Prevalence of antibody to Trypanosoma cruzi in Hispanic-surnamed patients seen at Parkland Health & Hospital System, Dallas, Texas

<p>Abstract</p> <p>Background</p> <p>Chagas disease constitutes an important public health threat in terms of morbidity and mortality in the areas in the United States where immigrant populations from Latin America are conspicuous. We conducted a survey to assess the prevalence of anti-<it>T. cruzi </it>antibody in Hispanic-surnamed patients seen at Parkland Memorial Hospital in Dallas, Texas.</p> <p>Findings</p> <p>Five hundred serum specimens from Hispanic-surnamed patients were tested by a preliminary ELISA method. On a subset of 50 sera confirmatory testing was also performed using an alternative ELISA, indirect immunofluorescence, and TESA immunoblot. For 274 of 500 Hispanic-surnamed patients, we were able to ascertain immigration status upon medical chart review. Of the 274 sera analyzed, one sample tested as positive for anti-<it>T. cruzi </it>antibody by the preliminary ELISA, and by the three confirmatory methods.</p> <p>Conclusions</p> <p>The goal of this study is to increase the awareness of <it>T. cruzi </it>infection and Chagas disease in areas where the Latin American immigrant communities are growing. Our study highlights the importance of testing for Chagas disease in the populations most at risk, and the need for current data on the actual seroprevalence in areas where such immigrant populations are conspicuous. Larger-scale epidemiologic surveys on Chagas disease in the immigrant communities from Latin America are warranted.</p

Differential neural mechanisms for early and late prediction error detection

Emerging evidence indicates that prediction, instantiated at different perceptual levels, facilitate visual processing and enable prompt and appropriate reactions. Until now, the mechanisms underlying the effect of predictive coding at different stages of visual processing have still remained unclear. Here, we aimed to investigate early and late processing of spatial prediction violation by performing combined recordings of saccadic eye movements and fast event-related fMRI during a continuous visual detection task. Psychophysical reverse correlation analysis revealed that the degree of mismatch between current perceptual input and prior expectations is mainly processed at late rather than early stage, which is instead responsible for fast but general prediction error detection. Furthermore, our results suggest that conscious late detection of deviant stimuli is elicited by the assessment of prediction error’s extent more than by prediction error per se. Functional MRI and functional connectivity data analyses indicated that higher-level brain systems interactions modulate conscious detection of prediction error through top-down processes for the analysis of its representational content, and possibly regulate subsequent adaptation of predictivemodels. Overall, our experimental paradigm allowed to dissect explicit from implicit behavioral and neural responses to deviant stimuli in terms of their reliance on predictive models

Effects of the Indianapolis Vocational Intervention Program (IVIP) on defeatist beliefs, work motivation, and work outcomes in serious mental illness

Defeatist beliefs and amotivation are prominent obstacles in vocational rehabilitation for people with serious mental illnesses (SMI). The CBT-based Indianapolis Vocational Intervention Program (IVIP) was specifically designed to reduce defeatist beliefs related to work functioning. In the current study, we examined the impact of IVIP on defeatist beliefs and motivation for work, hypothesizing that IVIP would be associated with a reduction in defeatist beliefs and greater motivation for work. We also examined the effects of IVIP on these variables as well as work outcomes during a 12-month follow-up. Participants with SMI (n=64) enrolled in a four-month work therapy program were randomized to IVIP or a support therapy group (SG). Assessments were conducted at baseline, post-treatment (4months), and follow-up (1year). Compared to those in SG condition, individuals randomized to IVIP condition reported greater reductions in defeatist beliefs and greater motivation for work at follow-up, along with greater supported employment retention rates. Specifically treating and targeting negative expectations for work therapy improves outcomes, even once active supports of the IVIP program and work therapy are withdrawn

Primers for Castilleja and their Utility Across Orobanchaceae: II. Single‐copy nuclear loci

Premise of the study: We developed primers targeting nuclear loci in Castilleja with the goal of reconstructing the evolutionary history of this challenging clade. These primers were tested across other major clades in Orobanchaceae to assess their broader utility.Methods and Results: We assembled low-coverage genomes for three taxa in Castilleja and developed primer combinations for the single-copy conserved ortholog set (COSII) and the pentatricopeptide repeat (PPR) gene family. These primer combinations were designed to take advantage of the Fluidigm microfluidic PCR platform and are well suited for high-throughput sequencing applications. Eighty-seven primers were designed for Castilleja, and 27 were found to have broader utility in Orobanchaceae.Conclusions: These results demonstrate the utility of these primers, not only across Castilleja, but for other lineages within Orobanchaceae as well. This expanded molecular toolkit will be an asset to future phylogenetic studies in Castilleja and throughout Orobanchaceae

Ecological impact assessments fail to reduce risk of bat casualties at wind farms

