2,358 research outputs found

    Thermoreversible gels for the encapsulation of macrophages: evaluation of polymer type on rheology and cytocompatibility

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    Thermoresponsive polymers have become a highly sought-after “smart material” due to their ability to modify their physical characteristics due to temperature changes. This research aimed to determine the biocompatibility of specific thermoreversible gels for immunocompetent cell models containing ImmuPHAGETM, human alveolar macrophage-like cells. Four polymers were selected based on their transition temperatures, including three commercially available pharmaceutical excipients, namely poloxamer 407, soluplus, and methylcellulose. The fourth system, poly(N-isopropyl acrylamide)-b-poly(ethylene oxide)-b-poly(N-isopropyl acrylamide), was synthesised in-house. Initially, the phase behaviour of these four polymers was evaluated visually by warming the polymer solutions and determining the state of the solution by vial inversion. Subsequently, a combination of rheological measurements was employed to compare the properties of these thermoreversible gels in culture media. The physical characterisation was followed by conducting cytocompatibility tests using human alveolar macrophages to assess their suitability as a scaffold for cell culture in vitro and to determine the cell response to different culturing environments. The study concluded that methylcellulose is the most promising and cost-effective material worth further exploration as a responsive matrix for immune cell encapsulation. Keywords: Thermoresponsive, Thermogelling, Alveolar macrophages, Foamy macrophages, immunocompetent in vitro models

    Combining branched copolymers with additives generates stable thermoresponsive emulsions with in situ gelation upon exposure to body temperature

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    Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol–gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form

    Supramolecular materials: longer and safer gastric residence

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    A supramolecular polymer that is stable in the acidic environment of the stomach but dissolves in the neutral-pH environment of the intestines prolongs the safe retention of gastric devices

    The Influence of Physiological Status on age Prediction of Anopheles Arabiensis Using Near Infra-red spectroscopy

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    Determining the age of malaria vectors is essential for evaluating the impact of interventions that reduce the survival of wild mosquito populations and for estimating changes in vectorial capacity. Near infra-red spectroscopy (NIRS) is a simple and non-destructive method that has been used to determine the age and species of Anopheles gambiae s.l. by analyzing differences in absorption spectra. The spectra are affected by biochemical changes that occur during the life of a mosquito and could be influenced by senescence and also the life history of the mosquito, i.e., mating, blood feeding and egg-laying events. To better understand these changes, we evaluated the influence of mosquito physiological status on NIR energy absorption spectra. Mosquitoes were kept in individual cups to permit record keeping of each individual insect’s life history. Mosquitoes of the same chronological age, but at different physiological stages, were scanned and compared using cross-validations. We observed a slight trend within some physiological stages that suggest older insects tend to be predicted as being physiologically more mature. It was advantageous to include mosquitoes of different chronological ages and physiological stages in calibrations, as it increases the robustness of the model resulting in better age predictions. Progression through different physiological statuses of An. arabiensis influences the chronological age prediction by the NIRS. Entomologists that wish to use NIR technology to predict the age of field-caught An. gambiae s.l from their study area should use a calibration developed from their field strain using mosquitoes of diverse chronological ages and physiological stages to increase the robustness and accuracy of the predictions.\u

    Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine initiative: patient-centred outcomes

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    BACKGROUND: Patient-centred outcomes are increasingly used in perioperative clinical trials. The Standardised Endpoints in Perioperative Medicine (StEP) initiative aims to define which measures should be used in future research to facilitate comparison between studies and to enable robust evidence synthesis. METHODS: A systematic review was conducted to create a longlist of patient satisfaction, health-related quality of life, functional status, patient well-being, and life-impact measures for consideration. A three-stage Delphi consensus process involving 89 international experts was then conducted in order to refine this list into a set of recommendations. RESULTS: The literature review yielded six patient-satisfaction measures, seven generic health-related quality-of-life measures, eight patient well-being measures, five functional-status measures, and five life-impact measures for consideration. The Delphi response rates were 92%, 87%, and 100% for Rounds 1, 2, and 3, respectively. Three additional measures were added during the Delphi process as a result of contributions from the StEP group members. Firm recommendations have been made about one health-related quality-of-life measure (EuroQol 5 Dimension, five-level version with visual analogue scale), one functional-status measure (WHO Disability Assessment Schedule version 2.0, 12-question version), and one life-impact measure (days alive and out of hospital at 30 days after surgery). Recommendations with caveats have been made about the Bauer patient-satisfaction measure and two life-impact measures (days alive and out of hospital at 1 yr after surgery, and discharge destination). CONCLUSIONS: Several patient-centred outcome measures have been recommended for use in future perioperative studies. We suggest that every clinical study should consider using at least one patient-centred outcome within a suite of endpoints

