Study of the Structure of Hyperbranched Polyglycerol Coatings and Their Antibiofouling and Antithrombotic Applications

While blood‐contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma‐grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG‐coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation

Uranium mobility in organic matter-rich sediments: A review of geological and geochemical processes

Uranium (U) is of enormous global importance because of its use in energy generation, albeit with potential environmental legacies. While naturally occurring U is widespread in the Earth's crust at concentrations of ~1 to 3 ppm, higher concentrations can be found, includingwithin organicmatter (OM)-rich sediments, leading to economic extraction opportunities. The primary determinants of U behaviour in ore systems are pH, Eh, U oxidation state (U(IV), U(VI)) and the abundance of CO3 2– ions. The concentration/availability and interrelationships among such determinants vary, and the solubility and mobility of ions (e.g. OH-, CO3 2–, PO4 3-, SiO4 4-, SO4 2-) that compete for U (primarily as U(VI)) will also influence the mobility of U. In addition, the presence of OM can influence U mobility and fate by the degree of OMsorption to mineral surfaces (e.g. Fe- and Si- oxides and hydroxides). Within solid-phase OM, microbes can influence U oxidation state and U stability through direct enzymatic reduction, biosorption, biomineralisation and bioaccumulation. The biogenic UO2 product is, however, reported to be readily susceptible to reoxidation and therefore more likely remobilised over longer time periods. Thus several areas of uncertainty remain with respect to factors contributing to U accumulation, stability and/or (re)mobilisation. To address these uncertainties, this paper reviews U dynamics at both geological and molecular scales. Here we identify U-OMbond values that are in agreement, relatively strong, independent from ionic strength and which may facilitate either U mobilisation or immobilisation, depending on environmental conditions. We also examine knowledge gaps in the literature, with U-OM solubility data generally lacking in comparison to data for U sorption and dissolution, and little information available on multi-component relationships, such as UOM-V (V as vanadate). Furthermore, the capability ofOMto influence the oxidation state of U at near surface conditions remains unclear, as it can be postulated that electron shuttling by OM may contribute to changes in U redox state otherwise mediated by bacteria. Geochemical modelling of the environmental mobility of U will require incorporation of data from multi-corporation studies, as well as from studies of U-OM microbial interactions, all of which are considered in this review

Pathology and Pathogenesis of Brain Lesions Produced by Clostridium perfringens Type D Epsilon Toxin.

Clostridium perfringens type D epsilon toxin (ETX) produces severe, and frequently fatal, neurologic disease in ruminant livestock. The disorder is of worldwide distribution and, although vaccination has reduced its prevalence, ETX still causes substantial economic loss in livestock enterprises. The toxin is produced in the intestine as a relatively inactive prototoxin, which is subsequently fully enzymatically activated to ETX. When changed conditions in the intestinal milieu, particularly starch overload, favor rapid proliferation of this clostridial bacterium, large amounts of ETX can be elaborated. When sufficient toxin is absorbed from the intestine into the systemic circulation and reaches the brain, two neurologic syndromes can develop from this enterotoxemia. If the brain is exposed to large amounts of ETX, the lesions are fundamentally vasculocentric. The neurotoxin binds to microvascular endothelial receptors and other brain cells, the resulting damage causing increased vascular permeability and extravasation of plasma protein and abundant fluid into the brain parenchyma. While plasma protein, particularly albumin, pools largely perivascularly, the vasogenic edema becomes widely distributed in the brain, leading to a marked rise in intracranial pressure, coma, sometimes cerebellar herniation, and, eventually, often death. When smaller quantities of ETX are absorbed into the bloodstream, or livestock are partially immune, a more protracted clinical course ensues. The resulting brain injury is characterized by bilaterally symmetrical necrotic foci in certain selectively vulnerable neuroanatomic sites, termed focal symmetrical encephalomalacia. ETX has also been internationally listed as a potential bioterrorism agent. Although there are no confirmed human cases of ETX intoxication, the relatively wide species susceptibility to this toxin and its high toxicity mean it is likely that human populations would also be vulnerable to its neurotoxic actions. While the pathogenesis of ETX toxicity in the brain is incompletely understood, the putative mechanisms involved in neural lesion development are discussed

