Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin

The recruitment of monocytes from the bloodstream is crucial in the accumulation of macrophages and dendritic cells in type 1 diabetic pancreases. Adhesion via integrins to endothelium and extracellular matrix proteins, such as fibronectin (FN), and the production of myeloid-related protein (MRP)-8, -14, and -8/14 by recently transmigrated monocytes are thought to be instrumental in such recruitment. We determined the FN-adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients and related them to the subjects' serum levels of MRP-8, -14 and -8/14. Monocytes of type 1 diabetic patients displayed an increased adhesion to fibronectin in comparison with type 2 patients and healthy control subjects but had a normal expression of the FN binding integrins CD29, CD49a, CD49d, and CD49e (although CD11b and CD18 expression was increased). MRP-8/14, which was increased in the sera of type 1 diabetic patients, induced healthy donor monocytes to adhere to FN and upregulate CD11b expression in a dosage-dependent manner. The observed MRP-induced increased adhesion of monocytes to FN and upregulation of CD11b most likely contributed to a facilitated accumulation of monocytes and monocyte-derived cells at the site of inflammation, in this case the pancreatic islets

Tele-education model for primary care providers to advance diabetes equity: Findings from Project ECHO Diabetes

IntroductionIn the US, many individuals with diabetes do not have consistent access to endocrinologists and therefore rely on primary care providers (PCPs) for their diabetes management. Project ECHO (Extension for Community Healthcare Outcomes) Diabetes, a tele-education model, was developed to empower PCPs to independently manage diabetes, including education on diabetes technology initiation and use, to bridge disparities in diabetes.MethodsPCPs (n=116) who participated in Project ECHO Diabetes and completed pre- and post-intervention surveys were included in this analysis. The survey was administered in California and Florida to participating PCPs via REDCap and paper surveys. This survey aimed to evaluate practice demographics, protocols with adult and pediatric T1D management, challenges, resources, and provider knowledge and confidence in diabetes management. Differences and statistical significance in pre- and post-intervention responses were evaluated via McNemar’s tests.ResultsPCPs reported improvement in all domains of diabetes education and management. From baseline, PCPs reported improvement in their confidence to serve as the T1D provider for their community (pre vs post: 43.8% vs 68.8%, p=0.005), manage insulin therapy (pre vs post: 62.8% vs 84.3%, p=0.002), and identify symptoms of diabetes distress (pre vs post: 62.8% vs 84.3%, p=0.002) post-intervention. Compared to pre-intervention, providers reported significant improvement in their confidence in all aspects of diabetes technology including prescribing technology (41.2% vs 68.6%, p=0.001), managing insulin pumps (41.2% vs 68.6%, p=0.001) and hybrid closed loop (10.2% vs 26.5%, p=0.033), and interpreting sensor data (41.2% vs 68.6%, p=0.001) post-intervention.DiscussionPCPs who participated in Project ECHO Diabetes reported increased confidence in diabetes management, with notable improvement in their ability to prescribe, manage, and troubleshoot diabetes technology. These data support the use of tele-education of PCPs to increase confidence in diabetes technology management as a feasible strategy to advance equity in diabetes management and outcomes

Listeria pathogenesis and molecular virulence determinants

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research