Integrated sensing and delivery of oxygen for next-generation smart wound dressings.

Chronic wounds affect over 6.5 million Americans and are notoriously difficult to treat. Suboptimal oxygenation of the wound bed is one of the most critical and treatable wound management factors, but existing oxygenation systems do not enable concurrent measurement and delivery of oxygen in a convenient wearable platform. Thus, we developed a low-cost alternative for continuous O2 delivery and sensing comprising of an inexpensive, paper-based, biocompatible, flexible platform for locally generating and measuring oxygen in a wound region. The platform takes advantage of recent developments in the fabrication of flexible microsystems including the incorporation of paper as a substrate and the use of a scalable manufacturing technology, inkjet printing. Here, we demonstrate the functionality of the oxygenation patch, capable of increasing oxygen concentration in a gel substrate by 13% (5 ppm) in 1 h. The platform is able to sense oxygen in a range of 5-26 ppm. In vivo studies demonstrate the biocompatibility of the patch and its ability to double or triple the oxygen level in the wound bed to clinically relevant levels.

Value of the first post-transplant biopsy for predicting long-term cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00-374.77; and 3.99, p = 0.005, 95% CI = 1.53-10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08-3.03; and 1.31, p = 0.001, 95% CI = 1.12-1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years). CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor.

Continuously-infused human C-reactive protein is neither proatherosclerotic nor proinflammatory in apolipoprotein E-deficient mice.

Studies of human native C-reactive protein (nCRP) in mice have shown effects ranging from proatherogenic, to antiatherogenic, to no effect. It is likely that these disparities are related to (a) the use, in some studies, of contaminated nCRP, or to (b) variation in CRP levels associated with either its episodic administration or the use of CRP-transgenic mice. In our study, 12-week-old male apolipoprotein E-deficient (apoE (-/-)) mice, maintained on a Western diet, received azide- and endotoxin-free nCRP (n = 23) or placebo (n = 23) continuously via osmotic pumps (20.4 microg/day) for 4 weeks. CRP-treated and control mice developed similar atherosclerotic lesions in whole aortas (nCRP: 10.4 +/- 4.7% vs. controls: 11.7 +/- 4.4%, P = 0.76) and aortic roots (nCRP: 65.0 +/- 7.8% vs. controls: 64.7 +/- 9.7%, P = 0.94). No differences were observed in macrophage or T-lymphocyte infiltrates and there was no meaningful change in VCAM-1 or IL-6 expression, in the levels of soluble VCAM-1, or in circulating proinflammatory (IL-1 beta, IL-6, IL-12p40, IL-12p70, TNF-alpha, and INF-gamma), or anti-inflammatory (IL-4 and IL-10) cytokines. We conclude that continuous infusion of uncontaminated nCRP in apoE (-/-) mice is not associated with increased atherosclerosis, does not alter systemic or local inflammation, and does not affect endothelial activation. These observations suggest that alternative approaches to study CRP (perhaps using different pentraxins in the mouse model or using a rabbit model instead of a mouse model) are needed to evaluate the effects of pentraxins on atherosclerosis.

Syncytiotrophoblast intercellular adhesion molecule-1 expression in placental villitis of unknown cause.

OBJECTIVE: The purpose of this study was to determine syncytiotrophoblast intercellular adhesion molecule-1 expression in villitis and in normal chorionic villi from term (37-42 weeks of gestation) placentas with or without villitis. STUDY DESIGN: A cross-sectional study was conducted to determine syncytiotrophoblast intercellular adhesion molecule-1 expression in villitis (n = 16) and in normal villi from placentas with or without villitis (n = 16). Villitis was diagnosed with antibodies to human leukocyte antigen-DR and CD3 and hematoxylin and eosin staining of serial sections; intercellular adhesion molecule-1 reactivity in syncytiotrophoblast was confirmed with antibodies to intercellular adhesion molecule-1 and cytokeratin. RESULTS: Villitis lesions had higher syncytiotrophoblast intercellular adhesion molecule-1 expression than normal chorionic villi from placentas with (19.9% vs 3.5% villi; P < .001) or without (19.9% vs 0.31% villi; P < .001) villitis. Normal villi from placentas with villitis had higher syncytiotrophoblast intercellular adhesion molecule-1 than villi from placentas without villitis (3.5% vs 0.31% villi; P < .001). CONCLUSION: Placentas with villitis have significantly more syncytiotrophoblast intercellular adhesion molecule-1 expression than placentas without villitis. The finding that normal villi from placentas with villitis have more syncytiotrophoblast intercellular adhesion molecule-1 than normal villi from placentas without villitis suggests that syncytiotrophoblast intercellular adhesion molecule-1 could be the first step in villitis development.