Inhibitory Effects of Ethanol on the NLRP3 Inflammasome

Immunosuppression is a major complication of alcoholism and contributes to increased rates of opportunistic infections and sepsis associated with the addiction. The NLRP3 inflammasome is a central intracellular pattern recognition receptor within the innate immune system, which leads to the cleavage and secretion of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Ethanol has been reported to inhibit IL-1β secretion, and here we verify that the alcohol can specifically inhibit activation of the NLRP3 inflammasome resulting in attenuated IL-1β and caspase-1 cleavage and secretion, as well as ASC secretion in response to several agonists. These results were found to be independent of the activation of GABAA receptors or the inhibition of NMDA receptors. Ethanol was only partially able to prevent IL-1β secretion subsequent to NLRC4 activation and was incapable of preventing NLRP1b dependent IL-1β secretion, which are both largely independent of the adapter protein ASC, and ethanol was shown to prevent the formation of ASC specks. Treatment of cells with ethanol resulted in markedly decreased global tyrosine phosphorylation, while administration of the tyrosine phosphatase inhibitor sodium orthovanadate prior to ethanol restored IL-1β secretion. Multiple alcohol containing organic compounds exerted inhibitory effects on the NLRP3 inflammasome parallel to ethanol; however, isoamyl alcohol’s non-alcohol analog, 2-methylbutane, did not. Together, these results show that ethanol antagonizes the NLRP3 inflammasome at an apical event in its activation potentially through the stimulation of protein tyrosine phosphatases. As other short chain alcohols retain this ability, this effect could be dependent on the hydroxyl group of these compounds

To Market, To Market, To Analyze Farming Subsidies

This poster was presented at the National Collegiate Honors Council Conference, Denver, Colorado.https://scholarworks.uttyler.edu/student_posters/1028/thumbnail.jp

Improving Restraint Feasibility through Ambulance Layout Redesign

This study examined the duties performed by emergency medical service workers with the goal of increasing the time EMS workers are restrained while providing patient care during transport. An optimal layout of equipment and materials in the rear patient cabin of an ambulance was created increase seatbelt restraint feasibility for working medics. Over 13,000 EMS agency call logs were evaluated to identify medical procedures frequently performed during patient transports, which were then filmed and analyzed using Pareto and link analysis to measure restraint feasibility. An alternative ambulance layout was developed following focus group meetings, and the adjusted tasks restraint feasibilities were calculated for the alternative layout. Restraint feasibility was significantly increased for the 5th percentile female, 50th percentile male, and 95th percentile male anthropometric populations. The proposed patient compartment design increased overall restraint feasibility from 47 percent to 90 percent. The proposed design would increase safety for medics and patients during patient transports by increasing the number of tasks that could be performed from a belted and seated position

The Social Role Theory of Unethical Leadership

Challenging the standard reasoning regarding leaders’ ethical failures, we argue that a potent contributor to these failures is the social role expectations of leaders. We maintain that leaders’ central role expectation of goal achievement contributes to the over-valuing of group goals and greater moral permissibility of the means used to achieve these goals. In studies 1 and 2 we demonstrated that the role of leader, relative to group member, is associated with an increased appraisal of group goals which is predicted by the leaders’ role expectations and not driven by the psychological effects of power. Next, we experimentally demonstrated the importance of both role expectations of leadership and group goal importance in leaders’ justification to engage in morally questionable behavior to achieve group goals. Finally, we supported the social role predictions in a laboratory experiment by assigning people to roles and assessing goal importance and unethical decision-making and behaviors

Randomized Trial of a Single-Session Growth Mind-Set Intervention for Rural Adolescents’ Internalizing and Externalizing Problems

Objective. Adolescents living in rural regions of the United States face substantial barriers to accessing mental health services, creating needs for more accessible, non-stigmatizing, briefer interventions. Research suggests that single-session “growth mindset” interventions (GM-SSIs)—which teach the belief that personal traits are malleable through effort—may reduce internalizing and externalizing problems in adolescents. However, GM-SSIs have not been evaluated among rural youth, and their effects on internalizing and externalizing problems have not been assessed within a single trial, rendering their relative benefits for different problem types unclear. We examined whether a computerized GM-SSI could reduce depressive symptoms, social anxiety symptoms, and conduct problems in adolescent girls from rural areas of the U.S. Method. Tenth-grade girls (N=222, M age=15.2, 38% white, 25% Black, 29% Hispanic) from four rural, low-income high schools in the Southeastern United States were randomized to receive a 45-minute GM-SSI or a computer-based, active control program, teaching healthy sexual behaviors. Girls self-reported depression symptoms, social anxiety symptoms, and conduct problem behaviors at baseline and four-month follow-up. Results. Relative to girls in the control group, girls receiving the GM-SSI reported modest but significantly greater reductions in depressive symptoms (d=.23) and likelihood of reporting elevated depressive symptoms (d=.29) from baseline to follow-up. GM-SSI effects were nonsignificant for social anxiety symptoms, although a small effect size emerged in the hypothesized direction (d=.21), and nonsignificant for change in conduct problems (d=.01). Conclusions. A free-of-charge, 45-minute GM-SSI may help reduce internalizing distress, especially depression—but not conduct problems—in rural adolescent girls

