Keithmclaughlin0472

The Burkholderia pseudomallei phylogenetic cluster includes B. pseudomallei, B. mallei, B. thailandensis, B. oklahomensis, B. humptydooensis and B. singularis. Regarded as the only pathogenic members of this group, B. pseudomallei and B. mallei cause the diseases melioidosis and glanders, respectively. Additionally, variant strains of B. pseudomallei and B. thailandensis exist that include the geographically restricted B. pseudomallei that express a B. mallei-like BimA protein (BPBM), and B. thailandensis that express a B. pseudomallei-like capsular polysaccharide (BTCV). To establish a PCR-based assay for the detection of pathogenic Burkholderia species or their variants, five PCR primers were designed to amplify species-specific sequences within the bimA (Burkholderia intracellular motility A) gene. Our multiplex PCR assay could distinguish pathogenic B. pseudomallei and BPBM from the non-pathogenic B. thailandensis and the BTCV strains. A second singleplex PCR successfully discriminated the BTCV from B. thailandensis. Apart from B. humptydooensis, specificity testing against other Burkholderia spp., as well as other Gram-negative and Gram-positive bacteria produced a negative result. The detection limit of the multiplex PCR in soil samples artificially spiked with known quantities of B. pseudomallei and B. thailandensis were 5 and 6 CFU/g soil, respectively. Furthermore, comparison between standard bacterial culture and the multiplex PCR to detect B. pseudomallei from 34 soil samples, collected from an endemic area of melioidosis, showed high sensitivity and specificity. This robust, sensitive, and specific PCR assay will be a useful tool for epidemiological study of B. pseudomallei and closely related members with pathogenic potential in soil.

Limited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Dexketoprofen trometamol manufacturer Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease.

We isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously publishegs may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.

We are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.

Dengue fever is the most prevalent arboviral disease in the Brazilian Amazon and places a major health, social and economic burden on the region. Its association with deforestation is largely unknown, yet the clearing of tropical rainforests has been linked to the emergence of several infectious diseases, including yellow fever and malaria. This study aimed to explore potential drivers of dengue emergence in the Brazilian Amazon with a focus on deforestation.

An ecological study design using municipality-level secondary data from the Amazonas state between 2007 and 2017 (reported rural dengue cases, incremental deforestation, socioeconomic characteristics, healthcare and climate factors) was employed. Data were transformed according to the year with the most considerable deforestation. Associations were explored using bivariate analysis and a multivariate generalised linear model.

During the study period 2007-2017, both dengue incidence and deforestation increased. Bivariate analysis revealed increased vironmental effects on human health and to preserve the world's largest rainforest.

Previous research has shown that deforestation facilitates the emergence of vector-borne diseases. However, no significant dose-response relationships between dengue incidence and deforestation in the Brazilian Amazonas state were found in this study. The finding that access to healthcare was the only significant predictor of dengue incidence suggests that incidence may be more dependent on surveillance than transmission. Further research and public attention are needed to better understand environmental effects on human health and to preserve the world's largest rainforest.In recent years, machine learning methods have been applied to various prediction scenarios in time-series data. However, some processing procedures such as cross-validation (CV) that rearrange the order of the longitudinal data might ruin the seriality and lead to a potentially biased outcome. Regarding this issue, a recent study investigated how different types of CV methods influence the predictive errors in conventional time-series data. Here, we examine a more complex distributed lag nonlinear model (DLNM), which has been widely used to assess the cumulative impacts of past exposures on the current health outcome. This research extends the DLNM into an artificial neural network (ANN) and investigates how the ANN model reacts to various CV schemes that result in different predictive biases. We also propose a newly designed permutation ratio to evaluate the performance of the CV in the ANN. This ratio mimics the concept of the R-square in conventional statistical regression models. The results show that as the complexity of the ANN increases, the predicted outcome becomes more stable, and the bias shows a decreasing trend.