Collagen-hyaluronic acid scaffolds for adipose tissue engineering.

Three-dimensional (3-D) in vitro models of the mammary gland require a scaffold matrix that supports the development of adipose stroma within a robust freely permeable matrix. 3-D porous collagen-hyaluronic acid (HA: 7.5% and 15%) scaffolds were produced by controlled freeze-drying technique and crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride. All scaffolds displayed uniform, interconnected pore structure (total porosity approximately 85%). Physical and chemical analysis showed no signs of collagen denaturation during the formation process. The values of thermal characteristics indicated that crosslinking occurred and that its efficiency was enhanced by the presence of HA. Although the crosslinking reduced the swelling of the strut material in water, the collagen-HA matrix as a whole tended to swell more and show higher dissolution resistance than pure collagen samples. The compressive modulus and elastic collapse stress were higher for collagen-HA composites. All the scaffolds were shown to support the proliferation and differentiation 3T3-L1 preadipocytes while collagen-HA samples maintained a significantly increased proportion of cycling cells (Ki-67+). Furthermore, collagen-HA composites displayed significantly raised Adipsin gene expression with adipogenic culture supplementation for 8 days vs. control conditions. These results indicate that collagen-HA scaffolds may offer robust, freely permeable 3-D matrices that enhance mammary stromal tissue development in vitro.This was supported by the Biotechnology and Biological Sciences Research Council

The effect of CO2-loaded amine solvents on the corrosion of a carbon steel stripper

The corrosive behaviour of loaded amine solvents was evaluated under stripper operating conditions, for post-combustion carbon capture, to determine the feasibility of using carbon steel in plant construction. In addition to monoethanolamine, three alternative amine solvents: methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), 1-(2-aminoethyl)piperazine (AEPZ), and the common additive K2CO3 were studied when in contact with carbon steel (C1018) over a 28-day period. Corrosive behaviour was evaluated using carbon steel coupons: gravimetric method for weight change, surface imaging (SEM) and analytical techniques (EDX and XRD), and Fe ion concentration in solution (ICP–OES). The results demonstrated that MDEA and AMP as well as K2CO3 develop a significant siderite (FeCO3) layer on the carbon steel surface. The presence of this layer is attributed to the preferred reaction pathway with CO2 for tertiary and sterically hindered amines. The FeCO3 layer formed in the case of MDEA provides superior protection from continued corrosion of the carbon steel. By contrast, MEA and AEPZ show significant corrosion to the carbon steel surface. In conclusion, MDEA, AMP, and K2CO3 can preferentially produce sufficient surface FeCO3 layers to reduce corrosion levels in carbon steels for use under stripper conditions in post-combustion carbon capture plants

Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines

Cancer is characterized by cell heterogeneity and the development of 3D $\textit{in vitro }$ assays that can distinguish more invasive or migratory phenotypes could enhance diagnosis or drug discovery. 3D collagen scaffolds have been used to develop analogues of complex tissues $\textit{in vitro }$ and are suited to routine biochemical and immunological assays. We sought to increase 3D model tractability and modulate the migration rate of seeded cells using an ice-templating technique to create either directional/anisotropic or non-directional/isotropic porous architectures within cross-linked collagen scaffolds. Anisotropic scaffolds supported the enhanced migration of an invasive breast cancer cell line MDA-MB-231 with an altered spatial distribution of proliferative cells in contrast to invasive MDA-MB-468 and non-invasive MCF-7 cells lines. In addition, MDA-MB-468 showed increased migration upon epithelial-to-mesenchymal transition (EMT) in anisotropic scaffolds. The provision of controlled architecture in this system may act both to increase assay robustness and as a tuneable parameter to capture detection of a migrated population within a set time, with consequences for primary tumour migration analysis. The separation of invasive clones from a cancer biomass with in vitro platforms could enhance drug development and diagnosis testing by contributing assay metrics including migration rate, as well as modelling cell-cell and cell-matrix interaction in a system compatible with routine histopathological testing.The authors gratefully acknowledge the financial support of the ERC Advanced Grant 320598 3D-E and the Newton Trust. A.H. held a Daphne Jackson Fellowship funded by the University of Cambridge for part of the work. R.D.H. is funded through a NC3Rs studentship

GPAQ-R: development and psychometric properties of a version of the general practice assessment questionnaire for use for revalidation by general practitioners in the UK.