    Cohort profile: Examining Neighbourhood Activities in Built Living Environments in London: the ENABLE London-Olympic Park cohort.

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    PURPOSE: The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) project is a natural experiment which aims to establish whether physical activity and other health behaviours show sustained changes among individuals and families relocating to East Village (formerly the London 2012 Olympics Athletes' Village), when compared with a control population living outside East Village throughout. PARTICIPANTS: Between January 2013 and December 2015, 1497 individuals from 1006 households were recruited and assessed (at baseline) (including 392 households seeking social housing, 421 seeking intermediate and 193 seeking market rent homes). The 2-year follow-up rate is 62% of households to date, of which 57% have moved to East Village. FINDINGS TO DATE: Assessments of physical activity (measured objectively using accelerometers) combined with Global Positioning System technology and Geographic Information System mapping of the local area are being used to characterise physical activity patterns and location among study participants and assess the attributes of the environments to which they are exposed. Assessments of body composition, based on weight, height and bioelectrical impedance, have been made and detailed participant questionnaires provide information on socioeconomic position, general health/health status, well-being, anxiety, depression, attitudes to leisure time activities and other personal, social and environmental influences on physical activity, including the use of recreational space and facilities in their residential neighbourhood. FUTURE PLANS: The main analyses will examine the changes in physical activity, health and well-being observed in the East Village group compared with controls and the influence of specific elements of the built environment on observed changes. The ENABLE London project exploits a unique opportunity to evaluate a 'natural experiment', provided by the building and rapid occupation of East Village. Findings from the study will be generalisable to other urban residential housing developments, and will help inform future evidence-based urban planning

    A report on the piloting of a novel computer-based medical case simulation for teaching and formative assessment of diagnostic laboratory testing

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    Objectives: Insufficient attention has been given to how information from computer-based clinical case simulations is presented, collected, and scored. Research is needed on how best to design such simulations to acquire valid performance assessment data that can act as useful feedback for educational applications. This report describes a study of a new simulation format with design features aimed at improving both its formative assessment feedback and educational function. Methods: Case simulation software (LabCAPS) was developed to target a highly focused and well-defined measurement goal with a response format that allowed objective scoring. Data from an eight-case computer-based performance assessment administered in a pilot study to 13 second-year medical students was analyzed using classical test theory and generalizability analysis. In addition, a similar analysis was conducted on an administration in a less controlled setting, but to a much large sample (n=143), within a clinical course that utilized two random case subsets from a library of 18 cases. Results: Classical test theory case-level item analysis of the pilot assessment yielded an average case discrimination of 0.37, and all eight cases were positively discriminating (range=0.11–0.56). Classical test theory coefficient alpha and the decision study showed the eight-case performance assessment to have an observed reliability of σ=G=0.70. The decision study further demonstrated that a G=0.80 could be attained with approximately 3 h and 15 min of testing. The less-controlled educational application within a large medical class produced a somewhat lower reliability for eight cases (G=0.53). Students gave high ratings to the logic of the simulation interface, its educational value, and to the fidelity of the tasks. Conclusions: LabCAPS software shows the potential to provide formative assessment of medical students’ skill at diagnostic test ordering and to provide valid feedback to learners. The perceived fidelity of the performance tasks and the statistical reliability findings support the validity of using the automated scores for formative assessment and learning. LabCAPS cases appear well designed for use as a scored assignment, for stimulating discussions in small group educational settings, for self-assessment, and for independent learning. Extension of the more highly controlled pilot assessment study with a larger sample will be needed to confirm its reliability in other assessment applications
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