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The growth in numbers and severity of hospital acquired infections has increased the need to target bacteria locally and specifically. Consequently, smart drug-delivery systems are being developed for local bactericidal action. The approach takes the concept of nanogels in drug delivery of small molecules to the next level by enclosing them in a shell. Versatile polysaccharide nanogels were loaded with zinc ions as antibacterial agents in a miniemulsion process, in order to target methicillin resistant strains of Staphylococcus aureus (MRSA). The encapsulation of drugs in nanogels is limited by the crosslinking density of the gel and the size of the drug. The characterization of the nanogels with inductively coupled plasma optical emission spectroscopy (ICP-OES) revealed that zinc ions cannot be retained within without an additional 'shell' layer. The nanogels were surrounded by a dextran-polyurethane shell, which can retain substances by reduction of water penetration. A delayed zinc release compared to the nanogels was confirmed by ICP-OES. Bacterial tests revealed an antibacterial effect of the shell enhanced nanogels against S. aureus. The studied nanogel system shows potential in locally addressing bacterial infections. The platform is extremely versatile and can be tailored to application as dextran and Zn(NO[sub 3])[sub 2] can be replaced by other polysaccharides (e.g. hyaluronic acid) and antibacterial agents, respectively. [ABSTRACT FROM AUTHOR]

This paper presents the results of a study of the interaction of lipid vesicles with an electroactive, ferrocene alkylthiol self-assembled monolayer (SAM) in terms of the optical changes of the adsorbed lipid layer (measured by surface plasmon resonance (SPR)) and changes in the electrochemical properties of the SAM, as measured by cyclic voltammetry. An curious change in the cyclic voltammogram following adsorption of lipid is observed. We speculate on a possible explanation for this effect. [Copyright &y& Elsevier]

This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine. [ABSTRACT FROM AUTHOR]

Introduction: Systematic reviews (SR) of high-quality randomised controlled trials can identify effective treatments for burn wound infections (BWIs). Clinical heterogeneity in outcome definitions can prevent valid evidence synthesis, which may limit the reliability of the findings of SRs affected by this heterogeneity. This SR aimed to investigate whether there is variation BWI definitions across studies in SRs of burn care interventions and its impact on identification of effective treatments for patients with burn injuries.Methods: A systematic search of five databases was conducted. Included SRs were: in English, published from January 2010 to October 2018, assessed intervention effects for patients with a burn injury, and reported data about BWI.Results: Twenty-nine SRs, which included 248 studies reporting BWI outcomes, were included in our final dataset. Three SRs used a definition of BWI to select studies for inclusion. Fourteen reported BWI definitions from included studies in the review results. There was heterogeneity of BWI definition in their included studies; across 29 SRs, 32 different BWI indicators were used, with the median across SRs ranging from 1 to 7 (range 1-14). Fourteen SRs accounted for BWI definition heterogeneity in their conclusions, indicating that the issue impacted whether a conclusion could be drawn, and limited the validity of the SR findings.Conclusions: There is variation in BWI definition across SRs and within the studies included in SRs of interventions assessing BWI outcomes. This heterogeneity has prevented conclusions about intervention effects being drawn, and only half of the SR authors have accounted for it in their findings. Reviews that have collated this data without reference to the heterogeneity should be viewed with caution, since it may limit the validity of evidence for the identification of effective treatments for BWI. The use of a newly developed core indicator set to support consistent reporting of indicators and standardisation of BWI outcome reporting will enable effective evidence synthesis. [ABSTRACT FROM AUTHOR]

This paper describes the synthesis and application of a novel ferrocene (Fc) label that can be efficiently attached to oligonucleotides. We demonstrate how pulse electrochemical methods can be used to measure very low concentrations of ferrocene label and, importantly, show good electroanalytical discrimination between a labelled oligonucleotide and an enzyme digested labelled oligonucleotide, in which the ferrocene label nucleotide conjugate has been released. Real time in situ analysis gives a much greater understanding of the process. Potential applications include the detection of specific nucleic acid sequences and measurement of nuclease activity. [Copyright &y& Elsevier]

The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV-radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test, respectively. Mutant colonies obtained from the latter were quantitated and sequenced. CAP was found to elicit a similar mutation spectrum to X-irradiation, which did not resemble that for UV implying that CAP-produced RONS are more likely the mutagenic component of CAP. CAP treatment was also shown to promote resistance to the antibiotic ciprofloxacin. Our data suggest that CAP treatment has mutagenic effects that may have important phenotypic consequences. [ABSTRACT FROM AUTHOR]

Antibiotics are commonly used as the first line of defense in the treatment of infectious diseases. However, the rise of antimicrobial resistance (AMR) is rendering many antibiotics less effective. Consequently, effective non-antibiotic antimicrobial strategies are urgently needed to combat AMR. This paper presents a strategy utilizing cold plasma for the "on-demand" activation of acetyl donor molecules. The process generates an aqueous-based antimicrobial formulation comprising a rich mixture of highly oxidizing molecules: peracetic acid, hydrogen peroxide, and other reactive oxygen and nitrogen species. The synergistic potent oxidative action between these molecules is shown to be highly effective at eradicating common wound pathogenic bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) and at inactivating a virus (SARS-CoV-2). [ABSTRACT FROM AUTHOR]

Carboxylesterases (CEs) are widely distributed in the body and catalyze the hydrolysis of endogenous and exogenous substrates. They play important roles in drug metabolism, and abnormal levels often result in numerous diseases such as cancers. Therefore, it is important to establish a highly selective and sensitive probe for the real-time sensing of CEs activity. Herein, we synthesized a novel fluorescence-electrochemical multichannel probe 1 containing a ferrocene unit, which not only serves as part of the structure of probe 1 but also provides electrochemical signals. The probe exhibited high selectivity to CEs with a "Turn-On" fluorescence response and was applied for imaging in complicated biological samples including Staphylococcus aureus , living cells, and zebrafish. Furthermore, the hydrolysis of the acetoxy group of probe 1 by CEs decreased the electrochemical signal. All these results suggest that probe 1 can act as a multi-modal probe for real-time tracking of the activity CEs in complex biological environments. • A ferrocene-chalcone-based probe for detecting CEs by fluorescence and electrochemical signals was developed. • Probe 1 exhibited rapid response, good optical performance, high selectivity, and high sensitivity in solution. • The crystal structure of probe 1 and product 1a were determined. • Endogenous imaging-based CEs-detection in a range of S. aureus species, C6 cells, and zebrafish was achieved. [ABSTRACT FROM AUTHOR]

Carboxylesterases (CEs) are involved in the biotransformation of numerous drugs, environmental toxicants, and carcinogens containing ester groups. Abnormal CEs levels are associated with various diseases, and as such they are widely studied in cells. CEs are also characteristic biomarkers for assisting in the detection of certain strains of bacteria and are involved in important biological processes. Herein, we used two probes including an indene-chalcone-based fluorescent probe which displays green "turn-on" fluorescence response, and a merocyanine-based ratiometric probe to detect CEs, as well as detect and image S. aureus and their chronic biofilms using an acetate ester as recognition group. • Two fluorescent indene-chalcone (turn on) and merocyanine (ratiometric) probes for carboxylesterases were evaluated for bacterial applications. • The probes exhibit rapid response, good optical performance, high selectivity, and high sensitivity. • The probes facilitate the detection and imaging of carboxylesterases in a range of S. aureus species, and clinical biofilms. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae , (Group B Streptococcus (GBS)), is a common colonizer of the female vagina. In women giving birth it can be transmitted to the baby and cause serious illness and even death to the child. We have developed a biosensor comprising of phospholipids and fatty acids vesicles encapsulating high concentration, self-quenched carboxyfluorescein, which is released by the lysis of the vesicle by virulence factors expressed by GBS, becoming diluted and fluorescent. The microbial specificity of the sensor was tested against a number of GBS strains and other microbes including Candida albicans , Enterococcus faecalis and Staphylococcus epidermidis and a statistically significant response to GBS measured over these other microbes. To test the in vivo efficacy of the biosensor, a pilot study using donated lower vaginal swabs from non-pregnant women was conducted, where 58 female adults were recruited. Participants donated two swabs, one which was used for the vesicle test and one for the 'gold standard', enriched culture media (ECM) test. An overall GBS carriage rate of 17.2% was measured using the ECM test. The vesicle biosensor test took 45 min to obtain a result, and showed a sensitivity of 83.3%, specificity of 85.7% and accuracy of 85.3%. The test accuracy is in line with current novel GBS identification tests, with the advantage of being rapid, easy to use, low-cost and able to be conducted by bedside during start of labour. [Display omitted] • Group B Streptococcus (GBS) cause the majority of neonatal infections globally. • Current detection methods are time consuming and cannot be done at bedside. • Phospholipid vesicles encapsulating a self-quenched dye can detect GBS virulence factors. • Phospholipid vesicles detect GBS colonisation in <1 hour and could be used at bedside. [ABSTRACT FROM AUTHOR]

