wetland cover and species richness has shown mixed results. It is not well known as to what extent there is a relationship between proportional wetland cover and species richness, especially at the sub-continental scale. We used the National Wetlands Inventory (NWI) to model wetland cover for the conterminous United States and the National Land Cover Database to estimate wetland change between 2001 and 2011. We used a Bayesian spatial Poisson model to estimate a spatially varying coefficient surface describing the effect of proportional wetland cover on the distribution of amphibians, birds, mammals, and reptiles and the cumulative distribution of terrestrial endemic species. Species richness and wetland cover were significantly correlated, and this relationship varied both spatially and by taxonomic group. Rather than a continental-scale association, however, we found that this relationship changed more closely among ecoregions. The species richness of each of the five groups was positively associated with wetland cover in some or all of the Great Plains; additionally, a positive association was found for mammals in the Southeastern Plains and Piedmont of the eastern U.S. Model results indicated negative association especially in the Cold Deserts and Northern Lakes & Forests of Minnesota and Wisconsin, though these varied greatly between groups. Our results highlight the need for wetland conservation initiatives that focus efforts at the level II and III ecoregional scale rather than along political boundaries.

Detritus Quality and Locality Determines Survival and Mass, but Not Export, of Wood Frogs at Metamorphosis.

Single-site experiments have demonstrated detritus quality in wetlands can have strongly negative, neutral, and even positive influences on wildlife. However, an examination of the influence of detritus quality across several regions is lacking and can provide information on whether impacts from variation in detritus quality are consistent across species with wide ranges. To address this gap in regional studies we examined effects of emergent and allochthonous detritus of different nutrient qualities on amphibians and assessed a mechanism that may contribute to potential impacts. We used aquatic mesocosms to raise wood frogs (Rana sylvatica) from two regions of the United States with whole plants from purple loosestrife (Lythrum salicaria), leaf litter from native hardwood trees, and a mixture of both. We examined several metrics of amphibian fitness and life history, including survival, number of days to metamorphosis, and size at metamorphosis. Further, we quantified whether the effects of detritus type could translate to variation in anuran biomass or standing stock of nitrogen or phosphorus export. Our results show detritus with high nutrient quality (purple loosestrife) negatively influenced survival of wood frogs, but increased size of metamorphic individuals in two different regions of the United States. Despite the decrease in survival, the increase in size of post-metamorphic anurans raised with high quality detritus resulted in anuran biomass and standing stock of N and P export being similar across treatments at both locations. These results further demonstrate the role of plant quality in shaping wetland ecosystem dynamics, and represent the first demonstration that effects are consistent within species across ecoregional boundaries.

Novel method to predict body weight in children based on age and morphological facial features.

A new and novel approach of predicting the body weight of children based on age and morphological facial features using a three-layer feed-forward artificial neural network (ANN) model is reported. The model takes in four parameters, including age-based CDC-inferred median body weight and three facial feature distances measured from digital facial images. In this study, thirty-nine volunteer subjects with age ranging from 6-18 years old and BW ranging from 18.6-96.4 kg were used for model development and validation. The final model has a mean prediction error of 0.48, a mean squared error of 18.43, and a coefficient of correlation of 0.94. The model shows significant improvement in prediction accuracy over several age-based body weight prediction methods. Combining with a facial recognition algorithm that can detect, extract and measure the facial features used in this study, mobile applications that incorporate this body weight prediction method may be developed for clinical investigations where access to scales is limited.

The influence of sentence novelty and figurativeness on brain activity.

The predominance of the left hemisphere in language comprehension and production is well established. More recently, the right hemisphere's contribution to language has been examined. Clinical, behavioral, and neuroimaging research support the right hemisphere's involvement in metaphor processing. But, there is disagreement about whether metaphors, in and of themselves, engage the right hemisphere or if other factors that vary between metaphors and literal language elicit right hemisphere engagement. It is important to disambiguate these issues to improve our basic knowledge of figurative language processing, to more precisely define how the right hemisphere supports language, and to facilitate our ability to understand and treat language impairments. Here we investigated the role of the right hemisphere in language comprehension with functional magnetic resonance imaging (fMRI) by manipulating familiarity in both literal and metaphoric sentences. In an event-related design, participants viewed English sentences that appeared every 4.5-9s, and to which they made a pleasantness judgment. All sentences elicited activation in traditional language brain regions including left inferior frontal gyrus, left anterior inferior temporal and left posterior middle temporal gyri. Overall, metaphors and novel stimuli elicited activation in bilateral inferior frontal gyri and left temporal regions. Additionally, metaphors elicited greater activation than literal sentences in right temporal pole. Although our results are partially consistent with the graded salience hypothesis and the coarse coding hypothesis, the right hemisphere's sensitivity to familiar metaphors suggests that right hemisphere recruitment is most influenced by semantic integration demands.