Participant Characteristics and Attendance Patterns for a Multispecialty Veterans Affairs ECHO Program 2012-2018.

Introduction: The Veteran Integrated Service Network (VISN) 20 Veterans Affairs-Extension for Community Healthcare Outcomes (VA-ECHO) program connects specialty and primary care providers (PCPs) across large geographic areas, utilizing video-teleconferencing with the intention of increasing access to care among underserved and isolated populations. No previously published work describes participation patterns of a multispecialty ECHO program. We describe the development of VISN 20 VA-ECHO program to inform the design and evaluation of ECHO programs. Methods: The participant cohort included VA-affiliated licensed health care professionals, including trainees, who attended at least one VISN 20 VA-ECHO session between April 2012 and December 2018. Participant characteristics reported include gender, clinical location, clinical specialty, discipline, and rurality. Results: Over the 6-year time frame, VISN 20 VA-ECHO offered 945 sessions in 14 clinical specialties and recorded 17,893 hours of attendance. The cohort included 1,346 participants, 74.3% of whom were female, 85.2% employed in medical centers, and 40.7% affiliated with primary care. Most participants (62.3%) attended one specialty exclusively; among all participants, 40% attended five or more sessions. Discussion: Although VA-ECHO was implemented to develop single specialty expertise among PCPs, our participant cohort represented a more diverse audience from a range of disciplines and specialties. Our experience may be valuable to other teams implementing ECHO programs. Conclusions: Through adaptability and strategies that actively promoted inclusion of a diverse audience, VISN 20 VA-ECHO expanded to include multiple clinical specialties and successfully engaged an audience across a large geographic area and beyond PCPs.

Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway.

HIV-associated nephropathy is characterized by renal podocyte proliferation and dedifferentiation. This study found that all-trans retinoic acid (atRA) reverses the effects of HIV-1 infection in podocytes. Treatment with atRA reduced cell proliferation rate by causing G1 arrest and restored the expression of the differentiation markers (synaptopodin, nephrin, podocin, and WT-1) in HIV-1-infected podocytes. It is interesting that both atRA and 9-cis RA increased intracellular cAMP levels in podocytes. Podocytes expressed most isoforms of retinoic acid receptors (RAR) and retinoid X receptors (RXR) with the exception of RXRgamma. RARalpha antagonists blocked atRA-induced cAMP production and its antiproliferative and prodifferentiation effects on podocytes, suggesting that RARalpha is required. For determination of the effect of increased intracellular cAMP on HIV-infected podocytes, cells were stimulated with either forskolin or 8-bromo-cAMP. Both compounds inhibited cell proliferation significantly and restored synaptopodin expression in HIV-infected podocytes. The effects of atRA were abolished by Rp-cAMP, an inhibitor of the cAMP/protein kinase A pathway and were enhanced by rolipram, an inhibitor of phosphodiesterase 4, suggesting that the antiproliferative and prodifferentiation effects of atRA on HIV-infected podocytes are cAMP dependent. Furthermore, both atRA and forskolin suppressed HIV-induced mitogen-activated protein kinase 1 and 2 and Stat3 phosphorylation. In vivo, atRA reduced proteinuria, cell proliferation, and glomerulosclerosis in HIV-1-transgenic mice. These findings suggest that atRA reverses the abnormal phenotype in HIV-1-infected podocytes by stimulating RARalpha-mediated intracellular cAMP production. These results demonstrate the mechanism by which atRA reverses the proliferation of podocytes that is induced by HIV-1.

ATRA induces podocyte differentiation and alters nephrin and podocin expression in vitro and in vivo.

BACKGROUND: Podocytes are terminally differentiated and highly specialized epithelial cells. The factors governing podocyte differentiation are poorly understood. We tested the hypothesis that all-trans retinoic acid (ATRA), a vitamin A derivative, induces podocyte differentiation in vitro and in vivo. METHODS: We tested the effects of ATRA on podocytes. Primary rat, primary mouse, and immortalized mouse podocytes were exposed to ATRA (1, 5, 10, 20, 40, 50, 80, 160, and 200 micromol/L) or control (ethanol) for 72 hours. Cell morphology was examined by electron microscopy, the expression of podocyte specific proteins was measured by immunoflourescence and Western blot analysis, cell number and apoptosis were measured by 3-[4,5] dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining, respectively. To determine if ATRA alters podocyte differentiation in vivo, experimental injury was induced in C57BL6 mice using the antiglomerular antibody. Animals were given either daily intraperitoneal ATRA (16 mg/kg) or vehicle (corn oil). For end points, we measured proteinuria, podocyte-specific protein immunostaining, and proliferation [proliferating cell nuclear antigen (PCNA)] at days 5 and 14 (N= 5/group/time point). RESULTS: ATRA induced podocyte process formation in vitro, and significantly increased the expression of nephrin and podocin. This coincided with a reduction in proliferation. ATRA also significantly prevented the decrease in staining for synaptopodin, nephrin, and podocin in experimental animals (P < 0.05 vs. control). This was accompanied by reduced proteinuria and decreased podocyte proliferation (P < 0.05 vs. control). CONCLUSION: ATRA induces podocyte differentiation in vitro and in vivo and alters the expression of certain podocyte-specific proteins. Further studies are ongoing to delineate the mechanism of this effect.