Scavenger receptors (SRs) are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

The LeucoPatch device uses bedside centrifugation without additional reagents to generate a disc comprising autologous leucocytes, platelets, and fibrin, which is applied to the surface of the wound. We aimed to test the effectiveness of LeucoPatch on the healing of hard-to-heal foot ulcers in people with diabetes. This was a multicentre, international, observer-masked, randomised controlled trial of people with diabetes and a hard-to-heal foot ulcer done in 32 specialist diabetic foot clinics in three countries (UK, Denmark, and Sweden). After a 4-week run-in period, those with a reduction in ulcer area of less than 50% were randomly allocated (1:1) by computer-generated, web-based randomisation (block sizes of two, four, and six) to either prespecified good standard care alone or care plus weekly application of LeucoPatch. The primary outcome was the proportion of ulcers that healed within 20 weeks assessed in the intention-to-treat population (all participants with post-randomisation data collected), defined as complete epithelialisation (confirmed by an observer who was masked to randomisation group), and remained healed for 4 weeks. This trial is registered with the ISRCTN registry, number 27665670, and ClinicalTrials.gov, number NCT02224742. Between Aug 30, 2013, and May 3, 2017, 269 participants were randomly allocated to receive treatment (137 to receive standard care and 132 to receive LeucoPatch). The mean age was 61·9 years (SD 11·6), 217 (82%) were men, and 222 (83%) had type 2 diabetes. In the LeucoPatch group, 45 (34%) of 132 ulcers healed within 20 weeks versus 29 (22%) of 134 ulcers in the standard care group (odds ratio 1·58, 96% CI 1·04-2·40; p=0·0235) by intention-to-treat analysis. Time to healing was shorter in the LeucoPatch group (p=0·0246) than in the standard care group. No difference in adverse events was seen between the groups. The most common serious adverse event (SAE) was diabetic foot infection (24 events in the LeucoPatch group [24% of all SAEs] and 20 in the standard care group [27% of all SAEs]. There were no device-related adverse events. The use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes. Reapplix ApS.

Peripheral arterial disease (PAD) is a common vascular condition that affects both quality of life and life expectancy with an increased risk of cardiovascular events. A literature search was carried out of Pub-Med, MEDLINE, the Cochrane Library and Google Scholar from the establishment of these databases up to February 2012. The search was performed by using the keywords ‘peripheral arterial disease’ and one of the following words: ‘management’, ‘investigations’, ‘risk factors’, ‘epidemiology’, ‘revascularization’, ‘cryoplasty’, ‘atherectomy’ and ‘gene therapy’. Studies were limited to those published in English language. Aggressive risk factors modification is needed to reduce cardiovascular-related mortality in PAD patients. Choice of endovascular or surgical intervention remains controversial in an ever-evolving field. There is a rapid expansion of endovascular technologies aiming to improve the effectiveness of this modality. The advances in the fields of gene therapy and therapeutic angiogenesis mean these are potential future treatments. Tissue engineering is a developing area and aims to produce grafts with similar patency and infection profiles to those of autologous material. Further elucidation of the pathophysiology of atherosclerosis is required to provide new targets for pharmacotherapy.

Cardiovascular disease remains the main cause of mortality in individuals with diabetes mellitus (DM) and also results in significant morbidity. Premature and more aggressive atherosclerotic disease, coupled with an enhanced thrombotic environment, contributes to the high vascular risk in individuals with DM. This prothrombotic milieu is due to increased platelet activity together with impaired fibrinolysis secondary to quantitative and qualitative changes in coagulation factors. However, management strategies to reduce thrombosis risk remain largely similar in individuals with and without DM. The current review covers the latest in the field of antithrombotic management in DM. The role of primary vascular prevention is discussed together with options for secondary prevention following an ischaemic event in different clinical scenarios including coronary, cerebrovascular, and peripheral artery diseases. Antiplatelet therapy combinations as well as combination of antiplatelet and anticoagulant agents are examined in both the acute phase and long term, including management of individuals with sinus rhythm and those with atrial fibrillation. The difficulties in tailoring therapy according to the variable atherothrombotic risk in different individuals are emphasized, in addition to the varying risk within an individual secondary to DM duration, presence of complications and predisposition to bleeding events. This review provides the reader with an up-to-date guide for antithrombotic management of individuals with DM and highlights gaps in knowledge that represent areas for future research, aiming to improve clinical outcome in this high-risk population.

Objective: This work aims to develop an integrated in-shoe measurement system to fully record plantar loading, including both pressure and shear stresses, across the full contact surface. These data are vital to help understand and prevent the development of complex conditions such as Diabetic Foot Ulcers (DFUs), a worldwide healthcare challenge. Currently no systems exist to reliably record these data. Methods: In this paper we report development of the SLIPS (‘Shear Load Inductive Plantar Sensing’) system which integrates 64 tri-axial force sensors into a flexible insole to measure plantar loading. SLIPS translates our multi-axis inductive load sensing technology into a full sensory array embedded within an insole and complete with communication and power bus. A pilot study evaluates the system in three healthy participants during walking. Results: Testing shows that the SLIPS system is well tolerated by participants and can operate under dynamic gait loading regimes. The pilot study reveals the complex nature of plantar loading. Regions of peak pressure loading align with anatomical landmarks and shear loading forms a significant component of the overall load. Notably, regions of peak shear and pressure are not necessarily collocated or present in unison. Conclusion: This work highlights the need for in-shoe plantar measurement systems like SLIPS capable of mapping both pressure and shear load, and their use to improve understanding of how these factors relate to clinical conditions like DFU. Significance: SLIPS represents the first in-shoe measurement system capable of measuring both pressure and shear across the whole plantar surface in unison.

Diabetic foot ulcers (DFUs) are a severe global public health issue. Plantar normal and shear load are believed to play an important role in the development of foot ulcers and could be a valuable indicator to improve assessment of DFUs. However, despite their promise, plantar load measurements currently have limited clinical application, primarily due to the lack of reliable measurement techniques particularly for shear load measurements. In this paper we report on the design and evaluation of a novel tri-axis force sensor to measure both normal and shear load on the foot’s plantar surface simultaneously. The sensor consists of a group of inductive sensing coils above which a conductive target is placed on a hyperelastic elastomer. Movement of the target under load affects the coil inductances which are measured and digitized by an embedded system. Using a computational finite element model, we investigated the influence of sensing coil form and configuration on sensor performance. A sensor configured with four-square coils and maximal turns provided the best performance for plantar load measurements. A prototype was fabricated and calibrated using a neural network to map the non-linear relationship between the sensor output and the applied tri-axis load. Experimental evaluation indicates that the tri-axis sensor can effectively detect shear load of ±16 N and normal load up to 105 N (RMS errors: 1.05 N and 1.73 N respectively) with a high performance. Overall, this sensor provides a promising basis for plantar normal and shear load measurement which are crucial for improved assessment of DFU.