Blood Conservation and Hemostasis in Cardiac Surgery: A Survey of Practice Variation and Adoption of Evidence-Based Guidelines.

BACKGROUND: Blood conservation and hemostasis are integral parts of reducing avoidable blood transfusions and the associated morbidity and mortality. Despite the publication of blood conservation guidelines for cardiac surgery, evidence suggests persistent variability in practice patterns. Members of the Society of Cardiovascular Anesthesiologists (SCA) created a survey to audit conformance to existing guidelines and use the results to help narrow the evidence-to-practice gap. METHODS: Members of the SCA and its Continuous Practice Improvement (CPI)- Blood Conservation Work Group developed a 48-item Blood Conservation and Hemostasis in Cardiac Surgery (BCHCS) survey. The questionnaire included the components of the Anesthesia Quality Institute's (AQI) composite measure AQI49. The survey was distributed to the entire SCA membership by e-mail via the Research Electronic Data Capture (REDCap) Consortium between the fall of 2017 and early 2018. RESULTS: Of 3152 SCA members, 536 returned surveys for a response rate of 17%. Most responders worked at academic institutions. The median transfusion trigger after cardiopulmonary bypass was hemoglobin (Hgb) 7.0 to 8.0 g/dL. There are 4 components to AQI49, and the composite conformance to all of them was low due to 1 specific component: the use of transfusion algorithms supplemented with point-of-care (POC) testing. There was good conformance to the other 3 components of AQI49: use of antifibrinolytics, minimization of hemodilution and use of red cell salvage. Overall, practices with a multidisciplinary patient blood management (PBM) team were the most successful in meeting all 4 AQI49 criteria. CONCLUSIONS: The survey demonstrated widespread adoption of several best practices, including the tolerance of lower hemoglobin transfusion triggers, use of antifibrinolytics, minimization of hemodilution, and use of red cell salvage. The survey also confirms that gaps remain in preoperative anemia management and the use of transfusion algorithms supplemented with POC hemostasis testing. Serial use of this survey can be used to identify barriers to implementation and audit the effectiveness of interventions described in this article. This instrument could also help harmonize local, regional, and national efforts and become an essential component of an implementation strategy for PBM in cardiac surgery.

Growth and structural discrimination of cortical neurons on randomly oriented and vertically aligned dense carbon nanotube networks.

The growth of cortical neurons on three dimensional structures of spatially defined (structured) randomly oriented, as well as on vertically aligned, carbon nanotubes (CNT) is studied. Cortical neurons are attracted towards both types of CNT nano-architectures. For both, neurons form clusters in close vicinity to the CNT structures whereupon the randomly oriented CNTs are more closely colonised than the CNT pillars. Neurons develop communication paths via neurites on both nanoarchitectures. These neuron cells attach preferentially on the CNT sidewalls of the vertically aligned CNT architecture instead than onto the tips of the individual CNT pillars.

Hydrogen bonding in neutral and cation dimers of H2Se with H2O, H2S, and H2Se.

Structures, hydrogen bonding, and binding energies of H(4)SeA (A = O, S, Se) dimers and their cation radicals have been studied using DFT-B3LYP, MP2, and CCSD methods with 6-31++G(d,p), cc-pVTZ, and aug-cc-pVTZ basis sets. The binding energy (BE) order of the most stable neutral and cationic dimers have been found to be (H(2)Se···HOH) > (H(2)Se···HSH) > (H(2)Se···HSeH), and (H(2)Se···SeH(2))(+) > (H(2)Se···SH(2))(+) > (HSe···HOH(2))(+), respectively, by B3LYP/6-31++G(d,p) and MP2/aug-cc-pVTZ methods. Higher electronegativity of the heteroatom has been found to result in more stability of the neutral dimer but less of the cationic dimer. Among neutral dimers, structure with more electronegative heteroatom acting as proton donor has been found to be more stable. However, the hemibonded structure has been found to be more stable for the dimer cation radical unless the ionization potentials of the involved heteroatoms are very different, e.g., H(4)SeO(+). Vibrational frequency calculation suggests that an increase in electronegativity of A-atom results in a decrease in Se-H bond strength in H(4)SeA and H(4)SeA(+) dimers. The calculated values of Mulliken atomic charge/spin and hydrogen bond lengths of the dimers and their radical cations have also been discussed.

Three-dimensional carbon nanotube electrodes for extracellular recording of cardiac myocytes.

