Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation

It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg+) mice, airway-targeted overexpression of the epithelial Na+ channel β subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg+ mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg+ mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll/Interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg+ mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg+ mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg+ mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation

Small scale migration along the interoceanic highway in Madre de Dios, Peru: an exploration of community perceptions and dynamics due to migration.

BACKGROUND: Madre de Dios, a southern state in the Peruvian Amazon basin, has experienced rapid development as well as an influx of migrants since the construction of the Interoceanic Highway (IOH) connecting Brazil, Bolivia, and the Peruvian coast. We explored perceptions of migration and development in up to eight communities along the IOH in Madre de Dios following construction of the highway. METHODS: We conducted a multiple methods study involving focus group (FG) discussions and interviews with key informants (KIs) in eight communities in Madre de Dios. The data was used to develop and apply a survey on demographics, financial, personal, social, human, and physical capital in four communities between February 2014 and March 2015. RESULTS: We conducted 12 FGs and 34 KI interviews. A total of 522 people participated in the survey. Comparing migrants (those who had moved to the area after construction of the IOH) and non-migrants, we found no difference in food security or access to health services. The majority (67.6%) of respondents from both groups reported that illness was their primary threat to well-being. Non-migrants owned more land than migrants (p < 0.001), were more likely to have piped water directly in their home (p = 0.046), and were more likely to participate in community groups (p = 0.012). Looking at perceptions about migrants, KIs and FGs discussed both positive perceptions of migrants (increased cultural exchange and new technology) and negative perceptions (increased drugs and alcohol in their communities and a lack of investment in the community). Both migrants and non-migrants reported trusting the local government more than the national government. CONCLUSIONS: Although we hypothesized that migrants would have decreased access to food, water, health services, and land relative to non-migrants, our results show that the only significant differences were in land ownership and water access. Efforts to improve community infrastructure should be carried out at the local level and focus on improving issues reported by both groups, such as potable water, sewage, and increased access to health services. Furthermore, an emphasis on community cohesion, ensuring land rights, and increasing long-term job opportunities should help ease tensions between migrants and non-migrants

The Impact of Road Construction on Subjective Well-Being in Communities in Madre de Dios, Peru.

The interoceanic highway (IOH) in Madre de Dios, Peru has driven dramatic change in the Peruvian Amazon basin. We conducted a mixed methods study to examine the impact of these changes on the subjective well-being (SWB) of four communities on the IOH. Themes that emerged qualitatively included changing health threats, environmental degradation, and the impact of increased migration. To achieve a higher level of SWB, respondents emphasized the need for higher incomes, opportunities to learn new skills, and a better education for their children. Potential threats to SWB included marital problems and poorer health. Quantitative analyses suggested that social support and a sense of security impacted reported SWB scores based on life satisfaction, and the impact of income on life satisfaction was mediated by food security. Although long-term residents felt that specific determinants of SWB had both increased (food variety, transport and access to work) and decreased (access to natural resources and hunting), the majority reported that their lives had improved overall. Health had been affected by the IOH in both negative ways (increased dengue and road accidents) and positive ways (improved access to health services). Our results suggest that the rapidly-changing communities near the IOH link well-being to health, income, community, and the environment

Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity

SummaryThe selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

Innovative Visualizations Shed Light on Avian Nocturnal Migration

We acknowledge the support provided by COST–European Cooperation in Science and Technology through the Action ES1305 ‘European Network for the Radar Surveillance of Animal Movement’ (ENRAM) in facilitating this collaboration. We thank ENRAM members and researchers attending the EOU round table discussion ‘Radar aeroecology: unravelling population scale patterns of avian movement’ for feedback on the visualizations. We thank Arie Dekker for his feedback as jury member of the bird migration visualization challenge & hackathon hosted at the University of Amsterdam, 25–27 March 2015. We thank Willem Bouten and Kevin Winner for discussion of methodological design. We thank Kevin Webb and Jed Irvine for assistance with downloading, managing, and reviewing US radar data. We thank the Royal Meteorological Institute of Belgium for providing weather radar data.Globally, billions of flying animals undergo seasonal migrations, many of which occur at night. The temporal and spatial scales at which migrations occur and our inability to directly observe these nocturnal movements makes monitoring and characterizing this critical period in migratory animals’ life cycles difficult. Remote sensing, therefore, has played an important role in our understanding of large-scale nocturnal bird migrations. Weather surveillance radar networks in Europe and North America have great potential for long-term low-cost monitoring of bird migration at scales that have previously been impossible to achieve. Such long-term monitoring, however, poses a number of challenges for the ornithological and ecological communities: how does one take advantage of this vast data resource, integrate information across multiple sensors and large spatial and temporal scales, and visually represent the data for interpretation and dissemination, considering the dynamic nature of migration? We assembled an interdisciplinary team of ecologists, meteorologists, computer scientists, and graphic designers to develop two different flow visualizations, which are interactive and open source, in order to create novel representations of broad-front nocturnal bird migration to address a primary impediment to long-term, large-scale nocturnal migration monitoring. We have applied these visualization techniques to mass bird migration events recorded by two different weather surveillance radar networks covering regions in Europe and North America. These applications show the flexibility and portability of such an approach. The visualizations provide an intuitive representation of the scale and dynamics of these complex systems, are easily accessible for a broad interest group, and are biologically insightful. Additionally, they facilitate fundamental ecological research, conservation, mitigation of human–wildlife conflicts, improvement of meteorological products, and public outreach, education, and engagement.Yeshttp://www.plosone.org/static/editorial#pee

Quality Over Quantity: Buffer Strips can be Improved with Select Native Plant Species

Native plants attractive to beneficial insects may improve the value of buffer strips by increasing biodiversity and enhancing the delivery of insect-derived ecosystem services. In a 2-yr field experiment, we measured the response of insect communities across nine buffers that varied in plant diversity. We constructed buffers with plants commonly found in buffers of USDA-certified organic farms in Iowa (typically a single species), recommended for prairie reconstruction, or recommended for attracting beneficial insects. We hypothesized that the diversity and abundance of beneficial insects will be 1) greatest in buffers composed of diverse plant communities with continuous availability of floral resources, 2) intermediate in buffers with reduced species richness and availability of floral resources, and 3) lowest in buffers composed of a single species. We observed a significant positive relationship between the diversity and abundance of beneficial insects with plant community diversity and the number of flowers. More beneficial insects were collected in buffers composed of species selected for their attractiveness to beneficial insects than a community recommended for prairie restoration. These differences suggest 1) plant communities that dominate existing buffers are not optimal for attracting beneficial insects, 2) adding flowering perennial species could improve buffers as habitat for beneficial insects, 3) buffers can be optimized by intentionally combining the most attractive native species even at modest levels of plant diversity, and 4) plant communities recommended for prairie reconstruction may not contain the optimal species or density of the most attractive species necessary to support beneficial insects from multiple guilds.This article is from Environmental Entomology 43 (2014): 298–311, doi:10.1603/EN13027. Posted with permission.</p