Xenobiotic Exposure and Autoimmune Hepatitis

Although genetics contributes to the development of autoimmune diseases, it is clear that “environmental” factors are also required. These factors are thought to encompass exposure to certain drugs and environmental pollutants. This paper examines the mechanisms that normally maintain immune unresponsiveness in the liver and discusses how exposure to certain xenobiotics such as trichloroethylene may disrupt those mechanisms and promote autoimmune hepatitis

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management

To God Be the Glory: Discussing Sex in Evangelical Communities in Southern Nigeria

Many people hold stereotypes and assumptions about religious communities in regards to their feelings and beliefs about sex and the impact it has on the lived experiences of religious people. However, stereotypes and assumptions are not often grounded in reality, and many people are hesitant to address the issue head on. This qualitative ethnographically informed preliminary grounded theory study aimed to engage an Evangelical Pentecostal community in Southern Nigeria with the ultimate goal of understanding how communities conceptualize and discuss sexuality topics, the factors influencing sexual decision making amongst youth and young adults, and to identify research needs that will better inform innovative and efficacious research utilizing religious communities in sexuality research. Results showed that this population was highly interested in discussing sexuality in their community including major threats to their ideal sexual behavior path, reasons why people stray from this ideal and how to keep people on this ideal path. This research demonstrates that religious communities are interested in conducting sexuality research so long as the research takes their values and beliefs into account and respects their limitations when it comes to research intent and methods.Keywords: Sexuality, faith-based, Nigeria, community based research, qualitativ

A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice

Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immu- notoxicity and neurotoxicity. Previous studies have shown that MRLþ/þ mice exposed to TCE from gesta- tion through early-life demonstrate robust increases in inflammatory markers in peripheral CD4þ T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRLþ/þ mice were given 0.5mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthan- ized at 49days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statis- tically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE

The Path to Eliminating Raccoon Rabies in the Eastern US-Obstacles and Opportunities in Urban-Suburban Landscapes

Rabies in terrestrial wildlife poses a significant public and animal health threat. Oral rabies vaccination (ORV) targeting specific vector species has proven effective in eliminating certain rabies variants in Europe and Canada. The goal of eliminating the raccoon rabies variant (RRV) in the US is achievable through an integrated ORV program at the landscape scale. Current wildlife rabies management in the US includes extensive air and ground ORV programs in 16 eastern states coordinated by Wildlife Services (WS)’ National Rabies Management Program. More than 10 million vaccine-baits are distributed annually targeting raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) with the long-term goal of eliminating RRV. Achieving vaccine-induced herd immunity in target species in developed landscapes has proven challenging due to abundant anthropogenic food sources, higher wildlife densities, decreased home ranges, habitat fragmentation, and non-target bait competition. Effectively managing RRV in the urban-suburban landscape requires greater understanding of meso-carnivore ecology in these landscapes and critical analyses of current baiting strategies. Preliminary results from urban-suburban studies demonstrate fewer potential ORV bait encounters for target species than expected, lower seroconversion rates compared to rural habitats and patchy bait distribution patterns. New technologies including the use of Point of Interest GPS units to document ground bait distribution in combination with research conducted by WS including ORV field trials, urban density studies, and raccoon, skunk, and opossum (Didelphis virginiana) ecology have provided valuable insight to overcome the obstacles of urban rabies management and make eliminating RRV a reality

Data-driven management—a dynamic occupancy approach to enhanced rabies surveillance prioritization

Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, National Rabies Management Program (NRMP) collaborates with other agencies to implement broad-scale ORV and conducts extensive monitoring to measure the effectiveness of the management. Enhanced Rabies Surveillance (ERS) was initiated during 2005 and updated in 2016 to direct surveillance efforts toward higher-value specimens by assigning points to different methods of encountering specimens for collection (strange-acting, roadkill, surveillance-trapped, etc.; specimen point values ranged from 1 to 15). We used the 2016–2019 data to re-evaluate the point values using a dynamic occupancy model. Additionally, we used ERS data from 2012–2015 and 2016–2019 to examine the impact that the point system had on surveillance data. Implementation of a point system increased positivity rates among specimens by 64%, indicating a substantial increase in the efficiency of the ERS to detect wildlife rabies. Our re-evaluation found that most points accurately reflect the value of the surveillance specimens. The notable exception was that samples from animals found dead were considerably more valuable for rabies detection than originally considered (original points = 5, new points = 20). This work demonstrates how specimen prioritization strategies can be used to refine and improve ERS in support of wildlife rabies management

Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4 + T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4 + T cell function at PND49. One potentially longlasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4 + T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4 + T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences

A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management