Pilot study in human healthy volunteers on the use of magnetohydrodynamics in needle-free continuous glucose monitoring

The benefits of continuous glucose monitoring (CGM) in diabetes management are extensively documented. Yet, the broader adoption of CGM systems is limited by their cost and invasiveness. Current CGM devices, requiring implantation or the use of hypodermic needles, fail to offer a convenient solution. We have demonstrated that magnetohydrodynamics (MHD) is effective at extracting dermal interstitial fluid (ISF) containing glucose, without the use of needles. Here we present the first study of ISF sampling with MHD for glucose monitoring in humans. We conducted 10 glucose tolerance tests on 5 healthy volunteers and obtained a significant correlation between the concentration of glucose in ISF samples extracted with MHD and capillary blood glucose samples. Upon calibration and time lag removal, the data indicate a Mean Absolute Relative Difference (MARD) of 12.9% and Precision Absolute Relative Difference of 13.1%. In view of these results, we discuss the potential value and limitations of MHD in needle-free glucose monitoring.Peer reviewe

Wound healing, a multidisciplinary approach: combining mathematical models and biological experiments

Cutaneous wound repair occurs as a continuous process in both space and time; however, studies of healing mechanisms and outcomes frequently generate spatially and temporally sparse datasets. We propose a range of techniques that allow the size, cellular processes and scar tissue properties of wounds to be measured and predicted at high spatial and temporal resolution. A non-invasive wound imaging system is shown to provide reliable measurements of wound diameter, perimeter and surface area, but is less reliable in producing 3D metrics such as volume and depth. Wound size and time post healing have a combined effect on reliability, with more reliable measurements obtained at earlier timepoints. A semi-automated pipeline is found to be appropriate for determining the cellular composition of the wound space, but cannot be applied to areas of healthy epidermis due to the close packing of keratinocytes. A range of mathematical models are employed to predict cell numbers within the wound space. An extended domain, partial differential equation model with spatial control of cell proliferation and migration is found to best recapitulate the cellular dynamics observed in vivo. However, if epidermal stratification is to be incorporated, an agent-based description may be preferable. Finally, we formulate a model system that can predict the alignment of collagen fibres and fibroblasts over continuous orientation space. Parameter sets that include large shear forces (which may result from elongated wound geometries or interventions such as suturing) can produce skewed distributions of orientation that cannot be established using discontinuous approaches. Together, this suite of computational approaches provides a powerful set of tools with which the mechanisms of cutaneous wound healing can be investigated, quantified and elucidated

Mobile Measurement system for clinical diagnosis: A Transepidermal Water Loss Probe

Transepidermal water loss (TEWL) is commonly used as a surrogate marker for skin barrier function. Although current devices enable TEWL to be measured with ease and precision under controlled laboratory conditions, they do not yield reliable readings in an uncontrolled environment. This project aimed to develop a new TEWL device that is mobile, i.e. that would fit in the pocket and measure TEWL anywhere. For this, the prototype had to be portable, wireless and to have good autonomy. In addition the prototype performances were evaluated in terms of repeatability and sensitivity. The primary design is based on a closed-chamber to limit the effect of the environment. Moreover, the use of a fan to remove surface water and homogenise the micro-climate in the chamber was introduced. Mathematical modelling and measurements of water vapour and heat flux in closed TEWL chambers of a range of geometries was investigated to establish ideal sensors locations and blower flow rates. It was found that the fan decreased repeatability but increased sensitivity. In addition, it decreased coefficient of variation of measurements on moist skin, contrary to other TEWL chamber methods. Furthermore, lower fan speed yielded better precision. Finally, the gradient calculation is the crucial part of a TEWL measurement and Least Square Fitting was used to stabilise the readings and improve repeatability at the expense of computational speed. The work suggests that it should be possible to develop a viable new design that can generate measurements in the field that are easy to make and reliable but further work is needed to establish accuracy evaluation from a calibration with a fixed quantity of water and to develop a full commercial product