BACKGROUND: The General Practice Assessment Questionnaire (GPAQ) has been widely used to assess patient experience in general practice in the UK since 2004. In 2013, new regulations were introduced by the General Medical Council (GMC) requiring UK doctors to undertake periodic revalidation, which includes assessment of patient experience for individual doctors. We describe the development of a new version of GPAQ - GPAQ-R which addresses the GMC's requirements for revalidation as well as additional NHS requirements for surveys that GPs may need to carry out in their own practices. METHODS: Questionnaires were given out by doctors or practice staff after routine consultations in line with the guidance given by the General Medical Council for surveys to be used for revalidation. Data analysis and practice reports were provided independently. RESULTS: Data were analysed for questionnaires from 7258 patients relating to 164 GPs in 29 general practices. Levels of missing data were generally low (typically 4.5-6%). The number of returned questionnaires required to achieve reliability of 0.7 were around 35 for individual doctor communication items and 29 for a composite score based on doctor communication items. This suggests that the responses to GPAQ-R had similar reliability to the GMC's own questionnaire and we recommend 30 completed GPAQ-R questionnaires are sufficient for revalidation purposes. However, where an initial screen raises concern, the survey might be repeated with 50 completed questionnaires in order to increase reliability. CONCLUSIONS: GPAQ-R is a development of a well-established patient experience questionnaire used in general practice in the UK since 2004. This new version can be recommended for use in order to meet the UK General Medical Council's requirements for surveys to be used in revalidation of doctors. It also meets the needs of GPs to ask about patient experience relating to aspects of practice care that are not specific to individual general practitioners (e.g. receptionists, telephone access) which meet other survey requirements of the National Health Service in England. Use of GPAQ-R has the potential to reduce the number of surveys that GPs need to carry out in their practices to meet the various regulatory requirements which they face

Multiple goals and time constraints: perceived impact on physicians\u27 performance of evidence-based behaviours

Background: Behavioural approaches to knowledge translation inform interventions to improve healthcare. However, such approaches often focus on a single behaviour without considering that health professionals perform multiple behaviours in pursuit of multiple goals in a given clinical context. In resource-limited consultations, performing these other goal-directed behaviours may influence optimal performance of a particular evidence-based behaviour. This study aimed to investigate whether a multiple goal-directed behaviour perspective might inform implementation research beyond single-behaviour approaches.Methods: We conducted theory-based semi-structured interviews with 12 general medical practitioners (GPs) in Scotland on their views regarding two focal clinical behaviours-providing physical activity (PA) advice and prescribing to reduce blood pressure (BP) to < 140/80 mmHg-in consultations with patients with diabetes and persistent hypertension. Theory-based constructs investigated were: intention and control beliefs from the theory of planned behaviour, and perceived interfering and facilitating influence of other goal-directed behaviours performed in a diabetes consultation. We coded interview content into pre-specified theory-based constructs and organised codes into themes within each construct using thematic analysis. Results: Most GPs reported strong intention to prescribe to reduce BP but expressed reasons why they would not. Intention to provide PA advice was variable. Most GPs reported that time constraints and patient preference detrimentally affected their control over providing PA advice and prescribing to reduce BP, respectively. Most GPs perceived many of their other goal-directed behaviours as interfering with providing PA advice, while fewer GPs reported goal-directed behaviours that interfere with prescribing to reduce BP. Providing PA advice and prescribing to reduce BP were perceived to be facilitated by similar diabetes-related behaviours (e. g., discussing cholesterol). While providing PA advice was perceived to be mainly facilitated by providing other lifestyle-related clinical advice (e. g., talking about weight), BP prescribing was reported as facilitated by pursuing ongoing standard consultation-related goals (e. g., clearly structuring the consultation). Conclusion: GPs readily relate their other goal-directed behaviours with having a facilitating and interfering influence on their performance of particular evidence-based behaviours. This may have implications for advancing the theoretical development of behavioural approaches to implementation research beyond single-behaviour models

Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury

West CR, Goosey-Tolfrey VL, Campbell IG, Romer LM. Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury. J Appl Physiol 117: 36–45, 2014. First published May 22, 2014; doi:10.1152/japplphysiol.00218.2014.—We asked whether elastic binding of the abdomen influences respiratory mechanics during wheelchair propulsion in athletes with cervical spinal cord injury (SCI). Eight Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) performed submaximal and maximal incremental exercise tests on a treadmill, both with and without abdominal binding. Measurements included pulmonary function, pressure-derived indices of respiratory mechanics, operating lung volumes, tidal flow-volume data, gas exchange, blood lactate, and symptoms. Residual volume and functional residual capacity were reduced with binding (77 18 and 81 11% of unbound, P 0.05), vital capacity was increased (114 9%, P 0.05), whereas total lung capacity was relatively well preserved (99 5%). During exercise, binding introduced a passive increase in transdiaphragmatic pressure, due primarily to an increase in gastric pressure. Active pressures during inspiration were similar across conditions. A sudden, sustained rise in operating lung volumes was evident in the unbound condition, and these volumes were shifted downward with binding. Expiratory flow limitation did not occur in any subject and there was substantial reserve to increase flow and volume in both conditions. V ˙ O2 was elevated with binding during the final stages of exercise (8 –12%, P 0.05), whereas blood lactate concentration was reduced (16 –19%, P 0.05). V ˙ O2/heart rate slopes were less steep with binding (62 35 vs. 47 24 ml/beat, P 0.05). Ventilation, symptoms, and work rates were similar across conditions. The results suggest that abdominal binding shifts tidal breathing to lower lung volumes without influencing flow limitation, symptoms, or exercise tolerance. Changes in respiratory mechanics with binding may benefit O2 transport capacity by an improvement in central circulatory function.This article has been made available through the Brunel Open Access Publishing Fund

Approximation for Cooperative Interactions of a Spatially-Detailed Cardiac Sarcomere Model

We developed a novel ordinary differential equation (ODE) model, which produced results that correlated well with the Monte Carlo (MC) simulation when applied to a spatially-detailed model of the cardiac sarcomere. Configuration of the novel ODE model was based on the Ising model of myofilaments, with the “co-operative activation” effect introduced to incorporate nearest-neighbor interactions. First, a set of parameters was estimated using arbitrary Ca transient data to reproduce the combinational probability for the states of three consecutive regulatory units, using single unit probabilities for central and neighboring units in the MC simulation. The parameter set thus obtained enabled the calculation of the state transition of each unit using the ODE model with reference to the neighboring states. The present ODE model not only provided good agreement with the MC simulation results but was also capable of reproducing a wide range of experimental results under both steady-state and dynamic conditions including shortening twitch. The simulation results suggested that the nearest-neighbor interaction is a reasonable approximation of the cooperativity based on end-to-end interactions. Utilizing the modified ODE model resulted in a reduction in computational costs but maintained spatial integrity and co-operative effects, making it a powerful tool in cardiac modeling

Cotrimoxazole for childhood febrile illness in Malaria-endemic regions

The efficacy of co-trimoxozole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P. falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mglkg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Next-to-leading order predictions for Z gamma+jet and Z gamma gamma final states at the LHC

We present next-to-leading order predictions for final states containing leptons produced through the decay of a Z boson in association with either a photon and a jet, or a pair of photons. The effect of photon radiation from the final state leptons is included and we also allow for contributions arising from fragmentation processes. Phenomenological studies are presented for the LHC in the case of final states containing charged leptons and in the case of neutrinos. We also use the procedure introduced by Stewart and Tackmann to provide a reliable estimate of the scale uncertainty inherent in our theoretical calculations of jet-binned Z gamma cross sections. These computations have been implemented in the public code MCFM.Comment: 30 pages, 10 figure