Demand for renewable energy is rising exponentially. While this has benefits in reducing greenhouse gas emissions, there may be costs to biodiversity [1]. Environmental Impact Assessments (EIAs) are the main tool used across the world to predict the overall positive and negative effects of renewable energy developments before planning consent is given, and the Ecological Impact Assessments (EcIAs) within them assess their species-specific effects. Given that EIAs are undertaken globally, are extremely expensive, and are enshrined in legislation, their place in evidence-based decision making deserves evaluation. Here we assess how well EIAs of wind-farm developments protect bats. We found they do not predict the risks to bats accurately, and even in those cases where high risk was correctly identified, the mitigation deployed did not avert the risk. Given that the primary purpose of an EIA is to make planning decisions evidence-based, our results indicate that EIA mitigation strategies used to date have been ineffective in protecting bats. In the future, greater emphasis should be placed on assessing the actual impacts post-construction and on developing effective mitigation strategies

Inhibition of HIV-1 gene expression by Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A

<p>Abstract</p> <p>Background</p> <p>Eukaryotic translation initiation factor eIF5A has been implicated in HIV-1 replication. This protein contains the apparently unique amino acid hypusine that is formed by the post-translational modification of a lysine residue catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase (DOHH). DOHH activity is inhibited by two clinically used drugs, the topical fungicide ciclopirox and the systemic medicinal iron chelator deferiprone. Deferiprone has been reported to inhibit HIV-1 replication in tissue culture.</p> <p>Results</p> <p>Ciclopirox and deferiprone blocked HIV-1 replication in PBMCs. To examine the underlying mechanisms, we investigated the action of the drugs on eIF5A modification and HIV-1 gene expression in model systems. At early times after drug exposure, both drugs inhibited substrate binding to DOHH and prevented the formation of mature eIF5A. Viral gene expression from HIV-1 molecular clones was suppressed at the RNA level independently of all viral genes. The inhibition was specific for the viral promoter and occurred at the level of HIV-1 transcription initiation. Partial knockdown of eIF5A-1 by siRNA led to inhibition of HIV-1 gene expression that was non-additive with drug action. These data support the importance of eIF5A and hypusine formation in HIV-1 gene expression.</p> <p>Conclusion</p> <p>At clinically relevant concentrations, two widely used drugs blocked HIV-1 replication <it>ex vivo</it>. They specifically inhibited expression from the HIV-1 promoter at the level of transcription initiation. Both drugs interfered with the hydroxylation step in the hypusine modification of eIF5A. These results have profound implications for the potential therapeutic use of these drugs as antiretrovirals and for the development of optimized analogs.</p

Prevention of incipient carious lesions with various interventions during fixed and removable orthodontic treatment. A systematic review and meta-analysis

Objective: To systematically review and quantify the effectiveness of interventions in reducing caries development during orthodontic treatment and evaluate the quality of evidence for the development of clinical guidelines. Materials and methods: A comprehensive literature search of the Cochrane, EMBASE and MEDLINE databases was conducted to identify eligible randomised controlled trials (RCTs). The risk of bias was assessed using the Cochrane risk of bias (RoB 2) tool. In order to facilitate the development of clinical guidelines, the quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: A total of 18 RCTs were included in the qualitative synthesis, of which 10 had a high risk of bias, and eight had minor concerns. Three RCTs that investigated the efficacy of fluoride interventions during fixed orthodontic treatment were included in the quantitative synthesis. The pooled effect size resulted in a risk reduction of 0.23 (95% CI:-0.35,-0.11, p < 0.001) in the intervention group compared to controls. The GRADE evaluation identified the evidence as moderate due to the limited number of RCTs and moderate heterogeneity (I-squared statistic of 49.3%). Conclusions: Although fluoride is the most effective evidence-based preventive intervention during orthodontic treatment, large RCTs are required to provide high quality evidence. Further studies are needed to evaluate the caries preventive effects of oral hygiene programs, chlorhexidine, CPP-ACP and other interventions

In Vivo Turnover of Tau and APP Metabolites in the Brains of Wild-Type and Tg2576 Mice: Greater Stability of sAPP in the β-Amyloid Depositing Mice

The metabolism of the amyloid precursor protein (APP) and tau are central to the pathobiology of Alzheimer's disease (AD). We have examined the in vivo turnover of APP, secreted APP (sAPP), Aβ and tau in the wild-type and Tg2576 mouse brain using cycloheximide to block protein synthesis. In spite of overexpression of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain more slowly, particularly in the Tg2576 model where the half-life of both the endogenous murine and transgene-derived human sAPP is nearly doubled compared to wild-type mice. The important Aβ degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Aβ40 and Aβ42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. The cytoskeletal-associated protein tau was found to be highly stable in both wild-type and Tg2576 mice. Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a β-amyloid depositing, APP overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the β-amyloid depositing Tg2576 mice may represent a neuroprotective response