ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary

These guidelines address the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic peripheral arterial diseases (PADs). The clinical manifestations of PAD are a major cause of acute and chronic illness, are associated with decrements in functional capacity and quality of life, cause limb amputation, and increase the risk of death. Whereas the term “peripheral arterial disease” encompasses a large series of disorders that affect arterial beds exclusive of the coronary arteries, this writing committee chose to limit the scope of the work of this document to include the disorders of the abdominal aorta, renal and mesenteric arteries, and lower extremity arteries. The purposes of the full guidelines are to (a) aid in the recognition, diagnosis, and treatment of PAD of the aorta and lower extremities, addressing its prevalence, impact on quality of life, cardiovascular ischemic risk, and risk of critical limb ischemia (CLI); (b) aid in the recognition, diagnosis, and treatment of renal and visceral arterial diseases; and (c) improve the detection and treatment of abdominal and branch artery aneurysms. Clinical management guidelines for other arterial beds (e.g., the thoracic aorta, carotid and vertebral arteries, and upper-extremity arteries) have been excluded from the current guidelines to focus on the infradiaphragmatic arterial system and in recognition of the robust evidence base that exists for the aortic, visceral, and lower extremity arteries

pH-responsive virus-based colloidal crystals for advanced material platforms

Bacteriophages have a well-defined nanoscale size, shape, and surface chemistry, making them promising candidates for creating advanced biomaterials for applications including biocatalysis, drug delivery, and biosensing. This study demonstrates the self-assembly of the ≈29 nm diameter bacteriophage Qbeta (Qubevirus durum) with the synthetic polycation, poly [2-(methacryloyloxy)ethyl] trimethylammonium chloride (pMETAC), into compartmentalized colloidal crystals. The pH and the polymer chain length tune their self-assembly and the resulting structure, with the potential for further chemical modification or loading with bioactive molecules. Small angle X-ray scattering (SAXS), multi-angle dynamic light scattering (DLS), and atomic force microscopy (AFM) are used for studying the Qbeta self-assembly into the geometrically ordered aggregates. The suprastructures form at pH > 7.0 and disassemble at pH < 7.0. Zeta potential measurements and X-ray photoelectron spectroscopy (XPS) show pMETAC adsorption onto the negatively charged Qbeta surface. The colloidal crystal formation is achieved without chemically modifying the Qbeta surface. Additionally, the Qbeta/pMETAC suprastructures can be easily separated from the suspension as macroscopic aggregate, maintaining their activity. Their simple preparation allows for large-scale production of advanced materials in food and health science applications and nanotechnology. The insights from this study will further advance the tailored design and production of novel colloidal materials

Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis

Matrix metalloproteinase 9 (MMP-9) has a key role in many biological processes, and while it is crucial for a normal immune response, excessive release of this enzyme can lead to severe tissue damage, as evidenced by proteolytic digestion and perforation of the cornea during infectious keratitis. Current medical management strategies for keratitis mostly focus on antibacterial effects, but largely neglect the role of excess MMP activity. Here, a cyclic tissue inhibitor of metalloproteinase (TIMP) peptidomimetic, which downregulated MMP-9 expression both at the mRNA and protein levels as well as MMP-9 activity in THP-1-derived macrophages, is reported. A similar downregulating effect could also be observed on α smooth muscle actin (α-SMA) expression in fibroblasts. Furthermore, the TIMP peptidomimetic reduced Pseudomonas aeruginosa-induced MMP-9 activity in an ex vivo porcine infectious keratitis model and histological examinations demonstrated that a decrease of corneal thickness, associated with keratitis progression, was inhibited upon peptidomimetic treatment. The presented approach to reduce MMP-9 activity thus holds great potential to decrease corneal tissue damage and improve the clinical success of current treatment strategies for infectious keratitis

Scalable Synthesis of Self‐Disinfecting Polycationic Coatings for Hospital Relevant Surfaces