Low impedance at the interface between tissue and conducting electrodes is of utmost importance for the electrical recording or stimulation of heart and brain tissue. A common way to improve the cell-metal interface and thus the signal-to-noise ratio of recordings, as well as the charge transfer for stimulation applications, is to increase the electrochemically active electrode surface area. In this paper, we propose a method to decrease the impedance of microelectrodes by the introduction of carbon nanotubes (CNTs), offering an extremely rough surface. In a multistage process, an array of multiple microelectrodes covered with high quality, tightly bound CNTs was realized. It is shown by impedance spectroscopy and cardiac myocyte recordings that the transducer properties of the carbon nanotube electrodes are superior to conventional gold and titanium nitride electrodes. These findings will be favorable for any kind of implantable heart electrodes and electrophysiology in cardiac myocyte cultures.

Hierarchical structures of carbon nanotubes and arrays of chromium-capped silicon nanopillars: formation and electrical properties.

The formation of stochastically oriented carbon-nanotube networks on top of an array of free-standing chromium-capped silicon nanopillars is reported. The combination of nanosphere lithography and chemical vapor deposition enables the construction of nanostructures that exhibit a hierarchical sequence of structural sizes. Metallic chromium serves as an etching mask for Si-pillar formation and as a nucleation site for the formation of carbon nanotubes through the chemical vapor deposition of ethene, ethanol, and methane, respectively, thereby bridging individual pillars from top to top. Iron and cobalt were applied onto the chromium caps as catalysts for CNT growth and the influence of different carbon sources and different gas-flow rates were investigated. The carbon nanotubes were structurally characterized and their DC electrical properties were studied by in situ local- and ex situ macroscopic measurements, both of which reveal their semiconductor properties. This process demonstrates how carbon nanotubes can be integrated into Si-based semiconductors and, thus, this process may be used to form high-surface-area sensors or new porous catalyst supports with enhanced gas-permeation properties.

Assembly of one dimensional inorganic nanostructures into functional 2D and 3D architectures. Synthesis, arrangement and functionality.

This review will focus on the synthesis, arrangement, structural assembly, for current and future applications, of 1D nanomaterials (tubes, wires, rods) in 2D and 3D ordered arrangements. The ability to synthesize and arrange one dimensional nanomaterials into ordered 2D or 3D micro or macro sized structures is of utmost importance in developing new devices and applications of these materials. Micro and macro sized architectures based on such 1D nanomaterials (e.g. tubes, wires, rods) provide a platform to integrate nanostructures at a larger and thus manageable scale into high performance electronic devices like field effect transistors, as chemo- and biosensors, catalysts, or in energy material applications. Carbon based, metal oxide and metal based 1D arranged materials as well as hybrid or composite 1D materials of the latter provide a broad materials platform, offering a perspective for new entries into fascinating structures and future applications of such assembled architectures. These architectures allow bridging the gap between 1D nanostructures and the micro and macro world and are the basis for an assembly of 1D materials into higher hierarchy domains. This critical review is intended to provide an interesting starting point to view the current state of the art and show perspectives for future developments in this field. The emphasis is on selected nanomaterials and the possibilities for building three dimensional arrays starting from one dimensional building blocks. Carbon nanotubes, metal oxide nanotubes and nanowires (e.g. ZnO, TiO(2), V(2)O(5), Cu(2)O, NiO, Fe(2)O(3)), silicon and germanium nanowires, and group III-V or II-VI based 1D semiconductor nanostructures like GaS and GaN, pure metals as well as 1D hybrid materials and their higher organized architectures (foremost in 3D) will be focussed. These materials have been the most intensively studied within the last 5-10 years with respect to nano-micro integration aspects and their functional and application oriented properties. The critical review should be interesting for a broader scientific community (chemists, physicists, material scientists) interested in synthetic and functional material aspects of 1D materials as well as their integration into next higher organized architectures.

Degradation of dichlorvos using hydrodynamic cavitation based treatment strategies.

The degradation of an aqueous solution of dichlorvos, a commonly used pesticide in India, has been systematically investigated using hydrodynamic cavitation reactor. All the experiments have been carried out using a 20 ppm solution of commercially available dichlorvos. The effect of important operating parameters such as inlet pressure (over a range 3-6 bar), temperature (31 °C, 36 °C and 39 °C) and pH (natural pH = 5.7 and acidic pH = 3) on the extent of degradation has been investigated initially. It has been observed that an optimum value of pressure gives maximum degradation whereas low temperature and pH of 3 are favorable. Intensification studies have been carried out using different additives such as hydrogen peroxide, carbon tetrachloride, and Fenton's reagent. Use of hydrogen peroxide and carbon tetrachloride resulted in the enhancement of the extent of degradation at optimized conditions but significant enhancement was obtained with the combined use of hydrodynamic cavitation and Fenton's chemistry. The maximum extent of degradation as obtained by using a combination of hydrodynamic cavitation and Fenton's chemistry was 91.5% in 1h of treatment time. The present work has conclusively established that hydrodynamic cavitation in combination with Fenton's chemistry can be effectively used for the degradation of dichlorvos.

