Oral health and pathology: a macrophage account.

Macrophages are present in healthy oral mucosa and their numbers increase dramatically during disease. They can exhibit a diverse range of phenotypes characterised as a functional spectrum from pro-inflammatory to anti-inflammatory (regulatory) subsets. This review illustrates the role of these subsets in the oral inflammatory disease lichen planus, and the immunosuppressive disease oral squamous cell carcinoma (SCC). We conclude that the role of macrophages in driving progression in oral disease identifies them as potential therapeutic targets for a range of oral pathologies

Restenosis and its determinants in first and repeat coronary angioplasty

Restenosis is the main problem limiting long-term success of percutaneous transluminal coronary angioplasty (PTCA) and is most accurately evaluated by follow-up angiography. We compared the primary and long-term results of angioplasty in 268 consecutive patients (293 segments) with first PTCA (PTCA 1, angiographic follow-up 98%) and in 66 patients (76 segments) with repeat PTCA after restenosis (PTCA 2, angiographic follow-up 92%). Forty clinical, angiographic and procedural factors were assessed in relation to outcome. Primary success rate was higher in PTCA 2 (91% vs 67.5%) and major complications were fewer (4.5% vs 16%).Higher inflation pressure (7.9 ± 2.3 vs 6.8 ± 1.8 atm, P70%) after PTCA 1 and after PTC A 2 (27% vs 36%, P = NS) and the mean time to recurrence (4.7 vs 5.3 months, P = NS) were similar. Procedural factors were the main determinants of long-term success in primary PTCA. The restenosis risk was independently related to residual stenosis >45% (P<0.001), variant angina (P<0.05) and multivessel disease (P<0.05) after PTCA 1 and to male sex (P<0.001) and higher inflation pressure (P<0.05) after PTCA 2. Mild to moderate intimal tearing was associated with less restenosis after PTC A 1, but not after PTCA 2. Including 9 patients (10 segments) with a third PTCA, 70% of the 66 patients with repeat PTCA had a successful long-term outcome. Repeat angioplasty should therefore be considered as an integral part of PTCA therapy. Restenosis however remains a major concern. An optimal primary result with a minimal residual stenosis is decisive for first PTCA, whereas avoidance of a dissection by using lower inflation pressure on a restenosis might improve the long-term outcome of repeat PTC

Relationship between MRI Derived Right Ventricular Mass and Left Ventricular Involvement in Patients with Anderson-Fabry Disease

Poster presentationpublished_or_final_versio

STORMTOOLS: Coastal Environmental Risk Index (CERI)

One of the challenges facing coastal zone managers and municipal planners is the development of an objective, quantitative assessment of the risk to structures, infrastructure, and public safety that coastal communities face from storm surge in the presence of changing climatic conditions, particularly sea level rise and coastal erosion. Here we use state of the art modeling tool (ADCIRC and STWAVE) to predict storm surge and wave, combined with shoreline change maps (erosion), and damage functions to construct a Coastal Environmental Risk Index (CERI). Access to the state emergency data base (E-911) provides information on structure characteristics and the ability to perform analyses for individual structures. CERI has been designed as an on line Geographic Information System (GIS) based tool, and hence is fully compatible with current flooding maps, including those from FEMA. The basic framework and associated GIS methods can be readily applied to any coastal area. The approach can be used by local and state planners to objectively evaluate different policy options for effectiveness and cost/benefit. In this study, CERI is applied to RI two communities; Charlestown representing a typical coastal barrier system directly exposed to ocean waves and high erosion rates, with predominantly low density single family residences and Warwick located within Narragansett Bay, with more limited wave exposure, lower erosion rates, and higher residential housing density. Results of these applications are highlighted herein

Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease

published_or_final_versio

Near-infrared monitoring of roller compacted ribbon density: investigating sources of variation contributing to noisy spectral data

The aim of this study was to highlight how variability in roller compacted ribbon quality can impact on NIR spectral measurement and to propose a simple method of data selection to remove erroneous spectra. The use of NIR spectroscopy for monitoring ribbon envelope density has been previously demonstrated, however to date there has been limited discussion as to how spectral data sets can contain erroneous outliers due to poor sample presentation to the NIR probes. In this study compacted ribbon of variable quality was produced from three separate blends of microcrystalline cellulose (MCC)/lactose/magnesium stearate at 8 Roll Force settings (2–16 kN/cm). The three blends differed only in the storage conditions of MCC prior to blending and compaction. MCC sublots were stored at ambient (41% RH/20 °C), low humidity (11% RH/20 °C) and high humidity (75% RH/40 °C) conditions prior to blending. Ribbon envelope density was measured and ribbon NIR spectral data was acquired at line using a multi-probe spectrometer (MultiEye™ NIR). Initial inspection of the at-line NIR spectral data set showed a large degree of variability which indicated that some form of data cleaning was required. The source of variability in spectral measurements was investigated by subjective visual examination and by statistical analysis. Spectral variability was noted due to the storage conditions of MCC prior to compaction, Roll Force settings and between individual ribbon samples sampled at a set Roll Force/Blend combination. Variability was also caused by ribbon presentation to probes, such as differences in the presentation of broken, curved and flat intact ribbons. Based on the subjective visual examination of data, a Visual Discard method was applied and was found to be particularly successful for blends containing MCC stored at ambient and low humidity. However the Visual Discard method of spectra cleaning is subjective and therefore a non-subjective method capable of screening for erroneous probe readings was developed. For this data set a Trimmed Mean method was applied to set a limit on how data is cleaned from the data set allowing for the removal of a faulty probe reading (25% of data) or a poor sample (33% of data). The 33% Trimmed Mean reduced the impact of spectral variation or misreads between samples or probes and was found to be as successful as the Visual Discard method at cleaning the data set prior to development of the calibration equation

