A review of the potential for bacteriophages to effect antibiofilm activity, using selected examples.

It has been over a hundred years since the original publications on bacteriophages were first presented. In the following century, the world of microbiology has moved on significantly. In 2015, ∼100 years later, the UK Government and the Wellcome Trust published a report on the current state of antimicrobial resistance, with guidance for the future. The pressing need for new antibiotics, or alternatives to them, is one of the fundamental drivers of research in to the application of bacteriophages to treat incidents of infectious disease. This review will look at research published on the use of bacteriophages, with a specific focus on their use against bacterial biofilms.

Individualized prescribing portraits to reduce inappropriate initiation of opioid analgesics to opioid naïve patients in primary care: Protocol for a randomized controlled trial.

Background Opioid analgesics are frequently initiated for chronic and acute pain despite weak evidence of benefit, although prescribing rates of some analgesics decreased in the context of the epidemic. In some populations, up to a quarter of opioid naïve persons prescribed opioids for non-cancer pain develop prescription opioid use disorder (OUD). Audit and feedback interventions rely on constructive use of routinely collected data to align professional behaviours and clinical practice with best evidence. These interventions have been shown to help reduce inappropriate initiation. However, effectiveness and acceptability of individualized "portraits" of physicians' prescribing patterns, to reduce inappropriate initiation of opioid analgesics to opioid naïve persons, have not been evaluated. Methods REDONNA is a mixed-methods randomized study testing the effectiveness of individualized prescribing Portraits to reduce inappropriate initiation of opioid analgesics. This intervention to improve safety of opioid prescribing in primary care in British Columbia (BC), Canada involves mailing individual prescribing portraits to an 'early group' of 2604 family physicians, followed in 6 months by a mailing to 2553 family physicians in the 'delayed group'. Primary outcome is number of new opioid prescriptions initiated in opioid naïve people, measured using administrative data from a centralized medication monitoring database covering all prescription opioids dispensed from BC community pharmacies. Secondary endpoints will compare prescribing impact between the two groups. A qualitative sub-study will examine feasibility among a purposive sample of physicians and patients. Discussion This trial provides important evidence on the intervention's potential to steer policy and practice on inappropriate opioid analgesics initiation. Trial registration: The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811).

Corticosteroid signaling at the brain-immune interface impedes coping with severe psychological stress.

The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of Gata3- and Foxp3-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress.

Offensive waste valorisation in the UK: Assessment of the potentials for absorbent hygiene product (AHP) recycling.

Offensive human waste refers to non-hazardous waste that contains body fluids from non-infectious humans, comprised of post-consumer Absorbent Hygiene Products (AHPs), swabs, dressings, bedding, gloves, and other materials. While this waste category requires more stringent handling, storage and disposal measures than general waste, its non-hazardous nature suggests that there are opportunities for waste valorisation. An inventory of 200 offensive human waste bags collected from various healthcare institutions in South-Eastern England show that about 76% of the waste is comprised of AHPs, most of which are adult incontinence pads and child nappies. Mixed plastics comprised of predominantly HDPE represent 9% of the waste. To evaluate the potentials for offensive human waste valorisation, small-scale separation tests involving artificially-soiled nappies and associated mixed plastic packaging wastes have been performed. Findings suggest that about 50% of the total superabsorbent polymer is recoverable from fluff pulp fractions, recoveries of which are unaffected by the presence of ionic species typically present in human waste. On the other hand, recovery of mixed plastic packaging is more challenging. Overall, however, findings suggest that viable AHP recycling is possible if recyclate materials are targeted towards non-food related markets outlets such as the construction and land remediation sectors.

Antibiofilm potential of purified environmental bacteriophage preparations against early stage Pseudomonas aeruginosa biofilms.

AIMS: This paper presents the potential of environmentally sourced bacteriophages to affect the growth of clinical isolates of Pseudomonas aeruginosa biofilms, and assesses the respective plaque morphotypes presented by each bacteriophage, in vitro. METHODS AND RESULTS: Bacterial host strains were typed for their ability to produce the quorum sensing-controlled virulence factor pyocyanin, and then tested for bacteriophage susceptibility using the spot test method. The bacteriophages were co-administered with ciprofloxacin in order to determine whether the bacteriophages would demonstrate synergistic or antagonistic behaviour to the antibiotic in vitro. Results suggest a potential relationship between the bacteriophage plaque size and biofilm inhibition, where those producing smaller plaques appear to be more effective at reducing bacterial biofilm formation. CONCLUSIONS: This phenomenon may be explained by a high adsorption rate leading to the rapid formation of smaller plaques, and greater biofilm reduction associated with the loss of viable bacterial cells before the cells can adhere to the surface and form a biofilm. Results from the co-administration of bacteriophage and ciprofloxacin suggest that the two work synergistically to affect P. aeruginosa biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The data indicate enhanced efficacy of ciprofloxacin by ≥50%. This could offer an alternative strategy for targeting antibiotic-resistant infections.

The effect of urinary Foley catheter substrate material on the antimicrobial potential of calixerene-based molecules.

AIMS: This study was to investigate the antimicrobial activity of a modified calixarene polymer bound to a silicone substrate in the presence of pathogens associated with catheter infections, Escherichia coli and Proteus mirabilis. METHODS AND RESULTS: The molecule and its constituent parts were studied bound and unbound to silicone substrates to ascertain growth effects. Minimum inhibitory and bactericidal concentrations were determined against E. coli and P. mirabilis. Biofilm growth was studied by immersing silicone discs seeded with either P. mirabilis or E. coli in artificial urine. Biofilms were assessed at 3, 7 and 10 days. The coated material reduced bacterial cell density compared to the uncoated samples. Direct and indirect toxicity tests were conducted with a fibroblast cell line (3T3); coated and noncoated silicone samples were seeded with cells (1 × 104 /cm2 ) and incubated for 72 h. Hoechst propidium iodide staining identified delayed toxic effect from the coated and noncoated material leachate in all but the platinum-cured medical-grade silicone, which showed no evident toxicity. CONCLUSIONS: The calixerene polymer was determined to be the active part of the coating. Biofilm formation was dramatically reduced in the coated platinum-cured medical-grade silicone samples, but cell viability was reduced on the clinical-grade silicones regardless of coating in contrast to cells seeded on the platinum-cured medical-grade silicone. A delayed toxic response was evident to the extract of the coated and noncoated clinical-grade samples, indicating that the toxic effect is due to the underlying substrate. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has established that the immobilized molecule enhances the antibacterial and antifouling properties of silicone, without toxicity. It also clearly demonstrates that regardless of coating efficacy, the substrate material has the capacity to disrupt its potency and change the nature of the material coating.

Annexin A2, autoimmunity, anxiety and depression.

OBJECTIVES: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model. METHODS: Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11. RESULTS: Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% ± 0.89% of the time in the center compared to 8.64% ± 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes. CONCLUSIONS: We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain.

A role for ecology in the evolution of colour variation and sexual dimorphism in Hawaiian damselflies.

Variation in traits that are sexually dimorphic is usually attributed to sexual selection, in part because the influence of ecological differences between sexes can be difficult to identify. Sex-limited dimorphisms, however, provide an opportunity to test ecological selection disentangled from reproductive differences between the sexes. Here, we test the hypothesis that ecological differences play a role in the evolution of body colour variation within and between sexes in a radiation of endemic Hawaiian damselflies. We analysed 17 Megalagrion damselflies species in a phylogenetic linear regression, including three newly discovered cases of species with female-limited dimorphism. We find that rapid colour evolution during the radiation has resulted in no phylogenetic signal for most colour and habitat traits. However, a single ecological variable, exposure to solar radiation (as measured by canopy cover) significantly predicts body colour variation within sexes (female-limited dimorphism), between sexes (sexual dimorphism), and among populations and species. Surprisingly, the degree of sexual dimorphism in body colour is also positively correlated with the degree of habitat differences between sexes. Specifically, redder colouration is associated with more exposure to solar radiation, both within and between species. We discuss potential functions of the pigmentation, including antioxidant properties that would explain the association with light (specifically UV) exposure, and consider alternative mechanisms that may drive these patterns of sexual dimorphism and colour variation.