Antioxidant activity and free radical scavenging reactions of gentisic acid: in-vitro and pulse radiolysis studies.

Abstract Antioxidant activity of gentisic acid has been studied using fast chemical kinetics and two in vitro models, namely the isolated rat liver mitochondria (RLM) and the human erythrocytes. The presence of gentisic acid (GA) during irradiation significantly reduced the levels of gamma radiation induced damages to lipids and proteins in RLM. Further, GA imparted protection to the human erythrocytes against exposure to gamma radiation. Molecular mechanism of free radical scavenging reactions has been evaluated with the help of rate constants and transients obtained from gentisic acid using pulse radiolysis technique. GA efficiently scavenged hydroxyl radical (k = 1.1 × 10(10) dm(3)mol(-1)s(-1)) to produce reducing adduct radical (~76%) and oxidizing phenoxyl radical (~24%). GA has also scavenged organohaloperoxyl radical (k = 9.3 × 10(7) dm(3) mol(-1)s(-1)). Ascorbate has been found to repair phenoxyl radical of GA (k = 1.0 × 10(7) dm(3)mol(-1)s(-1)). Redox potential value of GA(•)/GA couple (0.774 V vs NHE) obtained by cyclic voltammetry is less than those of physiologically important oxidants, which supports the observed antioxidant capacity of GA. We, therefore, propose that the antioxidant and radioprotective properties of GA are exerted by its phenoxyl group.

Gas phase synthesis and field emission properties of 3D aligned double walled carbon nanotube/anatase hybrid architectures.

A 3D hybrid architecture composed of macroscopic, vertically aligned CNT blocks which are formed via a metal catalyzed CVD process followed by deposition of TiO(2) on the CNT side walls in nanocrystalline or amorphous form is presented. The morphology of the deposited TiO(2) can be tailored by the deposition method employed. Depositing TiO(2) from the gas phase by employing the organometallic precursor Ti[OCH(CH(3))(2)](4) leads to formation of nanocrystalline anatase or rutile particles with a dense coverage on the surface and within the 3D CNT scaffold. Phase pure TiO(2) (anatase) is formed between 500 and 700 °C, while higher temperatures resulted in rutile modification of TiO(2). Below 500 °C, TiO(2) forms an amorphous oxide layer. At higher temperatures such initially formed TiO(2) layers segregate into particles which tend to crystallize. In contrast, when generating TiO(2) by oxidation of Ti metal which is deposited by vaporization onto the 3D CNT block array, and subsequently oxidized in air or controlled O(2) atmosphere this leads to a porous layer with a particular nanostructure on top of the CNT blocks. First studies of the fabrication and field emission of the new 3D CNT/TiO(2) hybrid cathodes display good and stable FE characteristics with onset fields for current density of 1 µA cm(-2) of 1.7 to 1.9 V µm(-1), while the average field enhancement factor is in the range between 2000 and 2500 depending on the O(2) base pressure during the measurements.

Generation and agglomeration behaviour of size-selected sub-nm iron clusters as catalysts for the growth of carbon nanotubes.

Mass-selected, ligand-free Fe(N) clusters with N = 10-30 atoms (cluster diameter: 0.6-0.9 nm) were implanted into [Al@SiO(x)] surfaces at a low surface coverage corresponding to a few thousandths up to a few hundredths of a monolayer in order to avoid initial cluster agglomeration. These studies are aimed towards gaining an insight into the lower limit of the size regime of carbon nanotube (CNT) growth by employing size-selected sub-nm iron clusters as catalyst or precatalyst precursors for CNT growth. Agglomeration of sub-nm iron clusters to iron nanoparticles with a median size range between three and six nanometres and the CNT formation hence can be observed at CVD growth temperatures of 750 °C. Below 600 °C, no CNT growth is observed.

Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation.

Engineering of protein-protein interactions is used to enhance the affinity or specificity of proteins, such as antibodies or protease inhibitors, for their targets. However, fully diversifying all residues in a protein-protein interface is often unfeasible. Therefore, we limited our phage library for the serine protease inhibitor ecotin by restricting it to only tetranomial diversity and then targeted all 20 amino acid residues involved in protein recognition. This resulted in a high-affinity and highly specific plasma kallikrein inhibitor, ecotin-Pkal. To validate this approach we dissected the energetic contributions of each wild type (wt) or mutated surface loop to the binding of either plasma kallikrein (PKal) or membrane-type serine protease 1. The analysis demonstrated that a mutation in one loop has opposing effects depending on the sequence of surrounding loops. This finding stresses the cooperative nature of loop-loop interactions and justifies targeting multiple loops with a limited diversity. In contrast to ecotin wt, the specific loop combination of ecotin-Pkal discriminates the subtle structural differences between the active enzymes, PKal and Factor XIIa, and their respective zymogen forms. We used ecotin-Pkal to specifically inhibit contact activation of human plasma at the level mediated by plasma kallikrein.

Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution.

The plasminogen cascade of serine proteases directs both development and tumorigenesis in the mammary gland. Plasminogen can be activated to plasmin by urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasma kallikrein (PKal). The dominant plasminogen activator for mammary involution is PKal, a serine protease that participates in the contact activation system of blood coagulation. We observed that the prekallikrein gene (Klkb1) is expressed highly in the mammary gland during stromal remodeling periods including puberty and postlactational involution. We used a variant of ecotin (ecotin-PKal), a macromolecular inhibitor of serine proteases engineered to be highly specific for active PKal, to demonstrate that inhibition of PKal with ecotin-PKal delays alveolar apoptosis, adipocyte replenishment, and stromal remodeling in the involuting mammary gland, producing a phenotype resembling that resulting from plasminogen deficiency. Using biotinylated ecotin-PKal, we localized active PKal to connective tissue-type mast cells in the mammary gland. Taken together, these results implicate PKal as an effector of the plasminogen cascade during mammary development.

Serum micronutrient and micromineral concentrations and ratios in healthy Omani subjects.

OBJECTIVE: This study aimed to establish reference ranges of serum concentrations of copper, zinc, retinol, alpha-tocopherol, copper:caeruloplasmin and copper:zinc ratios in a group of healthy Omani men and women. MATERIALS AND METHODS: Assay techniques employed were atomic absorption spectrophotometry (copper and zinc), reverse-phase high-pressure liquid chromatography with isocratic elution (retinol and alpha-tocopherol), immunonephelometry (caeruloplasmin) and spectrophotometry (albumin and cholesterol). RESULTS: The mean +/- SD (microM) obtained for copper, zinc, retinol, and alpha-tocopherol were 15.9 +/- 3.0, 14.2 +/- 2.0, 1.45 +/- 0.39 and 16.9 +/- 4.4, respectively. The mean +/- SD for copper:zinc and copper:caeruloplasmin ratios were 1.15 +/- 0.30 micromol/mmol and 6.99 +/- 0.84 micromol/g, respectively. Significantly higher (p < 0.0001) copper and caeruloplasmin concentrations, copper:zinc and copper:caeruloplasmin ratios and lower zinc, retinol, alpha-tocopherol, cholesterol concentrations and alpha-tocopherol:cholesterol ratio were present in women compared to men. Age appeared to be associated with copper and retinol concentrations, and copper:caeruloplasmin ratios in women; in men, the association was mostly moderate with caeruloplasmin, alpha-tocopherol, cholesterol concentrations and alpha-tocopherol:cholesterol ratios. Smokers had decreased albumin (p = 0.002), zinc (p = 0.023) concentrations, and copper:caeruloplasmin ratios (p = 0.002), increased alpha-tocopherol concentrations (p = 0.016) and alpha-tocopherol:cholesterol ratios (p = 0.021) compared with non-smokers. Deficiency incidence was < or =5% for all investigated parameters. CONCLUSIONS: Reference ranges of micronutrient concentrations and micromineral ratios were established for Omani subjects. The mean values of several micronutrients were lower than those reported for other populations and some showed gender effects.

In vivo radioprotection by 5-aminosalicylic acid.

The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7x10(9)M(-1)s(-1). The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21.

Ionized state of hydroperoxy radical-water hydrogen-bonded complex: (HO2-H2O)+.

Ab initio molecular orbital calculations have been employed to characterize the structure and bonding of the (HO2-H2O)+ radical cation system. Geometry optimization of this system was carried out using unrestricted density functional theory in conjunction with the BHHLYP functional and 6-311++G(2df,2p) as well as 6-311++G(3df,3p) basis sets, the second-order Møller-Plesset perturbation (MP2) method with the 6-311++G(3df,3p) basis set, and the couple cluster (CCSD) method with the aug-cc-pVTZ basis set. The effect of spin multiplicity on the stability of the (HO2-H2O)+ system has been studied and also compared with that of oxygen. The calculated results suggest a proton-transferred hydrogen bond between HO2 and H2O in H3O3+ wherein a proton is partially transferred to H2O producing the O2...H3O+ structure. The basis set superposition error and zero-point energy corrected results indicate that the H3O3+ system is energetically more stable in the triplet state; however, the singlet state of H3O3+ is more stable with respect to its dissociation into H3O+ and singlet O2. Since the resulting proton-transferred hydrogen-bonded complex (O2...H3O+) consists of weakly bound molecular oxygen, it might have important implications in various chemical processes and aquatic life systems.