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Organic matter cycling along geochemical, geomorphic and disturbance gradients in forests and cropland of the African Tropics – Project TropSOC Database Version 1.0

The African Tropics are hotspots of modern-day land-use change and are, at the same time, of great relevance for the cycling of carbon (C) and nutrients between plants, soils and the atmosphere. However, the consequences of land conversion on biogeochemical cycles are still largely unknown as they are not studied in a landscape context that defines the geomorphic, geochemically and pedological framework in which biological processes take place. Thus, the response of tropical soils to disturbance by erosion and land conversion is one of the great uncertainties in assessing the carrying capacity of tropical landscapes to grow food for future generations and in predicting greenhouse gas fluxes (GHG) from soils to the atmosphere and, hence, future earth system dynamics. Here, we describe version 1.0 of an open access database created as part of the project &ldquo;Tropical soil organic carbon dynamics along erosional disturbance gradients in relation to variability in soil geochemistry and land use&rdquo; (TropSOC). TropSOC v1.0 contains spatial and temporal explicit data on soil, vegetation, environmental properties and land management collected from 136 pristine tropical forest and cropland plots between 2017 and 2020 as part of several monitoring and sampling campaigns in the Eastern Congo Basin and the East African Rift Valley System. The results of several laboratory experiments focusing on soil microbial activity, C cycling and C stabilization in soils complement the dataset to deliver one of the first landscape scale datasets to study the linkages and feedbacks between geology, geomorphology and pedogenesis as controls on biogeochemical cycles in a variety of natural and managed systems in the African Tropics. The hierarchical and interdisciplinary structure of the TropSOC database allows for linking a wide range of parameters and observations on soil and vegetation dynamics along with other supporting information that may also be measured at one or more levels of the hierarchy. TropSOC&rsquo;s data marks a significant contribution to improve our understanding of the fate of biogeochemical cycles in dynamic and diverse tropical African (agro-)ecosystems. TropSOC v1.0 can be accessed through the supplementary material provided as part of this manuscript or as a separate download via the websites of the Congo Biogeochemistry observatory and the GFZ data repository where version updates to the database will be provided as the project develops.</p

Implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda: stakeholder engagement meeting report

A Stakeholder engagement meeting on the implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda was held in Nairobi, Kenya, on 27 September 2023. Representatives from the respective National Malaria Control Programmes, the World Health Organization (WHO) Geneva, Africa Regional and Kenya offices, research partners, non-governmental rganizations, and the Medicines for Malaria Venture participated. PDMC was recommended by the WHO in June 2022 and involves provision of a full anti-malarial treatment course at regular intervals during the post-discharge period in children hospitalized with severe anaemia in areas of moderate-to-high malaria transmission. The WHO recommendation followed evidence from a meta-analysis of three clinical trials and from acceptability, delivery, cost-ffectiveness, and modelling studies. The trials were conducted in The Gambia using monthly sulfadoxine-pyrimethamine during the transmission season, in Malawi using monthly artemether-lumefantrine, and in Kenya and Uganda using monthly dihydroartemisinin-piperaquine, showing a significant reduction in all-cause mortality by 77% (95% CI 30–98) and a 55% (95% CI 44–64) reduction in all-cause hospital readmissions 6 months post-discharge. The recommendation has not yet been implemented in sub-Saharan Africa. There is no established platform for PDMC delivery. The objectives of the meeting were for the participating countries to share country contexts, plans and experiences regarding the adoption and implementation of PDMC and to explore potential delivery platforms in each setting. The meeting served as the beginning of stakeholder engagement within the PDMC Saves Lives project and will be followed by formative and implementation research to evaluate alternative delivery strategies in selected countries. Meeting highlights included country consensus on use of dihydroartemisinin-piperaquine for PDMC and expansion of the target group to "severe anaemia or severe malaria", in addition to identifying country-specific options for PDMC delivery for evaluation in implementation research. Further exploration is needed on whether the age group should be extended to school-age children

It is Not All About the Benjamins: Understanding Preferences for Mates with Resources

We contend that preferences for mates with resources or money might be calibrated on where a potential mate gets her/his money. In three studies (N= 668) we examined the nature of individuals' preferences for mates who have resources or money. Both sexes preferred a long-term mate who has earned her/his money over other sources. In particular, women preferred mates who earned their money over other potential means of getting resources (i.e., inheritance, embezzlement, and windfall). Women maintained a high level of interest in mates who earned their money regardless of duration of the mateship whereas men became less interested in a mate who earned her money in the context of short-term relationships. Overall, the sexes preferred a mate who earned their money more strongly in the long-term than the short-term context. Results are discussed from evolutionary and sociocultural models of mate preferences