PPARs as Key Mediators of Metabolic and Inflammatory Regulation

Mounting evidence suggests a bidirectional relationship between metabolism and inflammation. Molecular crosstalk between these processes occurs at different levels with the participation of nuclear receptors, including peroxisome proliferator-activated receptors (PPARs). There are three PPAR isotypes, α, β/δ, and γ, which modulate metabolic and inflammatory pathways, making them key for the control of cellular, organ, and systemic processes. PPAR activity is governed by fatty acids and fatty acid derivatives, and by drugs used in clinics (glitazones and fibrates). The study of PPAR action, also modulated by post-translational modifications, has enabled extraordinary advances in the understanding of the multifaceted roles of these receptors in metabolism, energy homeostasis, and inflammation both in health and disease. This Special Issue of IJMS includes a broad range of basic and translational article, both original research and reviews, focused on the latest developments in the regulation of metabolic and/or inflammatory processes by PPARs in all organs and the microbiomes of different vertebrate species

Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes

Cells and Materials for Disease Modeling and Regenerative Medicine

Materials science and engineering are strongly developing tools with increasing impact in the biotechnological and biomedical areas. Interestingly, research in molecular and cellular biology is often at the core of the design and development of materials-based approaches, providing biological rationale. Focused on research relying on biology–materials interaction, IJMS launched a Special Issue named “Cells and Materials for Disease Modeling and Regenerative Medicine”. The aim of the Special Issue was to generate a compilation of in vitro and in vivo strategies based on cell–material interactions. This book compiles the papers published in that Special Issue and includes a selection of six original scientific experimental articles and six comprehensive reviews. We are convinced that this collection of articles shows representative examples of the state of the art in the field, unveiling the relevance of materials research in generating new regenerative medicine and disease modeling approaches

The effects of VEGF overexpression on the utero-placental circulation

Impaired uterine blood flow (UBF) leads to fetal growth restriction (FGR), one of the most challenging obstetric complications. FGR is associated with stillbirth, long-term neurological impairment and adult onset cardiovascular disease; there is no treatment currently available. Previously, it was shown that sustained local over-expression of Vascular Endothelial Growth Factor (VEGF) in the uterine arteries (UAs) of pregnant sheep using an adenoviral vector results in increased UBF as measured by Doppler sonography, reduced vascular contractility and increased vascular relaxation 4-7 days after administration. The aim of this thesis is to examine the long-term effects on UBF, UA vascular reactivity, and the possible mechanism of action. Telemetric transit-time flow probes were implanted around the UAs of mid-gestation pregnant sheep (n=10), and a telemetric blood-pressure sensitive catheter was inserted in the maternal (n=5) or fetal (n=4) carotid arteries. After obtaining baseline values for 7 days, we injected adenovirus vectors (5x1011 particles) encoding the VEGF-A165 gene (Ad.VEGF) into one UA, and a reporter β-galactosidase gene (Ad.LacZ), contra-laterally. UBF and maternal haemodynamics were measured daily until term, when the UAs were harvested and their vascular reactivity studied. There was a significant increase in UBF in the Ad.VEGF transduced side (36.53% v/s 20.08%, p=0.02), a reduction in UA contractility but no difference in relaxation. A significantly greater number of adventitial blood vessels were observed in the Ad.VEGF treated UA. There were no significant changes in maternal or fetal blood pressure post-injection. Similar effects were observed with injection of an adenovirus encoding another member of the VEGF gene family, VEGF-DΔNΔC (n=5). Endothelial cells (ECs) were isolated from the UAs of control midgestation pregnant sheep, cultured and infected with Ad.VEGF or Ad.LacZ vector. Protein extracted from UAECs infected ex vivo was assayed for eNOS and phosphorylated eNOS (Ser1177) levels by Western blotting. eNOS and phosphoeNOS levels increased with rising Ad.VEGF concentrations in UAECs; Ad.LacZ vector transduction had no effect. Local over-expression of VEGF effects a long-term increase in UBF by upregulation of eNOS, with neovascularization of the adventitia and reduced UA contractility. These changes may benefit pregnancies complicated by severe FGR. With clinical translation in mind, the last section of this thesis describes the optimization of a technique of gene targeting to the utero-placental circulation of growth-restricted guinea pigs, using a thermo-sensitive pluronic gel. Having optimized this technique, VEGF over-expression in the uteroplacental circulation is now being tested in this animal model of FGR

A Meeting of Minds: In Recognition of the Contributions of Randall J. Cohrs

A Special Issue in memory of Randall J. Cohrs, Ph.D. Topics include original research reports on a variety of viruses as well as reviews and commentaries on Randy’s contributions to many investigations