Wearable multimodal skin sensing for the diabetic foot

Ulceration of the diabetic foot is currently difficult to detect reliably in a timely manner causing undue suffering and cost. Current best practice is for daily monitoring by those living with diabetes coupled to scheduled monitoring by the incumbent care provider. Although some metrics have proven useful in the detection or prediction of ulceration, no single metric can currently be relied upon for diagnosis. We have developed a prototype multivariate extensible sensor platform with which we demonstrate the ability to gather acceleration, rotation, galvanic skin response, environmental temperature, humidity, force, skin temperature and bioimpedance signals in real time, for later analysis, utilising low cost Raspberry Pi and Arduino devices. We demonstrate the utility of the Raspberry Pi computer in research which is of particular interest to this issue of electronics - Raspberry Pi edition. We conclude that the hardware presented shows potential as an adaptable research tool capable of gathering synchronous data over multiple sensor modalities. This research tool will be utilised to optimise sensor selection, placement and algorithm development prior to translation into a sock, insole or platform diagnostic device at a later date. The combination of a number of clinically relevant parameters is expected to provide greater understanding of tissue state in the foot but requires further volunteer testing and analysis beyond the scope of this paper which will be reported in due course

Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG −394 bp 5′ to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

Microdialysis of large molecules

Microdialysis has been used in many tissues, including skin, brain, adipose tissue, muscle, kidney, and gastrointestinal tract, to recover low–molecular mass endogenous mediators, metabolites, and xenobiotics from the interstitial space. Recently, molecules of larger molecular mass, such as plasma proteins, cytokines, growth factors, and neuropeptides, have also been recovered successfully using larger-pore membranes. Microdialysis recovery of large molecules offers the opportunity to identify patterns of protein expression in a variety of tissue spaces and to evaluate clinically useful biomarkers of disease. From this may develop a better understanding of the disease process and its diagnosis and more targeted approaches to therapy.<br/

The microcirculation - a target for developmental priming.

There is increasing evidence that the early life environment, of which nutrition is a key component, acts through developmental adaptations to set the capacity of cardiovascular and metabolic pathways, and ultimately the limits to physiological challenges in later life. Sub-optimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity, which are strongly associated with later development of obesity, type 2 diabetes and hypertension. These conditions are also linked to microvascular rarefaction and remodeling that together limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates, and increase local and overall peripheral resistance. Changes in small vessel structure and function may be seen very early, long before the onset of overt cardiovascular and metabolic disease, and may thus be a target for early therapeutic and life style intervention strategies. This article explores how a disadvantageous microvascular phenotype may result from perinatal priming and how developmental plasticity may become an important and additional risk determinant in susceptibility to cardio-metabolic disease in adult life.<br/

An image based model of fluid flow through lymph nodes

The lymphatic system returns fluid to the blood stream from the tissues to maintain tissue fluid homeostasis. Lymph nodes distributed throughout the system filter the lymphatic fluid. The afferent and efferent lymph flow conditions of lymph nodes can be measured in experiments, however it is difficult to measure the flow within the nodes. In this paper we present an image based modelling approach to investigate how the internal structure of the node affects the fluid flow pathways within the node. Selective plane illumination microscopy images of murine lymph nodes are used to identify the geometry and structure of the tissue within the node and to determine the permeability of the lymph node interstitium to lymphatic fluid. Experimental data are used to determine boundary conditions and optimise the parameters for the model. The numerical simulations conducted within the model are implemented in COMSOL Multiphysics, a commercial finite element analysis software. The parameter fitting resulted in the estimate that the average permeability for lymph node tissue is of the order of magnitude of 10-11 m239 . Our modelling shows that the flow predominantly takes a direct path between the afferent and efferent lymphatics and that fluid is both filtered and absorbed across the blood vessel boundaries. The amount that is absorbed or extravasated in the model is dependent on the efferent lymphatic lumen fluid pressure

Modulation of microvascular function following low-dose exposure to the organophosphorous compound malathion in human skin in vivo

This study investigates whether malathion, a widely used organophosphate insecticide, has its effects on cutaneous vasculature in healthy human volunteers through its anticholinergic activity or through the modulation of other, noncholinergic pathways. Acute, low-dose exposure to malathion (10 mg/ml for 5 h under occlusive dressing) caused a significant increase in cutaneous blood flux, monitored by using laser-Doppler flowmetry and imaging. It had little effect on tissue levels of ACh, nitric oxide, and histamine assayed in dermal dialysate collected from malathion-exposed and control-treated skin. The duration of the cutaneous vascular response to exogenous ACh (2%) delivered by iontophoresis was significantly enhanced by preexposure to malathion, both &lt;1 h after its removal and 24 h later (P &lt; 0.001). At &lt;1 h, the time to 50% decay of the response was 24 ± 4 and 50 ± 8 min in control and malathion-treated skin, respectively. Malathion also enhanced the size and duration of the axon reflex-mediated vasoresponse to ACh. The increase in blood flux to malathion and the endothelium-mediated response to exogenous ACh, both in the presence and absence of malathion, were attenuated by pretreatment of the skin with atropine and local anesthesia (P &lt; 0.01). We conclude that short-term exposure to a single low dose of malathion causes prolonged modulation of the physiological function of the cutaneous vasculature and that this is, in part, through its action on acetylcholinesterase at both neuronal and nonneuronal sites