Abstract The prevention of microbial infections is a global challenge. Efficient antimicrobial coatings that rapidly kill microorganisms upon contact can help minimize their transmission. However, their scalable synthesis is challenging. This work demonstrates the scalable synthesis and characterization of self‐disinfecting nanofilms for the postmodification of hospital‐relevant surfaces. Their antimicrobial action is based on charge interactions between a supercharged cationic surface film and the negatively charged bacteria membrane. Photoinitiated bulk polymerization of an air‐dried [2‐(methacryloyloxy)ethyl]trimethylammonium chloride film on cotton (gowns), nitrile rubber (protective gloves), and glass surfaces (tables, screens) is used for their supercharging, and studied with streaming potential measurements. A 6 nm thick coating dominated by cationic quarternary amine groups is shown by a combination of spectroscopic imaging ellipsometry and X‐ray photoelectron spectroscopy. Antimicrobial in vitro evaluation of the coated surfaces demonstrates up to ≈4 log reductions in bacterial populations in less than 5 min. Confocal laser scanning microscopy and live‐dead staining confirm the surface‐induced killing of bacteria. The coating's range of compatible materials and its rapid bactericidal activity can combat the surface transmission of bacteria and may help to contain the spread of infectious diseases. Its synthesis in environmental conditions is promising for integration into industrial processes

Substrate viscosity plays an important role in bacterial adhesion under fluid flow

Many materials used in the medical settings such as catheters and contact lenses as well as most biological tissues are not purely elastic, but rather viscoelastic. While substrate elasticity has been investigated for its influence on bacterial adhesion, the impact of substrate viscosity has not been explored. Here, the importance of considering substrate viscosity is explored by using polydimethylsiloxane (PDMS) as the substrate material, whose mechanical properties can be tuned from predominantly elastic to viscous by varying cross-linking degree. Interfacial rheology and atomic force microscopy analysis prove that PDMS with a low cross-linking degree exhibits both low stiffness and high viscosity. This degree of viscoelasticity confers to PDMS a remarkable stress relaxation, a good capability to deform and an increased adhesive force. Bacterial adhesion assays were conducted under flow conditions to study the impact of substrate viscosity on Escherichia coli adhesion. The viscous PDMS not only enhanced E. coli adhesion but also conferred greater resistance to desorption against shear stress at air/liquid interface, compared to the PDMS with high crosslinking degree. These findings highlight the importance to consider substrate viscosity while studying bacterial adhesion. The current work provides new insights to an improved understanding of how bacteria interact with complex viscoelastic environments. (C) 2019 The Authors. Published by Elsevier Inc

Substrate viscosity plays an important role in bacterial adhesion under fluid flow

Many materials used in the medical settings such as catheters and contact lenses as well as most biological tissues are not purely elastic, but rather viscoelastic. While substrate elasticity has been investigated for its influence on bacterial adhesion, the impact of substrate viscosity has not been explored. Here, the importance of considering substrate viscosity is explored by using polydimethylsiloxane (PDMS) as the substrate material, whose mechanical properties can be tuned from predominantly elastic to viscous by varying cross-linking degree. Interfacial rheology and atomic force microscopy analysis prove that PDMS with a low cross-linking degree exhibits both low stiffness and high viscosity. This degree of viscoelasticity confers to PDMS a remarkable stress relaxation, a good capability to deform and an increased adhesive force. Bacterial adhesion assays were conducted under flow conditions to study the impact of substrate viscosity on Escherichia coli adhesion. The viscous PDMS not only enhanced E. coli adhesion but also conferred greater resistance to desorption against shear stress at air/liquid interface, compared to the PDMS with high crosslinking degree. These findings highlight the importance to consider substrate viscosity while studying bacterial adhesion. The current work provides new insights to an improved understanding of how bacteria interact with complex viscoelastic environments.ISSN:0021-9797ISSN:1095-710

Guanylated Polymethacrylates: A Class of Potent Antimicrobial Polymers with Low Hemolytic Activity

We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure–activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition–fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity