Optimisation of Additives to Maximise Performance of Expandable Graphite-Based Intumescent-Flame-Retardant Polyurethane Composites.

The effect of varying the weight percentage composition (wt.%) of low-cost expandable graphite (EG), ammonium polyphosphate (APP), fibreglass (FG), and vermiculite (VMT) in polyurethane (PU) polymer was studied using a traditional intumescent flame retardant (IFR) system. The synergistic effect between EG, APP, FG, and VMT on the flame retardant properties of the PU composites was investigated using SEM, TGA, tensile strength tests, and cone calorimetry. The IFR that contained PU composites with 40 wt.% EG displayed superior flame retardant performance compared with the composites containing only 20 w.t.% or 10 w.t.% EG. The peak heat release rate, total smoke release, and carbon dioxide production from the 40 wt.% EG sample along with APP, FG, and VMT in the PU composite were 88%, 93%, and 92% less than the PU control sample, respectively. As a result, the synergistic effect was greatly influenced by the compactness of the united protective layer. The PU composite suppressed smoke emission and inhibited air penetrating the composite, thus reducing reactions with the gas volatiles of the material. SEM images and TGA results provided positive evidence for the combustion tests. Further, the mechanical properties of PU composites were also investigated. As expected, compared with control PU, the addition of flame-retardant additives decreased the tensile strength, but this was ameliorated with the addition of FG. These new PU composite materials provide a promising strategy for producing polymer composites with flame retardation and smoke suppression for construction materials.

Fabrication of a Low-Cost Microfluidic Device for High-Throughput Drug Testing on Static and Dynamic Cancer Spheroid Culture Models.

Drug development is a complex and expensive process from new drug discovery to product approval. Most drug screening and testing rely on in vitro 2D cell culture models; however, they generally lack in vivo tissue microarchitecture and physiological functionality. Therefore, many researchers have used engineering methods, such as microfluidic devices, to culture 3D cells in dynamic conditions. In this study, a simple and low-cost microfluidic device was fabricated using Poly Methyl Methacrylate (PMMA), a widely available material, and the total cost of the completed device was USD 17.75. Dynamic and static cell culture examinations were applied to monitor the growth of 3D cells. α-MG-loaded GA liposomes were used as the drug to test cell viability in 3D cancer spheroids. Two cell culture conditions (i.e., static and dynamic) were also used in drug testing to simulate the effect of flow on drug cytotoxicity. Results from all assays showed that with the velocity of 0.005 mL/min, cell viability was significantly impaired to nearly 30% after 72 h in a dynamic culture. This device is expected to improve in vitro testing models, reduce and eliminate unsuitable compounds, and select more accurate combinations for in vivo testing.

Effect of Cationic Groups on the Selectivity of Ternary Antimicrobial Polymers.

Antimicrobial polymers (AMPs) have emerged as a promising approach to combat multidrug-resistant pathogens. Developed from binary polymers, which contain cationic and hydrophobic groups, ternary polymers are enhanced by adding neutral hydrophilic monomers to improve their biocompatibility. Cationic groups have attracted significant attention owing to their pivotal role in AMPs. Although many studies have investigated the effect of cationic groups on antimicrobial activity of binary AMPs, there is a lack of comprehensive and systematic evaluation for ternary AMPs. Therefore, a library of 31 statistical amphiphilic ternary polymers containing different cationic groups, including primary amine, guanidine, and sulfonium groups is prepared to investigate the impact of cationic groups on antimicrobial activity and biocompatibility. It is shown that the cationic balance appears to be a critical factor influencing polymers' antibacterial activity and selectivity. The results reveal that the polymers that have the ratio of the cationic groups ranging between 50% and 60%, coupled with a cationic/hydrophobic ratio in the range of [1.4-2] and an appropriate neutral hydrophilic/hydrophobic balance, exhibited the highest selectivity toward mammalian cells. This study elucidates a structure-property-performance relationship for ternary AMPs, which contributes to the development of AMPs capable of selectively targeting gram-negative pathogens.

More than skin deep: using polymers to facilitate topical delivery of nitric oxide.

Skin, the largest organ in the human body, provides several important functions, including providing protection from mechanical impacts, micro-organisms, radiation and chemicals; regulation of body temperature; the sensations of touch and temperature; and the synthesis of several substances including vitamin D, melanin, and keratin. Common dermatological disorders (CDDs) include inflammatory or immune-mediated skin diseases, skin infection, skin cancer, and wounds. In the treatment of skin disorders, topical administration has advantages over other routes of administration, and polymers are widely used as vehicles to facilitate the delivery of topical therapeutic agents, serving as matrices to keep therapeutic agents in contact with the skin. Nitric oxide (NO), a cellular signalling molecule, has attracted significant interest in treating a broad spectrum of diseases, including various skin disorders. However, there are a number of challenges in effectively delivering NO. It must be delivered in a controlled manner at sufficient concentrations to be efficacious and the delivery system must be stable during storage. The use of polymer-based systems to deliver NO topically can be an effective strategy to overcome these challenges. There are three main approaches for incorporating NO with polymers in topical delivery systems: (i) physical incorporation of NO donors into polymer bases; (ii) covalent attachment of NO donors to polymers; and (iii) encapsulation of NO donors in polymer-based particles. The latter two approaches provide the greatest control over NO release and have been used by numerous researchers in treating CDDs, including chronic wounds and skin cancer.

How we diagnose 2M von Willebrand disease (VWD): Use of a strategic algorithmic approach to distinguish 2M VWD from other VWD types.

INTRODUCTION: von Willebrand disease (VWD) is the most common inherited bleeding disorder and caused by an absence, deficiency or defect in von Willebrand factor (VWF). VWD is currently classified into six different types: 1, 2A, 2B, 2N, 2M, 3. Notably, 2M VWD is more often misdiagnosed as 2A or type 1 VWD than properly identified as 2M VWD. AIM: To describe an algorithmic approach to better ensure appropriate identification of 2M VWD, and reduce its misdiagnosis, as supported by sequential laboratory testing. METHODS: Comparative assessment of types 1, 2A, 2B and 2M VWD using various laboratory tests, including VWF antigen and several VWF activity assays, plus DDAVP challenge data, ristocetin-induced platelet agglutination (RIPA) data, multimer analysis and genetic testing. RESULTS: Types 1, 2A, 2B and 2M VWD give characteristic test patterns that can provisionally classify patients into particular VWD types. Notably, type 1 VWD shows low levels of VWF, but VWF functional concordance (VWF activity/Ag ratios >0.6), with both baseline assessment and post-DDAVP. Types 2A, 2B and 2M VWD show VWF functional discordance (low VWF activity/Ag ratio(s)) dependent on the defect, but type 2M separates from 2A/2B VWD based on specific test patterns, especially with collagen binding vs glycoprotein Ib binding assays. RIPA identifies 2B VWD. Multimers separate 2M from 2A/2B. CONCLUSION: We provide strategies to improve correct diagnosis of VWD, especially focussed on 2M VWD, and which can be used by most diagnostic haemostasis laboratories, reserving genetic analysis (if required) for confirmation.

Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers.

Antimicrobial polymers have emerged as a potential solution to the growing problem of antimicrobial resistance. Although several studies have examined the effects of various parameters on the antimicrobial and hemolytic activity of statistical copolymers, there are still numerous parameters to be explored. Therefore, in this study, we developed a library of 36 statistical amphiphilic ternary copolymers prepared via photoinduced electron transfer-reversible addition-fragmentation chain transfer polymerization to systematically evaluate the influence of hydrophobic groups [number of carbons (5, 7, and 9)] and chain type of the hydrophobic monomer (cyclic, aromatic, linear, or branched), monomer ratio, and degree of polymerization (DPn) on antimicrobial and hemolytic activity. To guide our synthetic strategy, we developed a pre-experimental screening approach using C log P values of oligomer models, which correspond to the logarithm of the partition coefficient of compounds between n-octanol and water. This method enabled correlation of polymer hydrophobicity with antimicrobial and hemolytic activity. In addition, this study revealed that minimizing hydrophobicity and hydrophobic content were key factors in controlling hemolysis, whereas optimizing antimicrobial activity was more complex. High antimicrobial activity required hydrophobicity (i.e., C log P, hydrophobicity index) that was neither too high nor too low, an appropriate cationic/hydrophobic balance, and structural compatibility between the chosen monomers. Furthermore, these findings could guide the design of future antimicrobial ternary copolymers and suggest that C log P values between 0 and 2 have the best balance of high antimicrobial activity and low hemolytic activity.

Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies.

INTRODUCTION: Diagnosis of von Willebrand disease (VWD) is challenging due to heterogeneity of VWD and test limitations. Many von Willebrand factor (VWF) assays are utilized, including antigen (Ag), activity and multimer analysis. Activity assays include ristocetin cofactor using platelets (VWF:RCo) or other particles incorporating recombinant glycoprotein I ('VWF:GPIbR'), or other GPI binding assays using gain-of-function mutations ('VWF:GPIbM'), or collagen binding (VWF:CB). AIM: To comparatively evaluate modern contemporary VWF activity assays vs VWF multimer analysis using modern contemporary methods. MATERIALS AND METHODS: Several VWF activity assays (VWF:RCo, VWF:GPIbR, VWF:GPIbM, VWF:CB) assessed (typically as a ratio against VWF:Ag) against a new semi-automated procedure for different types of VWD (1, 3, 2A, 2B, 2M), plus control material (n = 580). The evaluation also focussed on relative loss of high and very high molecular weight multimers (HMWM and VHMWM) by densitometric scanning. RESULTS: All evaluated VWF activity/Ag ratios showed high correlation to the presence/absence of HMWM and VHMWM, although VWF:CB/Ag and VWF:GPIbR/Ag ratios using an automated chemiluminescence method yielded highest correlation coefficients (r = .909 and .874, respectively, for HMWM). Use of the investigative procedure (VHMWM) identified fewer false positives for 'loss' in type 1 VWD. CONCLUSIONS: This comparative investigation identified that new automated chemiluminescence VWF activity assays best identified relative loss or presence of HMWM and VHMWM according to activity to Ag ratios and an alternative investigative method for identifying VHMWM in multimer testing for a new commercial multimer method may lead to fewer false identifications of HMW loss in type 1 VWD.

The KidzMed project: teaching children to swallow tablet medication.

Tablets are safer, more convenient and cheaper than liquid medications. Children and young people (CYP) often remain on liquids due to habit, reluctance to change or staff and parents' lack of knowledge about switching to tablets. We describe a quality improvement project to train staff and embed a system of converting eligible children to tablet medication. A series of tests of change were made including training, making kit available, publicity and developing team protocols. In 3 months, 21 out of 25 eligible CYP were successfully converted with added benefit of saving £46 588 per year. Switching children to tablets is simple but requires whole team engagement, culture change of expectations and available resources.

Semi-automated von Willebrand factor multimer assay for von Willebrand disease: Further validation, benefits and limitations.

INTRODUCTION: Accurate diagnosis of von Willebrand disease (VWD) enables effective patient management. von Willebrand factor (VWF) multimer analysis provides useful information regarding VWF multimer structure, thereby aiding VWD subtyping and management; however, historically technically challenging assays have had limited utility. This study evaluates the Sebia Hydrasys Hydragel-11 semi-automated VWF multimer assay and further validates the Hydragel-5 gel system, as primarily pertaining to VWD diagnostics and monitoring of therapy. METHODS: Provisionally diagnosed (via a reference assay test panel) archived patient samples and prospective test patient samples, including those undergoing desmopressin trial or therapy monitoring, along with commercial and in-house control material and various external quality assessment (EQA) samples, were analysed. VWF multimers were evaluated for presence, loss or partial loss of high molecular weight (HMWM) and intermediate molecular weight (IMWM) multimers by both visual inspection and densitometric scanning, and comparison with reference assay results. RESULTS: All anticipated multimer patterns were reproduced, with patients generally showing multimer profiles matching expected patterns according to VWD type based on reference test panel 'diagnosis'. Occasional discrepancies were resolved by retesting. The increase in plasma VWF following desmopressin therapy was also clearly demonstrated. Multimer profiles of EQA samples complemented reference test panel results and matched EQA targets. There were some 'technical' limitations noted. CONCLUSION: This easy to use, standardised, semi-automated multimer analysis system can demonstrate the multimer profile of VWD patients, thus representing an additional laboratory tool for improved diagnosis, thereby facilitating appropriate patient management.

Tuning crystallization and morphology of zinc oxide with polyvinylpyrrolidone: Formation mechanisms and antimicrobial activity.