Pathogenesis and diagnostic features of brain and ophthalmic damage produced by Clostridium perfringens type D epsilon toxin

Clostridium perfringens type D epsilon toxin (EXT) causes an important neurologic disorder of sheep, goats and, rarely, cattle. The disease can occur in peracute, acute, subacute, and chronic forms. High circulating levels of ETX produce vasculocentric brain lesions, in which microvascular endothelial injury results in diagnostically useful perivascular and intramural extravasations of plasma protein, especially in sheep, and less frequently in goats. With lower toxin doses, a more protracted clinical course tends to occur, particularly in sheep, leading to focal, bilaterally symmetrical, necrotic foci in certain brain regions. Although these morphologic features usually permit the diagnostic pathologist to make a definitive etiologic diagnosis, there are many aspects of the pathogenesis of these cerebral lesions that are not completely understood. ETX has also been shown to produce microvascular damage in the retina of rats, resulting in severe, diffuse vasogenic edema, similar to that found in brains exposed to this neurotoxin. The pathoclisis and vascular theories offer alternative explanations of the differential susceptibility of different brain regions to the same neurotoxic insult

Clostridium perfringens type D epsilon toxin produces a rapid and dose-dependent cytotoxic effect on cerebral microvascular endothelial cells in vitro

Clostridium perfringens type D epsilon toxin (ETX) is responsible for a severe and frequently fatal neurologic disorder in ruminant livestock. Light microscopic, immunohistochemical, and ultrastructural studies have suggested that ETX injury to the cerebral microvasculature, with subsequent severe, generalized vasogenic edema and increased intracranial pressure, is critically important in producing neurologic dysfunction. However, the effect of ETX on brain capillary endothelial cells in vitro has not been examined previously, to our knowledge. We exposed a well-characterized human blood-brain barrier cell line to increasing concentrations of ETX, and demonstrated a direct and dose-dependent endotheliotoxic effect. Our findings are concordant with the primacy of vasculocentric brain lesions in the diagnosis of acute epsilon toxin enterotoxemia in ruminant livestock

The Australian Centre for RF Bioeffects Research: an NHMRC Centre of Research Excellence

Abstract not available

Use of Arterial Catheters in the Management of Acute Aortic Dissection

PURPOSE: The aim of this study was to investigate the relationship between the use of invasive arterial blood pressure (IBP) monitoring and reaching established aggressive medical management goals in acute aortic dissection. METHODS: Data were collected through a retrospective chart review of patients diagnosed with acute aortic syndromes of the thoracic cavity who required transport to tertiary care over a 28-month period. The 2010 American Heart Association medical management goals of thoracic aortic disease were used as hemodynamic end points. RESULTS: A total of 208 patients were included, with 113 (54%) diagnosed at least in part with acute Stanford Type A aortic dissections and the remaining 95 (46%) having isolated Stanford Type B dissections. Emergency departments made up 158 (76%) of transfer departments; 129 (62%) patients had IBP catheters placed. The highest mean systolic blood pressures (SBPs) recorded were 165 mm Hg in the IBP group versus 151 mm Hg when noninvasive blood pressure (NIBP) cuffs were used (P < .01). The mean decrease in SBP during transport was 51 mm Hg in the IBP group versus 34 mm Hg in the NIBP group (P < .001). The difference between the last reported NIBP and the first IBP was noted as 19 mm Hg higher. The IBP group met the SBP goal more frequently than the NIBP group (P < .05) when the SBP was noted as greater than 140 mm Hg during transport. Bedside time increased only 6 minutes with IBP placement (P < .007). CONCLUSION: Patients with IBP catheters were noted to be more aggressively managed with antihypertensive medications, met hemodynamic goals more frequently, and had only 6 minutes longer bedside times. These findings support the placement of IBP catheters by emergency departments and critical care transport (CCT) teams in patients with acute aortic syndromes requiring interfacility transport to definitive care