Biochemical and Hematologic Reference Intervals for Anesthetized, Female, Juvenile Yorkshire Swine.

Swine are widely used in biomedical research, translational research, xenotransplantation, and agriculture. For these uses, physiologic reference intervals are extremely important for assessing the health status of the swine and diagnosing disease. However, few biochemical and hematologic reference intervals that comply with guidelines from the Clinical and Laboratory Standards Institute and the American Society for Veterinary Clinical Pathology are available for swine. These guidelines state that reference intervals should be determined by using 120 subjects or more. The aim of this study was to generate hematologic and biochemical reference intervals for female, juvenile Yorkshire swine (Sus scrofa domesticus) and to compare these values with those for humans and baboons (Papio hamadryas). Blood samples were collected from the femoral artery or vein of female, juvenile Yorkshire swine, and standard hematologic and biochemical parameters were analyzed in multiple studies. Hematologic and biochemical reference intervals were calculated for arterial blood samples from Yorkshire swine (n = 121 to 124); human and baboon reference intervals were obtained from the literature. Arterial reference intervals for Yorkshire swine differed significantly from those for humans and baboons in all commonly measured parameters except platelet count, which did not differ significantly from the human value, and glucose, which was not significantly different from the baboon value. These data provide valuable information for investigators using female, juvenile Yorkshire swine for biomedical re- search, as disease models, and in xenotransplantation studies as well as useful physiologic information for veterinarians and livestock producers. Our findings highlight the need for caution when comparing data and study outcomes between species.

Rapid Coating Process Generates Omniphobic Dentures in Minutes to Reduce C. albicans Biofouling.

Localized infections caused by biofilm formation on dentures pose a serious health risk for patients, especially the elderly, as they can lead to complications such as pneumonia. Daily enzymatic denture cleaners do not fully prevent biofilm formation on dentures. Here we developed a rapid coating process to apply a liquid repellent surface to dentures in ∼5 min and demonstrated a significant 225-fold reduction of Candida albicans adhesion over 6 days, compared to uncoated dentures. This rapid coating process could be applied to dentures and other dental devices chair-side and allow the research community to quickly and easily generate ominphobic surfaces.

Systematic morphological profiling of human gene and allele function via Cell Painting.

We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters. This unbiased morphologic map of gene function revealed TRAF2/c-REL negative regulation of YAP1/WWTR1-responsive pathways. We confirmed this discovery of functional connectivity between the NF-κB pathway and Hippo pathway effectors at the transcriptional level, thereby expanding knowledge of these two signaling pathways that critically regulate tumor initiation and progression. We make the images and raw data publicly available, providing an initial morphological map of major biological pathways for future study.

A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling.

Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.

An extracorporeal blood-cleansing device for sepsis therapy.

Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.