Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5-year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular assessment, and infection and glycemic control. These practices are best coordinated by a multidisciplinary diabetic foot wound clinic. Even with this comprehensive approach, there is still room for improvement in DFU outcomes. Several adjuvant therapies have been studied to reduce DFU healing times and amputation rates. We reviewed the rationale and guidelines for current standard of care practices and reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies reviewed include the following categories: nonsurgical debridement agents, dressings and topical agents, oxygen therapies, negative pressure wound therapy, acellular bioproducts, human growth factors, energy-based therapies, and systemic therapies. Many of these agents have been found to be beneficial in improving wound healing rates, although a large proportion of the data are small, randomized controlled trials with high risks of bias.

/pdf/update-on-management-of-diabetic-foot-ulcers-3t7shn41st.pdf

Update on management of diabetic foot ulcers.

Advanced drug delivery systems and artificial skin grafts for skin wound healing.

Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.

/pdf/mesenchymal-stem-cells-improve-healing-of-diabetic-foot-2a0guadwpm.pdf

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer.

Lucilia Robineau-Desvoidy (Diptera: Calliphoridae) is a blow fly genus of forensic, medical, veterinary, and agricultural importance. This genus is also famous because of its beneficial uses in maggot debridement therapy (MDT). Although the genus is of considerable economic importance, our knowledge about microbes associated with these flies and how these bacteria are horizontally and trans-generationally transmitted is limited. In this study, we characterized bacteria associated with different life stages of Lucilia sericata (Meigen) and Lucilia cuprina (Wiedemann) and in the salivary gland of L. sericata by using 16S rDNA 454 pyrosequencing. Bacteria associated with the salivary gland of L. sericata were also characterized using light and transmission electron microscopy (TEM). Results from this study suggest that the majority of bacteria associated with these flies belong to phyla Proteobacteria, Firmicutes, and Bacteroidetes, and most bacteria are maintained intragenerationally, with a considerable degree of turnover from generation to generation. In both species, second-generation eggs exhibited the highest bacterial phylum diversity (20 % genetic distance) than other life stages. The Lucilia sister species shared the majority of their classified genera. Of the shared bacterial genera, Providencia, Ignatzschineria, Lactobacillus, Lactococcus, Vagococcus, Morganella, and Myroides were present at relatively high abundances. Lactobacillus, Proteus, Diaphorobacter, and Morganella were the dominant bacterial genera associated with a survey of the salivary gland of L. sericata. TEM analysis showed a sparse distribution of both Gram-positive and Gram-negative bacteria in the salivary gland of L. sericata. There was more evidence for horizontal transmission of bacteria than there was for trans-generational inheritance. Several pathogenic genera were either amplified or reduced by the larval feeding on decomposing liver as a resource. Overall, this study provides information on bacterial communities associated with different life stages of Lucilia and their horizontal and trans-generational transmission, which may help in the development of better vector-borne disease management and MDT methods.

/pdf/a-metagenomic-assessment-of-the-bacteria-associated-with-3z38jxvznr.pdf

A metagenomic assessment of the bacteria associated with Lucilia sericata and Lucilia cuprina (Diptera: Calliphoridae).

To highlight how gene drives could be useful for control of agricultural insect pests, we selected species that are pests of animals (New World screwworm), plants (spotted wing Drosophila, ...

https://www.tandfonline.com/doi/pdf/10.1080/23299460.2017.1410343

Agricultural production: assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest control

Transgenic sexing system for genetic control of the Australian sheep blow fly Lucilia cuprina.

Diabetes and its concurrent complications impact a significant proportion of the population of the US and create a large financial burden on the American health care system. FDA-approved maggot debridement therapy (MDT), the application of sterile laboratory-reared Lucilia sericata (green bottle fly) larvae to wounds, is a cost-effective and successful treatment for diabetic foot ulcers and other medical conditions. Human platelet derived growth factor-BB (PDGF-BB) is a secreted dimeric peptide growth factor that binds the PDGF receptor. PDGF-BB stimulates cell proliferation and survival, promotes wound healing, and has been investigated as a possible topical treatment for non-healing wounds. Genetic engineering has allowed for expression and secretion of human growth factors and other proteins in transgenic insects. Here, we present a novel concept in MDT technology that combines the established benefits of MDT with the power of genetic engineering to promote healing. The focus of this study is to create and characterize strains of transgenic L. sericata that express and secrete PDGF-BB at detectable levels in adult hemolymph, whole larval lysate, and maggot excretions/ secretions (ES), with potential for clinical utility in wound healing. We have engineered and confirmed transgene insertion in several strains of L. sericata that express human PDGF-BB. Using a heat-inducible promoter to control the pdgf-b gene, pdgf-b mRNA was detected via semi-quantitative PCR upon heat shock. PDGF-BB protein was also detectable in larval lysates and adult hemolymph but not larval ES. An alternative, tetracycline-repressible pdgf-b system mediated expression of pdgf-b mRNA when maggots were raised on diet that lacked tetracycline. Further, PDGF-BB protein was readily detected in whole larval lysate as well as larval ES. Here we show robust, inducible expression and production of human PDGF-BB protein from two conditional expression systems in transgenic L. sericata larvae. The tetracycline-repressible system appears to be the most promising as PDGF-BB protein was detectable in larval ES following induction. Our system could potentially be used to deliver a variety of growth factors and anti-microbial peptides to the wound environment with the aim of enhancing wound healing, thereby improving patient outcome in a cost-effective manner.

/pdf/towards-next-generation-maggot-debridement-therapy-vy6gfbfgcn.pdf

Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor.

The parasitic mite Varroa destructor Anderson & Trueman (Acari: Varroidae) has plagued European honey bees, Apis mellifera L. (Hymenoptera: Apidae), in the Americas since its introduction in the 1980s. For many years, these mites were sufficiently controlled using synthetic acaricides. Recently, however, beekeepers have experienced increased resistance by mites to chemical pesticides, which are also known to leave residues in hive products such as wax and honey. Thus there has been increased emphasis on nonchemical integrated pest management control tactics for Varroa. Because mites preferentially reproduce in drone brood (pupal males), we developed a treatment strategy focusing on salvaging parasitized drones while removing mites from them. We removed drone brood from colonies in which there was no acaricidal application and banked them in separate "drone-brood receiving" colonies treated with pesticides to kill mites emerging with drones. We tested 20 colonies divided into three groups: 1) negative control (no mite treatment), 2) positive control (treatment with acaricides), and 3) drone-brood removal and placement into drone-brood receiving colonies. We found that drone-brood trapping significantly lowered mite numbers during the early months of the season, eliminating the need for additional control measures in the spring. However, mite levels in the drone-brood removal group increased later in the summer, suggesting that this benefit does not persist throughout the entire season. Our results suggest that this method of drone-brood trapping can be used as an element of an integrated control strategy to control varroa mites, eliminating a large portion of the Varroa population with limited chemical treatments while retaining the benefits of maintaining adult drones in the population.

Holly A. Wantuch

Papers

Transgenic sexing system for genetic control of the Australian sheep blow fly Lucilia cuprina.

Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor.

Removal of Drone Brood From Apis mellifera (Hymenoptera: Apidae) Colonies to Control Varroa destructor (Acari: Varroidae) and Retain Adult Drones