Zinc oxide (ZnO) particles with different shapes and sizes have been previously reported to possess unique optical, electrical, photocatalytic, and antimicrobial properties. Capping agents are routinely used to control particle morphologies; however, few studies have evaluated the influence of capping agents on the growth kinetics of ZnO particles of different shapes. Herein, we report a simple water-based chemical precipitation method to produce unique bowtie-, flower-, and nest-shaped ZnO particles using zinc nitrate and urea in the presence of polyvinylpyrrolidone (PVP). Three distinct particle morphologies are obtained by adjusting polymer concentration during synthesis. This approach is simple and could enable large-scale production of ZnO particles with diverse shapes. We monitor the morphological evolution of ZnO particles and, at different polymer concentrations, uncover the preferable PVP adsorption onto different ZnO facets that controls the growth directions of ZnO. Previous reports have demonstrated the influence of particle shape on ZnO antibacterial activity. In this study, we show that ZnO particles with these three morphologies exhibit similar bacterial killing efficacy towards Escherichia coli and Staphylococcus aureus. Our detailed mechanistic studies suggest that the antibacterial mechanism of ZnO particles can be attributed to both Zn2+ release and oxidative stress, whereas shape plays only a minor role in the antibacterial activity of ZnO particles.

Water Soluble Antioxidant Dextran-Quercetin Conjugate with Potential Anticancer Properties.

Quercetin, a naturally occurring potent antioxidant, is limited in therapeutic use, owing to its poor water solubility and stability. Herein, a method of conjugating quercetin to an aldehyde functionalized dextran via an HCl catalyzed condensation reaction to yield a water soluble quercetin functionalized polymer is reported. The prepared conjugate is characterized by 1 H and 1 H-13 C heteronuclear single quantum correlation (HSQC) NMR, which demonstrate that conjugation occurs via both the A- and B-rings of quercetin. The degree of quercetin functionalization can be tuned by varying the reaction temperature and/or the concentration of the HCl catalyst. However, as temperatures and HCl concentrations are increased above 40 °C and 2 m, respectively, the increase in functionalization is accompanied by an increase in the oxidation of the conjugated quercetin and a decrease in polymer yield. The prepared conjugate is shown to have improved stability compared with native quercetin while maintaining substantial free-radical scavenging activity. Anticancer activity is evaluated in vitro in a neuroblastoma cell line. The dextran-aldehyde-quercetin conjugate prepared at 40 °C and 2 m HCl is shown to be cytotoxic to neuroblastoma cells (SH-SY5Y-IC50 = 123 µg mL-1 and BE(2)-C-IC50 = 380 µg mL-1 ) but shows no activity against nonmalignant MRC-5 cells at concentrations up to 400 µg mL-1 .

2017 EULAR recommendations for a core data set to support observational research and clinical care in rheumatoid arthritis.

Personalised medicine, new discoveries and studies on rare exposures or outcomes require large samples that are increasingly difficult for any single investigator to obtain. Collaborative work is limited by heterogeneities, both what is being collected and how it is defined. To develop a core set for data collection in rheumatoid arthritis (RA) research which (1) allows harmonisation of data collection in future observational studies, (2) acts as a common data model against which existing databases can be mapped and (3) serves as a template for standardised data collection in routine clinical practice to support generation of research-quality data. A multistep, international multistakeholder consensus process was carried out involving voting via online surveys and two face-to-face meetings. A core set of 21 items ('what to collect') and their instruments ('how to collect') was agreed: age, gender, disease duration, diagnosis of RA, body mass index, smoking, swollen/tender joints, patient/evaluator global, pain, quality of life, function, composite scores, acute phase reactants, serology, structural damage, treatment and comorbidities. The core set should facilitate collaborative research, allow for comparisons across studies and harmonise future data from clinical practice via electronic medical record systems.

Enhancing the antimicrobial and antibiofilm effectiveness of silver nanoparticles prepared by green synthesis.

