Acquisition of a mucoid phenotype by Pseudomonas sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol−1) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid Pseudomonas aeruginosa (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca2+ and DNA were studied using molecular dynamics (MD) simulations, Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (≥0.5%) inhibited biofilm formation, revealing a significant reduction in both biomass and biofilm height (P < 0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of EPS polysaccharides, and extracellular (e)DNA (P < 0.05) with a corresponding increase in nanoparticle diffusion (P < 0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca2+ evident in FTIR and MD modelling. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca2+-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections.

No abstract

No abstract

In this paper, we present a comprehensive analytical model of Tm able to take into account direct cross-relaxation process. We show that by using an appropriate set of parameters the model is able to properly fit the first part of the fluorescence decay of Tm-doped tellurite glasses for different dopant concentration values. We also compare the model with a full numerical model to investigate its limitations. We assess the model is a valid tool to fit fluorescence properties but for predicting population inversion is limited to doping level up to about 1%. In case of higher doping the reverse cross-relaxation process becomes significant,. .

Background Advance Therapy Medicinal Products (ATMPs) are a novel class of therapeutics that target chronic and severe conditions, which can have an impact beyond the patient themselves; impacting the lives of partners and other family members. This impact is a major secondary burden of disease that in the past has often been ignored. The Family-Reported Outcome Measure (FROM-16) is the first generic questionnaire designed to measure the impact of any disease on the quality of life of family members of patients with any health condition. We seek to validate the FROM-16 as an instrument for assessing family impact of patients receiving ATMPs and demonstrate a potential mechanism for measuring this impact. Methods Up to 30 patients of any age who are preparing for ATMP treatment, or who have received an ATMP treatment, and their family members aged 18 years or older, attending ATMP provider sites within the Midland-Wales Advanced Therapy Treatment Centre will be recruited into this study. Family members will be asked to complete the FROM-16 and Global Health Score questionnaires, provide basic demographic information and complete a short semi-structured interview conducted by a member of the study team. The interview will provide data to contextualise the FROM-16 responses and allow construct and content validity to be assessed. Themes of experience will be identified from interview transcripts. The FROM-16 responses will be evaluated with respect to total score, domain score, and individual item score. Reliability of responses between and within domains will be assessed by intraclass correlation. Discussion Collecting FROM data from families can be important for demonstrating the wider impact of disease. This study, if successful, will demonstrate that collecting family-reported outcomes using the FROM-16 is a valid mechanism for demonstrating this impact within the population of ATMP patients and their families, and will provide evidence of the overall quality of life impact experienced by partners and family members of such patients, and the specific impacts as identified from the two domains and 16 questions within FROM-16. Trial Registration This trial has been adopted onto the NIHR portfolio (I.D. 51376) and registered with https://clinicaltrials.gov/ct2/show/NCT05141318 (#NCT05141318) in December 2021.