Long-term treatment outcomes in a First Nations high school population with opioid use disorder.

OBJECTIVE: To assess for long-term positive effects of buprenorphine treatment (BT) on opioid use disorder (OUD) at a Nishnawbe Aski Nation high school clinic. DESIGN: Postgraduation telephone survey of high school students between March 2017 and January 2018. SETTING: Dennis Franklin Cromarty High School in Thunder Bay, Ont. PARTICIPANTS: All 44 students who had received BT in the high school clinic during its operation from 2011 to 2013 were eligible to participate. MAIN OUTCOME MEASURES: Current substance use, BT status, and social and employment status. RESULTS: Thirty-eight of the 44 students who had received BT in the high school clinic were located and approached; 32 consented to participate in the survey. A descriptive analysis of the surveyed indicators was undertaken. Almost two-thirds (n = 20, 62.5%) of the cohort had graduated from high school, more than one-third (n = 12, 37.5%) were employed full time, and most (n = 29, 90.6%) rated their health as "good" or "OK." A greater percentage of participants who continued taking BT after high school (n = 19, 61.3%) were employed full time (n = 8, 42.1% vs n = 4, 33.3%) and were abstinent from alcohol (n = 12, 63.2% vs n = 4, 33.3%). Participants still taking BT were significantly more likely to have obtained addiction counseling in the past year than those participants not in treatment (n = 9, 47.4% vs n = 1, 8.3%; P = .0464). CONCLUSION: The study results suggest that offering OUD treatment to youth in the form of BT in a high school clinic might be an effective strategy for promoting positive long-term health and social outcomes. Clinical treatment guidelines currently recommend long-term opioid agonist treatment as the treatment of choice for OUD in the general population; they should consider adding youth to the population that might also benefit.

CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.

α1ß1 integrin-mediated adhesion inhibits macrophage exit from a peripheral inflammatory lesion.

Integrins are adhesion molecules critical for the recruitment of leukocytes from blood into peripheral tissues. However, whether integrins are also involved in leukocyte exit from peripheral tissues via afferent lymphatics to the draining lymph node remains poorly understood. In this article, we show that adhesion by the collagen IV-binding integrin α1ß1 unexpectedly inhibited macrophage exit from inflamed skin. We monitored macrophages exiting mouse footpads using a newly developed in situ pulse labeling technique. Blockade of α1ß1 integrin or genetic deletion (Itga1(-/-)) increased macrophage exit efficiency. Chemotaxis assays through collagen IV showed more efficient migration of Itga1(-/-) macrophages relative to wild type. Given that macrophages are key orchestrators of inflammation, α1ß1 integrin adhesion may represent a mechanism for regulating inflammatory responses by controlling macrophage exit or persistence in inflamed tissues.

Actin polymerization stabilizes α4ß1 integrin anchors that mediate monocyte adhesion.

Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upstream α4ß1 integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron microscopy revealed that this culminates in the formation of structures that anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell deformation, displacement, and detachment. Transfection of dominant-negative constructs and inhibition of function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces.

Endophthalmitis post complicated cataract surgery associated with Klebsiella pneumoniae.

An 82-year-old woman underwent complicated cataract surgery with subsequent endophthalmitis. She presented with a unique purulent collection with ciliary body involvement and Klebsiella pneumoniae was grown on culture. Klebsiella is a rare cause of endophthalmitis and ciliary body involvement has not previously been reported.

Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE.

Models of inflammatory and immune diseases are extensively studied in mice with engineered genetic mutations, and tracking the recruitment of blood leukocytes into tissues is an important component of these studies. A direct in situ method for labeling the total pool of blood cells in mice by a single intravenous injection of the fluorescent dye CFDA SE (CFSE) is described. The fluorescence intensity of labeled cells initially declines, but remains stable after 4 h, enabling detection weeks after labeling. Labeled leukocytes can be tracked as they accumulate in lymphoid tissues and sites of inflammation and then be immunophenotyped for analysis by flow cytometry. This method is rapid, reproducible and simple to perform.