Human dermal fibroblast subpopulations and epithelial mesenchymal transition signals in hidradenitis suppurativa tunnels are normalized by spleen tyrosine kinase antagonism in vivo.

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology.

In vitro and in vivo evaluation of the antimicrobial effectiveness of non-medicated hydrophobic wound dressings.

There is an increasing use of non-medicated wound dressing with claims of irreversible bacterial binding. Most of the data are from in vitro models which lack clinical relevance. This study employed a range of in vitro experiments to address this gap and we complemented our experimental designs with in vivo observations using dressings obtained from patients with diabetes-related foot ulcers.

In vivo observations of biofilm adhering to a dialkylcarbamoyl chloride-coated mesh dressing when applied to diabetes-related foot ulcers: A proof of concept study.

In this proof-of-concept study of twenty participants, we sought to determine if a DACC (Dialkylcarbamoyl chloride)-coated mesh dressing demonstrates an ability to adhere biofilm when placed on Diabetes Related Foot Ulcers (DRFUs) with chronic infection. The study also sought to determine if removal of the DACC-coated mesh dressings contributes to reducing the total number of bacteria in DRFUs, by exploring the total microbial loads, microbial community composition, and diversity. Standard of care was provided in addition to the application of DACC or DACC hydrogel every three days for a total of two weeks.

Metatranscriptome sequencing identifies are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis.

Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that spp.

Culture-Free Phylogenetic Analysis of Legionella pneumophila Using Targeted CRISPR/Cas9 Next-Generation Sequencing.

Currently available methods for the laboratory investigation of Legionella pneumophila outbreaks require organism culture. The ability to sequence L. pneumophila directly from clinical samples would significantly reduce delays.

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK-STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species.

Host-microbe metatranscriptome reveals differences between acute and chronic infections in diabetes-related foot ulcers.

Virtually all diabetes-related foot ulcers (DRFUs) will become colonized by microorganisms that may increase the risk of developing an infection. The reasons why some ulcerations develop acute clinical infections (AI-DRFUs) whilst others develop chronic infection (CI-DRFUs) and the preceding host-microbe interactions in vivo remain largely unknown. Establishing that acute and chronic infections are distinct processes requires demonstrating that these are two different strategies employed by microbes when interacting with a host.

Efficacy of a Topical Wound Agent Methanesulfonic Acid and Dimethylsulfoxide on In Vitro Biofilms.

A topical desiccating wound agent containing methanesulfonic acid, dimethylsulfoxide and amorphous silica was evaluated in three in vitro models for its efficacy against biofilms produced by (ATCC-15442) and (ATCC-6538). The in vitro biofilm models used were; the MBEC Assay, Centre for Disease Control (CDC) Biofilm Reactor and a Semi-solid biofilm model. A 30-s exposure of a topical wound desiccating agent was used in each model.

A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study.

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs.

Efficacy of a topical concentrated surfactant gel on microbial communities in non-healing diabetic foot ulcers with chronic biofilm infections: A proof-of-concept study.

This proof-of-concept study sought to determine the effects of standard of care (SOC) and a topically applied concentrated surfactant gel (SG) on the total microbial load, community composition, and community diversity in non-healing diabetic foot ulcers (DFUs) with chronic biofilm infections. SOC was provided in addition to a topical concentrated SG, applied every 2 days for 6 weeks. Wound swabs were obtained from the base of ulcers at baseline (week 0), week 1, mid-point (week 3), and end of treatment (week 6).

Effect on total microbial load and community composition with two vs six-week topical Cadexomer Iodine for treating chronic biofilm infections in diabetic foot ulcers.

This study compares two vs six weeks of topical antimicrobial therapy with Cadexomer Iodine in patients with diabetic foot ulcers (DFUs) complicated by chronic biofilm infections. Patients with non-healing DFUs with suspected chronic biofilm infections were eligible for enrolment. Patients were randomised to receive either two or six weeks of treatment with topical Cadexomer Iodine.

Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture, DNA sequencing and microscopy.

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra-operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six-month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be 'clean/non-infected' were collected.