Glucagon-like peptide-1 treatment reduces the risk of diabetes-type 2 related amputations:A cohort study in Denmark

Aims: To assess the impact of Glucagon-like peptide-1 (GLP-1) agonists on the risk of lower extremity amputations in patients with type 2 diabetes mellitus (DM2). Methods: We conducted a cohort study on 309,116 patients with DM2 using Danish National Register and Diabetes Database. We tracked the GLP-1 agonists over time along with the medication dose. Time-varying models are used to assess the risk of amputation for patients with/without GLP-1 treatment. Results: Patients on GLP-1 treatment experience a notable reduction in the risk of amputation compared to those without the treatment with a hazard ratio (HR) of 0.5, 95% CI [0.54–0.74], indicating a statistically significant difference (p &lt;.005). This risk reduction was consistent across different age groups, but notably most pronounced among middle income patients. The findings were further validated by using time-varying Cox models, which considered the patient's comorbidity history. Conclusions: Our analysis reveals compelling evidence of a reduced risk of amputation among patients receiving GLP-1 therapy, an effect dominated by liraglutide, compared to those without the treatment, even after adjusting for various socio-economic factors. However, further investigation is required to identify and account for any other potential confounding variables that may impact the outcome.</p

Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa

Most multicellular animals belong to two evolutionary lineages, the Proto– and Deuterostomia, which diverged 640–760 million years (MYR) ago. Neuropeptide signaling is abundant in animals belonging to both lineages, but it is often unclear whether there exist evolutionary relationships between the neuropeptide systems used by proto- or deuterostomes. An exception, however, are members of the gonadotropin-releasing hormone (GnRH) receptor superfamily, which occur in both evolutionary lineages, where GnRHs are the ligands in Deuterostomia and GnRH-like peptides, adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP) are the ligands in Protostomia. AKH is a well-studied insect neuropeptide that mobilizes lipids and carbohydrates from the insect fat body during flight. In our present paper, we show that AKH is not only widespread in insects, but also in other Ecdysozoa and in Lophotrochozoa. Furthermore, we have cloned and deorphanized two G protein-coupled receptors (GPCRs) from the oyster Crassostrea gigas (Mollusca) that are activated by low nanomolar concentrations of oyster AKH (pQVSFSTNWGSamide). Our discovery of functional AKH receptors in molluscs is especially significant, because it traces the emergence of AKH signaling back to about 550 MYR ago and brings us closer to a more complete understanding of the evolutionary origins of the GnRH receptor superfamily

A novel chronic wound biofilm model sustaining coexistence of Pseudomonas aeruginosa and Staphylococcus aureus suitable for testing of antibiofilm effect of antimicrobial solutions and wound dressings

Chronic wounds are a large burden to patients and healthcare systems. Biofilm infections in chronic wounds are crucial factors leading to non‐healing of wounds. It is important to study biofilm in wounds and to develop effective interventions against wound biofilm. This study presents a novel in vitro biofilm model mimicking infected chronic wounds. The novel layered chronic wound biofilm model uses woundlike media and includes both Pseudomonas aeruginosa and Staphylococcus aureus, which have been identified as the most important pathogens in wounds. The model sustains their coexistence for at least 96 h. Microscopy of the model revealed microbial growth in non‐surface attached microcolonies as previously observed in vivo. The model was used to determine log(10)‐reduction for the use of an antimicrobial solution and antimicrobial dressings (containing silver or honey) showing moderate‐to‐low antibiofilm effect, which indicates better concordance with the observed clinical performance of this type of treatment than other widely used standard tests