Improving annual albuminuria testing for individuals with diabetes.

BACKGROUND: Annual albuminuria screening detects the early stages of nephropathy in individuals with diabetes. Because early detection of albuminuria allows for interventions that lower the risk of developing chronic kidney disease, guidelines recommend annual testing for all individuals with type 2 diabetes mellitus and for those with type 1 diabetes for at least 5 years. However, at the Eskind Diabetes Clinic at the Vanderbilt University Medical Center, testing occurred less frequently than desired. METHODS: A quality improvement team first analysed the clinic's processes, identifying the lack of a systematic approach to testing as the likely cause for the low rate. The team then implemented two successive interventions in a pilot of patients seen by nurse practitioners in the clinic. In the first intervention, staff used a dashboard within the electronic health record while triaging each patient, pending an albuminuria order if testing had not been done within the past year. In the second intervention, clinic leadership sent daily reminders to the triage staff. A statistical process control chart tracked monthly testing rates. RESULTS: After 6 months, annual albuminuria testing increased from a baseline of 69% to 82%, with multiple special-cause signals in the control chart. CONCLUSIONS: This project demonstrates that a series of simple interventions can significantly impact annual albuminuria testing. This project's success likely hinged on using an existing workflow to systematically determine if a patient was due for testing and prompting the provider to sign a pended order for an albuminuria test. Other diabetes/endocrinology and primary care clinics can likely implement a similar process and so improve testing rates in other settings. When coupled with appropriate interventions to reduce the development of chronic kidney disease, such interventions would improve patient outcomes, in addition to better adhering to an established quality metric.

Cytotrophoblasts suppress macrophage-mediated inflammation through a contact-dependent mechanism.

PROBLEM: Gestational membrane (GM) infection provokes inflammation and can result in preterm prelabor rupture of membranes (PPROM). The choriodecidual layer of the GM includes decidual stromal cells (DSC), cytotrophoblasts (CTB), and macrophages (Mφ). Our laboratory has previously shown that DSCs suppress Mφ TNF-α production through secreted prostaglandin E2 . We hypothesized that CTBs would also inhibit Mφ cytokine expression through secreted mediators. METHOD OF STUDY: THP.1 Mφ-like cells with an NF-κB reporter construct or human blood monocyte-derived Mφ were co-cultured with the Jeg3 CTB cell line or primary human CTBs and challenged with group B streptococcus (GBS) or Toll-like receptor (TLR) agonists. Conditioned medium generated from CTB cultures was applied to Mφ cultures before infection or treatment. Alternatively, CTBs were co-incubated with, but physically separated from, Mφ and GBS or TLR-stimulated. NF-κB was assessed via alkaline phosphatase assay, and proinflammatory mediators were assessed by qRT-PCR and ELISA. RESULTS: CTBs suppressed GBS- or TLR-stimulated Mφ NF-κB activity, and TNF-α and MMP9 production. Direct physical contact between CTBs and Mφ was required for full immunosuppression. Immunosuppression could be overcome by increasing the ratio of Mφ to CTB. CONCLUSIONS: CTBs limit Mφ NF-κB activation and production of TNF-α and MMP9 through an as-yet unknown, cell-to-cell contact-mediated mechanism. This suppression is distinct from the PGE2 -mediated Mφ TNF-α suppression by DSC, suggesting that DSCs and CTBs regulate Mφ inflammation through distinct mechanisms. How Mφ integrates these signals in an intact GM will be paramount to determining causes and prevention of PPROM.

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.

Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition.