The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/ 100 cm 2 ; n ‫؍‬ 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm 2 ). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm 2 ; n ‫؍‬ 2714 objects) compared to the controls (2,674 CFU/100 cm 2 ; n ‫؍‬ 2,831 objects [P < 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.

The proteoglycan versican is essential to the formation of endocardial cushion mesenchyme by epithelial-mesenchymal transformation (EMT). A potentially important factor in the regulation of versican activity during cushion EMT is proteolysis by ADAMTS metalloproteinases. Using antibodies to the DPEAAE neoepitope created by ADAMTS proteolysis of versican, we detected the amino terminal 70-kDa versican cleavage fragment in cardiac cushions. Initially (i.e., 9.5 days post coitum [dpc]), the fragment is associated with endocardial cells undergoing EMT and with newly derived mesenchymal cells. ADAMTS-1 and its cofactor fibulin-1 were also associated with these cells. As cushions become increasingly populated with mesenchymal cells (10.5-12.5 dpc), the fragment remains asymmetrically distributed compared with the pattern of total versican. Highest levels of the fragment are present in regions immediately subjacent to the endocardium characterized as having densely packed, rounded cells, lacking cellular protrusions. With further development (i.e., 12.5-14.5 dpc), the pattern of fragment distribution within cushions broadens to include the ECM surrounding loosely packed mesenchymal cells in the cushion core. Together, the findings reveal that versican proteolysis leading to the production of the 70-kDa fragment is integral to the formation and differentiation of endocardial cushion mesenchyme.

Cleaning is an effective way to lower the bacterial burden (BB) on surfaces and minimize the infection risk to patients. However, BB can quickly return. Copper, when used to surface hospital bed rails, was found to consistently limit surface BB before and after cleaning through its continuous antimicrobial activity.

An important phase of cardiac outflow tract (OFT) formation is the remodeling of the distal region of the common outlet in which the myocardial sleeve is replaced by with smooth muscle. Here we demonstrate that expression of the proteoglycan versican is reduced before the loss of myocardium from the distal cardiac outlet concomitant with an increase in production of the N-terminal cleavage fragment of versican. To test whether versican proteolysis plays a role in OFT remodeling, we determined the effects of adenoviral-mediated expression of a versican isoform devoid of known matrix metalloproteinase cleavage sites (V3) and an N-terminal fragment of versican (G1). V3 expression promoted an increase in thickness of the proximal OFT myocardial layer independent of proliferation. In contrast, the G1 domain caused thinning and interruptions of the OFT myocardium. These in vivo findings were consistent with findings using cultured primary cardiomyocytes showing that the V3 promoted myocardial cell-cell association while the G1 domain caused a loss of myocardial cell-cell association. Taken together, we conclude that intact versican and G1-containing versican cleavage products have opposing effects on myocardial cells and that versican proteolysis may facilitate the loss of distal myocardium during OFT remodeling.

We report the consistent distribution of a population of pigmented trp-1-positive cells in several important septal and valvular structures of the normal mouse (C57BL/6) heart. The pigmented cell population was first apparent by E16.5 p.c. in the right atrial wall and extended into the atrium along the interatrial septum. By E17.5, these cells were found along the apical membranous interventricular septum near or below the surface of the endocardium. The most striking distribution of dark pigmented cells was found in the tricuspid and mitral valvular leaflets and chordae tendineae. The normal distribution of pigmented cells in the valvuloseptal apparatus of C57BL/6 adult heart suggests that a premelanocytic lineage may participate in the earlier morphogenesis of the valve leaflets and chordae tendineae. The origin of the premelanocyte lineage is currently unknown. The most likely candidate populations include the neural crest and the epicardially derived cells. The only cell type in the heart previously shown to form melanocytes is the neural crest. The presence of neural crest cells, but not melanocytes, in some of the regions we describe has been reported by others. However, previous reports have not shown a contribution of melanocytes or neural crest derivatives to the atrioventricular valve leaflets or chordae tendineae in mouse hearts. If these cells are of neural crest origin, it would suggest a possibly greater contribution and persistence of neural crest cells to the valvuloseptal apparatus than has been previously understood.