Current Issue : July - September Volume : 2012 Issue Number : 3 Articles : 5 Articles
Background: Bacterial cell lysis is a widely studied mechanism that can be achieved through the intracellular\r\nexpression of phage native lytic proteins. This mechanism can be exploited for programmed cell death and for\r\ngentle cell disruption to release recombinant proteins when in vivo secretion is not feasible. Several genetic parts\r\nfor cell lysis have been developed and their quantitative characterization is an essential step to enable the\r\nengineering of synthetic lytic systems with predictable behavior.\r\nResults: Here, a BioBrickââ??¢ lysis device present in the Registry of Standard Biological Parts has been quantitatively\r\ncharacterized. Its activity has been measured in E. coli by assembling the device under the control of a well\r\ncharacterized N-3-oxohexanoyl-L-homoserine lactone (HSL) -inducible promoter and the transfer function, lysis\r\ndynamics, protein release capability and genotypic and phenotypic stability of the device have been evaluated.\r\nFinally, its modularity was tested by assembling the device to a different inducible promoter, which can be\r\ntriggered by heat induction.\r\nConclusions: The studied device is suitable for recombinant protein release as 96% of the total amount of the\r\nintracellular proteins was successfully released into the medium. Furthermore, it has been shown that the device\r\ncan be assembled to different input devices to trigger cell lysis in response to a user-defined signal. For this\r\nreason, this lysis device can be a useful tool for the rational design and construction of complex synthetic\r\nbiological systems composed by biological parts with known and well characterized function. Conversely, the onset\r\nof mutants makes this device unsuitable for the programmed cell death of a bacterial population....
Hybrid combinatorial chemistry strategies that use DNA as an information-carrying medium are proving to be powerful\r\ntools for molecular discovery. In order to extend these efforts, we present a highly parallel format for DNA-programmed\r\nchemical library synthesis. The new format uses a standard microwell plate footprint and is compatible with commercially\r\navailable automation technology. It can accommodate a wide variety of combinatorial synthetic schemes with up to 384\r\ndifferent building blocks per chemical step. We demonstrate that fluidic routing of DNA populations in the highly parallel\r\nformat occurs with excellent specificity, and that chemistry on DNA arrayed into 384 well plates proceeds robustly, two\r\nrequirements for the high-fidelity translation and efficient in vitro evolution of small molecules....
Asymmetric bi-soft segment poly(ester urethane urea) (PEUU) membranes containing polycaprolactone (PCL) as a second soft\r\nsegment are synthesized with PCL-diol ranging from 0% to 15% (w/w). Bulk and surface characteristics of the PEUU membranes\r\nwere investigated by scanning electron microscopy (SEM), static water contact angles, and surface streaming potentials and were\r\ncorrelated to hemocompatibility properties, namely, hemolysis and thrombosis degrees. SEM analysis reveals PEUU membranes\r\nwith asymmetric cross-sections and top dense surfaces with distinct morphologies. The increase in PCL-diol content yields PEUU\r\nmembranes with blood-contacting surfaces that are smoother, more hydrophilic, and with higher maximum zeta potentials. The\r\nresults obtained in this work give no evidence of a correlation between hydrophilicity/zeta potentials and the hemolysis/thrombosis\r\ndegree of blood-contacting surfaces of the PEUU membranes. In contrast, other hemocompatibility aspects reveal that the more\r\nhydrophilic membranes are associated with lower platelet deposition and inhibition of extreme states of platelet activation....
Background: During percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from\r\ncoronary lesions can result in distal embolization, and may lead to increased major adverse cardiovascular events\r\n(MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to\r\nremove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction\r\n(STEMI) undergoing PCI of native vessels.\r\nMethods: We conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science\r\n(January 1996-March 2011), http://www.clinicaltrials.gov, abstracts from major cardiology meetings, TCTMD, and\r\nCardioSource Plus. Two investigators independently screened citations and extracted data from randomized\r\ncontrolled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with\r\nSTEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one prespecified\r\noutcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high,\r\nmoderate, low or insufficient. Disagreement was resolved through consensus.\r\nResults: 37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI\r\nsignificantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also\r\nsignificantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by\r\n39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization\r\nby 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use\r\nof catheter aspiration devices increased procedural time upon qualitative assessment.\r\nDistal filter embolic protection devices significantly increased the risk of target revascularization by 39% although\r\nthe use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health\r\noutcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20%\r\nand TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon\r\nqualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly\r\nprolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is\r\nunclear due to insufficient amounts of data.\r\nConclusions: In patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long\r\nperiod of follow-up. Due to insufficient data, the safety of these devices is unclear....
Background: Academic literature and international standards bodies suggest that user involvement, via the\r\nincorporation of human factors engineering methods within the medical device design and development (MDDD)\r\nprocess, offer many benefits that enable the development of safer and more usable medical devices that are better\r\nsuited to usersââ?¬â?¢ needs. However, little research has been carried out to explore medical device manufacturersââ?¬â?¢\r\nbeliefs and attitudes towards user involvement within this process, or indeed what value they believe can be\r\nadded by doing so.\r\nMethods: In-depth interviews with representatives from 11 medical device manufacturers are carried out. We ask\r\nthem to specify who they believe the intended users of the device to be, who they consult to inform the MDDD\r\nprocess, what role they believe the user plays within this process, and what value (if any) they believe users add.\r\nThematic analysis is used to analyse the fully transcribed interview data, to gain insight into medical device\r\nmanufacturersââ?¬â?¢ beliefs and attitudes towards user involvement within the MDDD process.\r\nResults: A number of high-level themes emerged, relating who the user is perceived to be, the methods used, the\r\nperceived value and barriers to user involvement, and the nature of user contributions. The findings reveal that\r\ndespite standards agencies and academic literature offering strong support for the employment formal methods,\r\nmanufacturers are still hesitant due to a range of factors including: perceived barriers to obtaining ethical approval;\r\nthe speed at which such activity may be carried out; the belief that there is no need given the ââ?¬Ë?all-knowingââ?¬â?¢ nature\r\nof senior health care staff and clinical champions; a belief that effective results are achievable by consulting a\r\nminimal number of champions. Furthermore, less senior health care practitioners and patients were rarely seen as\r\nbeing able to provide valuable input into the process.\r\nConclusions: Medical device manufacturers often do not see the benefit of employing formal human factors\r\nengineering methods within the MDDD process. Research is required to better understand the day-to-day\r\nrequirements of manufacturers within this sector. The development of new or adapted methods may be required\r\nif user involvement is to be fully realised....
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