Using a large-scale reference resource, we show that the tissue-anchored model provides a transcriptome-based approach to predicting the primary affected tissue of developmental disorders. Using gradient boosted regression trees to model evolutionary rate under a range of model parameters, selected features explain up to 62% of the variation in evolutionary rate and provide additional support for the tissue model. Finally, we investigate several methodological implications, including the importance of evolutionary-rate-aware gene expression imputation models using genetic data for improved search for disease-associated genes in transcriptome-wide association studies. Collectively, this study presents a comprehensive transcriptome-based analysis of a range of factors that may constrain molecular evolution and proposes a novel framework for the study of gene function and disease mechanism.

Saliva contains a very complex mixture of proteins for defense against microbiological pathogens and for oral food perception. Howler monkeys are Neotropical primates that can consume a mostly leaf diet. They are well known to thrive in highly disturbed habitats where they may cope with a diversity of dietary challenges and infection risks. We aimed to describe the salivary proteome of howlers to contribute to better understanding of their physiology.

We analyzed the salivary proteins of wild black howler monkeys (

), by SDS-PAGE-1-D and Nano LC-MS/MS and categorized them by their function involved in host defense and oral food perception.

Our proteomic analysis identified 156 proteins in howler saliva including a number of host defense peptides that are the first line of defense in mammals, such as defensin, cathelicidin, dermcidin, and lactotransferrin, and proteins with anti-bacterial, anti-fungal, and anti-viral capacity, such as IgA, IgG, IgM, BPI, salivary heat shock 70 kDa protein, beta-2-microb proteins necessary for taste perception, including salivary carbonic anhydrase VI, cystatin D, IgA, and fatty acid-binding protein. Proteins to detect astringent foods were identifying, including four members of cystatins (A, B, C and D), lactoperoxidase, and histidine-rich proteins. No chitinase and amylase were identified as would be expected because howlers do not eat insects and little starch. These findings provide basic information to future studies in oral biology, ingestive physiology, and physiological ecology of mammals and non-human primates.

The high burden of infectious disease and associated antimicrobial use likely contribute to the emergence of antimicrobial resistance in remote Australian Aboriginal communities. We aimed to develop and apply context-specific tools to audit antimicrobial use in the remote primary healthcare setting.

We adapted the General Practice version of the National Antimicrobial Prescribing Survey (GP NAPS) tool to audit antimicrobial use over 2-3 weeks in 15 remote primary healthcare clinics across the Kimberley region of Western Australia (03/2018-06/2018), Top End of the Northern Territory (08/2017-09/2017) and far north Queensland (05/2018-06/2018). At each clinic we reviewed consecutive clinic presentations until 30 presentations where antimicrobials had been used were included in the audit. Data recorded included the antimicrobials used, indications and treating health professional. We assessed the appropriateness of antimicrobial use and functionality of the tool.

We audited the use of 668 antimicrobials. Skin and soft tissue infections were the dominant treatment indications (WA 35%; NT 29%; QLD 40%). Compared with other settings in Australia, narrow spectrum antimicrobials like benzathine benzylpenicillin were commonly given and the appropriateness of use was high (WA 91%; NT 82%; QLD 65%). While the audit was informative, non-integration with practice software made the process manually intensive.

Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems.

Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems.

The Worldwide Hydrobiogeochemistry Observation Network for Dynamic River Systems (WHONDRS) is a consortium that aims to understand complex hydrologic, biogeochemical, and microbial connections within river corridors experiencing perturbations such as dam operations, floods, and droughts. For one ongoing WHONDRS sampling campaign, surface water metabolite and microbiome samples are collected through a global survey to generate knowledge across diverse river corridors. Apitolisib clinical trial Metabolomics analysis and a suite of geochemical analyses have been performed for collected samples through the Environmental Molecular Sciences Laboratory (EMSL). The obtained knowledge and data package inform mechanistic and data-driven models to enhance predictions of outcomes of hydrologic perturbations and watershed function, one of the most critical components in model-data integration. To support efforts of the multi-domain integration and make the ever-growing data package more accessible for researchers across the world, a Shiny/R Grapamic user interface, the WHONDRS-GUI has functionality for searching, compiling, integrating, visualizing and exporting different data types that can easily be used by the community. The web application and data package are available at https//data.ess-dive.lbl.gov/view/doi10.15485/1484811, which enables users to simultaneously obtain access to the data and code and to subsequently run the web app locally. The WHONDRS-GUI is also available for online use at Shiny Server (https//xmlin.shinyapps.io/whondrs/).

Uganda has successfully reduced pediatric HIV infections through prevention of mother-to-child transmission of HIV (PMTCT) programs, yet little is known about adherence to infant-specific components of interventions. We hypothesized that infants born to mothers receiving the WiseMama (WM) electronic drug monitoring (EDM)-based adherence intervention would have increased uptake of six-week post-natal nevirapine (NVP) infant prophylaxis and better adherence to six-week early infant diagnosis (EID) HIV testing.

At two sites in Uganda, the Wise Infant Study (WIN) prospectively followed an infant cohort. Infants were born to women enrolled in an RCT testing the effect of real-time reminders delivered via EDM on maternal adherence to antiretroviral therapy. We assessed intrapartum and discharge receipt of NVP prophylaxis using pharmacy and infant HIV DNA testing laboratory data.

Of 121 women eligible for WIN, 97 (80%) consented and enrolled; 46 had been randomized to control and 51 to intervention. There were no differences in receipt of a six-week NVP supply (control 87%, intervention 82%, p = 0.