The use of polyphenol-rich plant extracts is well established for the green synthesis of silver nanoparticles (AgNPs). However, the size of the AgNPs varies substantially depending on the extract used and many researchers report sizes above 20 nm, which are not optimal for antimicrobial activity. Herein, using catechin as a model polyphenol, we have explored two techniques to improve its stabilising capacity and therefore decrease the subsequent AgNP size: cross-linking catechin with sodium tetraborate (borax); and preparation of a water soluble oligomer from catechin (polycat). The prepared AgNPs from the three stabilising systems, cat@AgNPs, cat-borax@AgNPs and polycat@AgNPs, were characterised by UV-Vis spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). Cat-borax produced smaller AgNPs (18.4 nm) than catechin (42.3 nm) but the smallest particles were prepared with polycat (8.5 nm). Antimicrobial efficacy was assessed against Gram positive and Gram negative bacteria and was compared with 10 nm sodium citrate capped AgNPs (citrate@AgNPs). Polycat@AgNPs showed superior antimicrobial activity to cat@AgNPs and cat-borax@AgNPs as well as citrate@AgNPs, exhibiting MICs of only 1.25 µg mL-1 (Ag) for Pseudomonas aeruginosa and Acinetobacter baumannii. Polycat@AgNPs also demonstrated substantially enhanced antibiofilm activity. An Ag concentration of only 5 µg mL-1, was sufficient for a 99.9% reduction in biofilm cell viability and a 99.1% reduction in biofilm biomass with polycat@AgNPs. Uptake of polycat@AgNPs by bacteria was determined to be significantly higher than for citrate@AgNPs and tomographic and SEM images showed evidence of destruction of bacteria cells by polycat@AgNPs.

Laboratory Testing for Von Willebrand Factor Multimers.

Von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders develop due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for the VWF-related disorders requires assessment of both VWF level and VWF activity, the latter requiring multiple assays because of the many functions carried out by VWF to help prevent bleeding. As an additional step, an evaluation of VWF structural features by multimer analysis is useful in selective investigations. The current paper therefore describes a protocol for assessment of VWF multimers by gel electrophoresis, thus enabling identification of protein bands that represent differently sized multimers. The sample protocol described in this chapter is the methodology developed by Sebia.

Tuneable catechin functionalisation of carbohydrate polymers.

In this contribution, we present a strategy to functionalise three natural carbohydrate polymers (dextran - a neutral polymer, sodium alginate - an anionic polymer and chitosan - a cationic polymer) with catechin with excellent degrees of functionality. In a first step, the carbohydrate polymers were oxidised by sodium periodate to yield aldehyde functionalised carbohydrate polymers. The presence of aldehyde groups was exploited to attach catechin by an acid catalysed nucleophilic reaction. The degree of catechin functionalisation could be easily tuned by varying the acid concentration in the reaction mixture, achieving catechin functionalisation levels of up to 48% for dextran aldehyde catechin, 35% for chitosan-aldehyde-catechin and 22% for sodium alginate aldehyde catechin. 1H, 1H-13C HSQC and DOSY NMR were performed to elucidate the structural differences between the three aldehyde functionalised polysaccharides and how this affects their reactivity and conjugation behaviour. All three carbohydrate polymer-catechin conjugates showed superior free-radical scavenging activity compared with the non-functionalised polymers.

Survey on attitudes regarding EULAR recommendations for the role of nurses involved in medical care of patients with chronic inflammatory arthritis in Japan.

OBJECTIVE: We seek to evaluate the opinions of nurses and doctors in Japan regarding EULAR recommendations for nurses' roles in the management of chronic inflammatory arthritis. METHODS: This is a cross-sectional survey within Japan. We randomly selected nurses and doctors engaged in consultation of patients with rheumatoid arthritis (RA) and assessed their agreement and opinions on the feasibility of implementing EULAR recommendations, including potential barriers. RESULTS: 431 nurses and 128 doctors completed the questionnaire. For both nurses and doctors, levels of feasibility showed statistically significant lower results compared with those of agreement for all items. When compared between nurses and doctors, agreement showed no statistically significant differences, while nurses' answers were statistically significant lower for feasibility. Insufficient time, staff and knowledge, lack of established procedures and facilities, and lack of an education system for nurses were cited as barriers to the feasibility of implementing EULAR recommendations. CONCLUSIONS: This is the first survey within Japan evaluating opinions regarding EULAR recommendations for nurses' roles. We found that while agreement was high, feasibility was generally believed to be low. We recommend further research and collaboration between medical professionals in order to implement these recommendations in Japan.

Specialist complex care.

I agree with your editorial on how NHS England and the Department of Health (DH) have failed to realise that specialist care for complex diseases requires experienced and knowledgeable support.