In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation

Drug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus. However, it is not clear if the observed enhanced in vitro dissolution can forecast drug bioavailability in vivo. In this study, the ability of different in vitro dissolution models to predict in vivo oral bioavailability in a pig model was examined. The fenofibrate-loaded mesoporous silica formulation was compared directly to a commercial reference product, Lipantil Supra®. Three in vitro dissolution methods were considered; USP Type II (paddle) apparatus, USP Type IV (flow-through cell) apparatus and a USP IV Transfer model (incorporating a SGF to FaSSIF-V2 media transfer). In silico modelling, using a physiologically based pharmacokinetic modelling and simulation software package (Gastroplus™), to generate in vitro/in vivo relationships was also investigated. The study demonstrates that the in vitro dissolution performance of a mesoporous silica formulation varies depending on the dissolution apparatus utilised and experimental design. The findings show that the USP IV transfer model was the best predictor of in vivo bioavailability. The USP Type II (paddle) apparatus was not effective at forecasting in vivo behaviour. This observation is likely due to hydrodynamic differences between the two apparatus and the ability of the transfer model to better simulate gastrointestinal transit. The transfer model is advantageous in forecasting in vivo behaviour for formulations which promote drug supersaturation and as a result are prone to precipitation to a more energetically favourable, less soluble form. The USP IV transfer model could prove useful in future mesoporous silica formulation development. In silico modelling has the potential to assist in this process. However, further investigation is required to overcome the limitations of the model for solubility enhancing formulations

Diffusion of e-health innovations in 'post-conflict' settings: a qualitative study on the personal experiences of health workers.

BACKGROUND: Technological innovations have the potential to strengthen human resources for health and improve access and quality of care in challenging 'post-conflict' contexts. However, analyses on the adoption of technology for health (that is, 'e-health') and whether and how e-health can strengthen a health workforce in these settings have been limited so far. This study explores the personal experiences of health workers using e-health innovations in selected post-conflict situations. METHODS: This study had a cross-sectional qualitative design. Telephone interviews were conducted with 12 health workers, from a variety of cadres and stages in their careers, from four post-conflict settings (Liberia, West Bank and Gaza, Sierra Leone and Somaliland) in 2012. Everett Roger's diffusion of innovation-decision model (that is, knowledge, persuasion, decision, implementation, contemplation) guided the thematic analysis. RESULTS: All health workers interviewed held positive perceptions of e-health, related to their beliefs that e-health can help them to access information and communicate with other health workers. However, understanding of the scope of e-health was generally limited, and often based on innovations that health workers have been introduced through by their international partners. Health workers reported a range of engagement with e-health innovations, mostly for communication (for example, email) and educational purposes (for example, online learning platforms). Poor, unreliable and unaffordable Internet was a commonly mentioned barrier to e-health use. Scaling-up existing e-health partnerships and innovations were suggested starting points to increase e-health innovation dissemination. CONCLUSIONS: Results from this study showed ICT based e-health innovations can relieve information and communication needs of health workers in post-conflict settings. However, more efforts and investments, preferably driven by healthcare workers within the post-conflict context, are needed to make e-health more widespread and sustainable. Increased awareness is necessary among health professionals, even among current e-health users, and physical and financial access barriers need to be addressed. Future e-health initiatives are likely to increase their impact if based on perceived health information needs of intended users

Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?

Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. Its expression is induced by a number of factors including TGF-β. It has been associated with fibrosis in various tissues including the kidney. Diabetic nephropathy (DN) develops in about 30% of patients with diabetes and is characterized by thickening of renal basement membranes, fibrosis in the glomerulus (glomerulosclerosis), tubular atrophy and interstitial fibrosis, all of which compromise kidney function. This review examines changes in CTGF expression in the kidney in DN, the effects they have on glomerular mesangial and podocyte cells and the tubulointerstitium, and how these contribute to driving fibrotic changes in the disease. CTGF can bind to several other growth factors modifying their function. CTGF is also able to interact with receptors on cells, including integrins, tyrosine receptor kinase A (TrkA), low density lipoprotein receptor-related protein (LRP) and heparan sulphate proteoglycans. These interactions, the intracellular signalling pathways they activate, and the cellular responses evoked are reviewed. CTGF also induces the expression of chemokines which themselves have pharmacological actions on cells. CTGF may prompt some responses by acting through several different mechanisms, possibly simultaneously. For example, CTGF is often described as an effector of TGF-β. It can promote TGF-β signalling by binding directly to the growth factor, promoting its interaction with the TGF-β receptor; by triggering intracellular signalling on binding the TrkA receptor, which leads to the transcriptional repression of Smad7, an inhibitor of the TGF-β signalling pathway; and by binding to BMP-7 whose own signalling pathway opposing TGF-β is inhibited, leading to enhanced TGF-β signalling