We explore how to configure an argon atmospheric-pressure plasma jet for enhancing its production of hydrogen peroxide (H2O2) in deionised water (DIW). The plasma jet consists of a quartz tube of 1.5 mm inner diameter and 3 mm outer diameter, with an upstream internal needle electrode (within the tube) and a downstream external cylindrical electrode (surrounding the tube). The plasma is operated by purging argon through the glass tube and applying a sinusoidal AC voltage to the internal needle electrode at 10 kV (peak–peak) with a frequency of 23.5 kHz. We study how the following operational parameters influence the production rate of H2O2 in water: tube length, inter-electrode separation distance, distance of the ground electrode from the tube orifice, distance between tube orifice and the DIW, argon flow rate and treatment time. By examining the electrical and optical properties of the plasma jet, we determine how the above operational parameters influence the major plasma processes that promote H2O2 generation through electron-induced dissociation reactions and UV photolysis within the plasma core and in the plasma afterglow; but with a caveat being that these processes are highly dependent on the water vapour content from the argon gas supply and ambient environment. We then demonstrate how the synergistic action between H2O2 and other plasma generated molecules at a plasma induced low pH in the DIW is highly effective at decontaminating common wound pathogens Gram-positive Staphylococus aureus and Gram-negative Pseudomonas aeruginosa. The information presented in this study is relevant in the design of medical plasma devices where production of plasma reactive species such as H2O2 at physiologically useful concentrations is needed to help realise the full clinical potential of the technology. [ABSTRACT FROM AUTHOR]

Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA's competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms. [ABSTRACT FROM AUTHOR]

Two ‘turn on’ TCF-based fluorescence probes were developed for the detection of biological thiols (TCF-GSH and TCFCl-GSH). TCF-GSH was shown to have a high sensitivity towards glutathione (GSH) with a 0.28 μM limit of detection. Unfortunately, at higher GSH concentrations the fluorescence intensity of TCF-GSH decreased and toxicity was observed for TCF-GSH in live cells. However, TCFCl-GSH was shown to be able to detect GSH at biologically relevant concentrations with a 0.45 μM limit of detection. No toxicity was found for TCFCl-GSH and a clear ‘turn on’ with good photostability was observed for the exogenous addition of GSH, Cys and HCys. Furthermore, TCFCl-GSH was used to evaluate the effects of drug treatment on the levels of GSH in live cells. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus infections of the skin and soft tissue pose a major concern to public health, largely owing to the steadily increasing prevalence of drug resistant isolates. As an alternative mode of treatment both bacteriophage endolysins and bacteriocins have been shown to possess antimicrobial efficacy against multiple species of bacteria including otherwise drug resistant strains. Despite this, the administration and exposure of such antimicrobials should be restricted until required in order to discourage the continued evolution of bacterial resistance, whilst maintaining the activity and stability of such proteinaceous structures. Utilising the increase in skin temperature during infection, the truncated bacteriophage endolysin CHAP K and the staphylococcal bacteriocin lysostaphin have been co-administered in a thermally triggered manner from Poly( N -isopropylacrylamide) (PNIPAM) nanoparticles. The thermoresponsive nature of the PNIPAM polymer has been employed in order to achieve the controlled expulsion of a synergistic enzybiotic cocktail consisting of CHAP K and lysostaphin. The point at which this occurs is modifiable, in this case corresponding to the threshold temperature associated with an infected wound. Consequently, bacterial lysis was observed at 37 °C, whilst growth was maintained at the uninfected skin temperature of 32 °C. [ABSTRACT FROM AUTHOR]