Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n ≈ 24 per dose per compound) were exposed to test compounds (0.4–120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system

Dyadic Digital Health Interventions: Their Rationale and Implementation

While most psychosocial and behavioral digital health interventions have been designed to be consumed by an individual, intervening at the level of a dyad – two interdependent individuals – can more comprehensively address the needs of both individuals and their relationship. The clinical utility of the dyadic digital health intervention approach, as well as the practical implementation of this design, will be demonstrated via three examples: eSCCIP, FAMS, and OurRelationship

Water-Use Data in the United States: Challenges and Future Directions

In the United States, greater attention has been given to developing water supplies and quantifying available waters than determining who uses water, how much they withdraw and consume, and how and where water use occurs. As water supplies are stressed due to an increasingly variable climate, changing land-use, and growing water needs, greater consideration of the demand side of the water balance equation is essential. Data about the spatial and temporal aspects of water use for different purposes are now critical to long-term water supply planning and resource management. We detail the current state of water-use data, the major stakeholders involved in their collection and applications, and the challenges in obtaining high-quality nationally consistent data applicable to a range of scales and purposes. Opportunities to improve access, use, and sharing of water-use data are outlined. We cast a vision for a world-class national water-use data product that is accessible, timely, and spatially detailed. Our vision will leverage the strengths of existing local, state, and federal agencies to facilitate rapid and informed decision-making, modeling, and science for water resources. To inform future decision-making regarding water supplies and uses, we must coordinate efforts to substantially improve our capacity to collect, model, and disseminate water-use data

HIV-1 protease inhibitors and clinical malaria: A secondary analysis of the AIDS Clinical Trials Group A5208 study

HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted. Copyrigh

Community engagement practices at research centers in U.S. minority institutions: Priority populations and innovative approaches to advancing health disparities research

This paper details U.S. Research Centers in Minority Institutions (RCMI) Community Engagement Cores (CECs): (1) unique and cross-cutting components, focus areas, specific aims, and target populations; and (2) approaches utilized to build or sustain trust towards community participation in research. A mixed-method data collection approach was employed for this cross-sectional study of current or previously funded RCMIs. A total of 18 of the 25 institutions spanning 13 U.S. states and territories participated. CEC specific aims were to support community engaged research (94%); to translate and disseminate research findings (88%); to develop partnerships (82%); and to build capacity around community research (71%). Four open-ended questions, qualitative analysis, and comparison of the categories led to the emergence of two supporting themes: (1) establishing trust between the community-academic collaborators and within the community and (2) building collaborative relationships. An overarching theme, building community together through trust and meaningful collaborations, emerged from the supporting themes and subthemes. The RCMI institutions and their CECs serve as models to circumvent the historical and current challenges to research in communities disproportionately affected by health disparities. Lessons learned from these cores may help other institutions who want to build community trust in and capacities for research that addresses community-related health concerns

Genome-wide association Scan of dental caries in the permanent dentition

Background: Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults. Methods: Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries. Results: Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens. Conclusions: As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment

Tracking of unpredictable moving stimuli by pigeons

Despite being observed throughout the animal kingdom, catching a moving object is a complex task and little is known about the mechanisms that underlie this behavior in non-human animals. Three experiments examined the role of prediction in capture of a moving object by pigeons. In Experiment 1, a stimulus moved in a linear trajectory, but sometimes made an unexpected 90o turn. The sudden turn had only a modest effect on capture and error location, and the analyses suggested that the birds had adjusted their tracking to the novel motion. In Experiment 2, the role of visual input during a turn was tested by inserting disappearances (either 1.5 cm or 4.5 cm) on both the straight and turn trials. The addition of the disappearance had little effect on capture success, but delayed capture location with the larger disappearance leading to greater delay. Error analyses indicated that the birds adapted to the post-turn, post-disappearance motion. Experiment 3 tested the role of visual input when the motion disappeared behind an occluder and emerged in either a straight line or at a 90o angle. The occluder produced a disruption in capture success but did not delay capture. Error analyses indicated that the birds did not adjust their tracking to the new motion on turn trials following occlusion. The combined results indicate that pigeons can anticipate the future position of a stimulus, and can adapt to sudden, unpredictable changes in motion but do so better after a disappearance than after an occlusion

The Frequency of Malaria Is Similar among Women Receiving either Lopinavir/Ritonavir or Nevirapine-based Antiretroviral Treatment

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population

SBML Level 3: an extensible format for the exchange and reuse of biological models

Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution