A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients

Abstract: Background: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. Methods: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. Discussion: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. Trial registration: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. Trial registration number: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered

Nitrogen and phosphorus co-limitation and grazing moderate nitrogen impacts on plant growth and nutrient cycling in sand dune grassland

Atmospheric nitrogen (N) deposition alters plant biodiversity and ecosystem function in grasslands worldwide. This study examines the impact of 6 years of nutrient addition and grazing management on a sand dune grassland. Results indicate that co-limitation of N and phosphorus (P) moderates the impact of realistic rates of N addition (7.5, 15 kg N ha−1 year−1). Combined NP addition (15 kg N + 10 kg P ha−1 year−1) was the only nutrient treatment to differ significantly from the control, with greater above-ground biomass (mainly moss), and enhanced N and P mineralisation rates. Grazing management altered plant functional group composition, reduced above-ground biomass and meso-faunal feeding rates, and decoupled N and P mineralisation. There were no synergistic effects of grazing and N treatment. Although NP co-limitation apparently prevents adverse impacts of N deposition above the critical load, excess N is likely to be stored in moss biomass and soil, with unknown future consequences

On the antibacterial effects of manuka honey: mechanistic insights

Abstract: Antimicrobial resistance (AMR) is an increasing clinical problem precipitated by the inappropriate use of antibiotics in the later parts of the 20th Century. This problem, coupled with the lack of novel therapeutics in the development pipeline, means AMR is reaching crisis point, with an expected annual death rate of ten million people worldwide by 2050. To reduce, and to potentially remedy this problem, many researchers are looking into natural compounds with antimicrobial and/or antivirulence activity. Manuka honey is an ancient antimicrobial remedy with a good track record against a wide range of nosocomial pathogens that have increased AMR. Its inhibitory effects are the result of its constituent components, which add varying degrees of antimicrobial efficacy to the overall activity of manuka honey. The antimicrobial efficacy of manuka honey and some of its constituent components (such as methylglyoxal and leptosperin) are known to bestow some degree of antimicrobial efficacy to manuka honey. Despite growing in vitro evidence of its antimicrobial efficacy, the in vivo use of manuka honey (especially in a clinical environment) has been unexpectedly slow, partly due to the lack of mechanistic data. The mechanism by which manuka honey achieves its inhibitory efficacy has recently been identified against Staphylococcus aureus and Pseudomonas aeruginosa, with both of these contrasting organisms being inhibited through different mechanisms. Manuka honey inhibits S. aureus by interfering with the cell division process, whereas P. aeruginosa cells lyse in its presence due to the reduction of a key structural protein. In addition to these inhibitory effects, manuka honey is known to reduce virulence, motility, and biofilm formation. With this increasing in vitro dataset, we review the components and our mechanistic knowledge of manuka honey and how manuka honey could potentially be utilized in the future to impact positively on the treatment of microbial, resistant infections. Keywords: Staphylococcus aureus, Pseudomonas aeruginosa, biofilm, antibiotic resistanc

Hierarchical porous nitrogen-rich carbon monoliths via ice-templating: high capacity and high-rate performance as lithium-ion battery anode materials

Hierarchical porous nitrogen-rich carbon monoliths were prepared from a polyacrylonitrile (PAN) precursor by employing a novel & facile ice-templating, thermal annealing and pyrolysis technique. The achieved carbon monoliths were characterised by scanning electron microscopy (SEM), Hg-intrusion porosimetry, thermogravimetric analysis (TGA), N2 gas-sorption, elemental analysis, X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD) and Raman spectroscopy. Electrochemical evaluation of the carbon materials as anodes for the rechargeable lithium-ion battery revealed an impressive stable reversible capacity as high as 745 mA h g−1 at a current density of 50 mA g−1. Incorporation of melamine (for further N-doping) and graphene into the carbon monoliths was achieved easily, and found to significantly enhance high rate performance – with a reversible capacity of about 300 mA h g−1 obtained at the ultra high current density of 10 A g−1

Contrasting effects of linezolid on healthy and dysfunctional human neutrophils: reducing C5a-induced injury

Background: To manage increasing demand for emergency and unscheduled care NHS England policy haspromoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems aredirected to general practitioners (GPs) and other primary care clinicians working within or alongside emergencydepartments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aimof this study was to describe ED clinical leads’ experiences of implementing and delivering ‘primary care services’and ‘emergency medicine services’ where GPs were integrated into the ED team. Methods: We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We usedframework analysis to analyse interview transcripts and explore differences across ‘primary care services’, ‘emergency medicine services’ and emergency departments without primary care services. Results: In EDs with separate primary care services, success was reported when having a distinct workforce ofprimary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way,using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challengeswere: trying to align their service with the policy guidance, inconsistent demand for primary care, accessiblecommunity primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governanceprotocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce successwas reported as managing the demand for both emergency and primary care and reducing admission

A review of selected bee products as potential anti-bacterial, anti-fungal, and anti-viral agents

Antimicrobial resistance (AMR) is one of the greatest medical challenges the world faces. It was estimated recently that by 2050, AMR will account for 10 million extra deaths annually with additional economic costs in the region of $100 trillion. In order to combat this, novel antimicrobial agents with a broad spectrum of activity are required. Bee products, including; honey, propolis, defensins, royal jelly, bee pollen and venom have been used to treat infectious diseases for several centuries, although they were largely disregarded by Western medicine during the antibiotic era. There has since been a resurgence in interest in their antimicrobial properties, especially due to their reported activity against multi-drug resistant pathogens displaying high levels of AMR. In this paper we review the current scientific literature of honey, propolis, honey bee, defensins, royal jelly, bee pollen and bee venom. We highlight the antimicrobial activity each of these products has displayed and potential future research directions

Directed self-assembly of block copolymers for use in bit patterned media fabrication

Reduction of the bit size in conventional magnetic recording media is becoming increasingly difficult due to the superparamagnetic limit. Bit patterned media (BPM) has been proposed as a replacement technology as it will enable hard disk areal densities to increase past 1 Tb in−2. Block copolymer directed self-assembly (BCP DSA) is the leading candidate for forming BPM due to its ability to create uniform patterns over macroscopic areas. Here we review the latest research into two different BCP DSA techniques: graphoepitaxy and chemoepitaxy (or chemical prepatterning). In addition to assessing their potential for forming high density bit patterns, we also review current approaches using these techniques for forming servo patterns, which are required for hard disk drive (HDD) operation. Finally, we review the current state of UV nanoimprint lithography, which is the favoured technique for enabling mass production of BPM HDDs

A 1,000-year-old antimicrobial remedy with anti-Staphylococcal activity

Plant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval so- cieties used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and hu- manities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th Century Anglo-Saxon Leechbook. The remedy repeatedly killed established S. aure- us biofilms in an in vitro model of soft tissue infection and killed methicillin-resistance S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of pre-modern doctors and the poten- tial of ancient texts as a source of new antimicrobial agents

Acute kidney injury: electronic alerts in primary care - findings from a large population cohort

Background: Electronic reporting of AKI has been used to aid early AKI recognition although its relevance to CA-AKI and primary care has not been described. Aims: We described the characteristics and clinical outcomes of patients with CA-AKI, and AKI identified in primary care (PC-AKI) through AKI e-Alerts. Design: A prospective national cohort study was undertaken to collect data on all e-alerts representing adult CA-AKI. Method: The study utilised the biochemistry based AKI electronic (e)-alert system that is established across the Welsh National Health Service. Results: 28.8% of the 22,723 CA-AKI e-alerts were classified as PC-AKI. Ninety-day mortality was 24.0% and lower for PC-AKI vs. non-primary care (non-PC) CA-AKI. Hospitalisation was 22.3% for PC-AKI and associated with greater disease severity, higher mortality, but better renal outcomes (non-recovery: 18.1% vs. 21.6%; progression of pre-existing CKD: 40.5% vs. 58.3%). 49.1% of PC-AKI had a repeat test within seven days, 42.5% between seven and ninety days, and 8.4% was not repeated within ninety days. There was significantly more non-recovery (24.0% vs. 17.9%) and progression of pre-existing CKD (63.3% vs. 47.0%) in patients with late repeated measurement of renal function compared to those with early repeated measurement of renal function. Conclusion: The data demonstrate the clinical utility of AKI e-alerts in primary care. We recommend that a clinical review, or referral together with a repeat measurement of renal function within seven days should be considered an appropriate response to AKI e-alerts in primary care

Severe hyperkalaemia: demographics and outcome

Background. Few studies have evaluated the prevalence of severe hyperkalaemia in unselected patient populations.We identified all episodes of severe hyperkalaemia occurring in 1 year, and described patient demographics, clinical response and outcome. We also assessed junior doctor knowledge of its causes and significance. Materials and methods. A retrospective interrogation of the database of the regional biochemical laboratory identified all episodes of severe hyperkalaemia (K ≥ 6.5 mmol/L) occurring in 2011. The understanding of trainee doctors of the importance, causes and treatment of severe hyperkalaemia was assessed by structured questionnaire. Results. Severe hyperkalaemia was recorded in 433 samples (365 patients) giving a prevalence of 0.11%. Thirty-six per cent of episodes occurred in patients under the care of a nephrologist, who were significantly younger than those not under the care of a nephrologist. In the nephrology cohort, 86% occurred in patients with chronic kidney disease (CKD), the majority of which had CKD Stage 5. In the non-nephrology cohort, only 65% occurred in the context of CKD, which was equally distributed between Stages 3 and 5 CKD. In both patient groups, roughly 50% of episodes occurred in association with acute kidney injury (AKI). Acute mortality (death within 48 h of documented severe hyperkalaemia) was higher in the non-nephrology compared with the nephrology cohort. Time to repeat serum potassium was influenced by the clinical setting with shorter time to repeat for acute care compared with ward settings. Assessment of trainee doctor’s knowledge suggested significant deficiencies in relation to severe hyperkalaemia. Conclusions. The prevalence of severe hyperkalaemia was low and occurred predominantly in the context of CKD and/or AKI. The majority of episodes occurred in patients not under the care of a nephrologist. Variability in time to repeat serum potassium levels suggested deficiencies in care, and assessment of trainee doctor’s knowledge suggests the need for further educational initiatives to highlight its importance