Robust rapid-setting antibacterial liquid bandages

Abstract: Bandaging is a steadfast but time-consuming component of wound care with limited technical advancements to date. Bandages must be changed and infection risk managed. Rapid-set liquid bandages are efficient alternatives but lack durability or inherent infection control. We show here that antibacterial zinc (Zn) and copper (Cu) species greatly enhance the barrier properties of the natural, waterproof, bio-adhesive polymer, shellac. The material demonstrated marked antibacterial contact properties and, in ex-vivo studies, effectively locked-in pre-applied therapeutics. When challenged in vivo with the polybacterial bovine wound infection ‘digital dermatitis’, Zn/Cu-shellac adhered rapidly and robustly over pre-applied antibiotic. The bandage self-degraded, appropriately, over 7 days despite extreme conditions (faecal slurry). Treatment was well-tolerated and clinical improvement was observed in animal mobility. This new class of bandage has promise for challenging topical situations in humans and other animals, especially away from controlled, sterile clinical settings where wounds urgently require protection from environmental and bacterial contamination

Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression

Physiological response of the retinal pigmented epithelium to 3-ns pulse laser application, in vitro and in vivo

BACKGROUND: To treat healthy retinal pigmented epithelium (RPE) with the 3-ns retinal rejuvenation therapy (2RT) laser and to investigate the subsequent wound-healing response of these cells. METHODS: Primary rat RPE cells were treated with the 2RT laser at a range of energy settings. Treated cells were fixed up to 7 days post-irradiation and assessed for expression of proteins associated with wound-healing. For in vivo treatments, eyes of Dark Agouti rats were exposed to laser and tissues collected up to 7 days post-irradiation. Isolated wholemount RPE preparations were examined for structural and protein expression changes. RESULTS: Cultured RPE cells were ablated by 2RT laser in an energy-dependent manner. In all cases, the RPE cell layer repopulated completely within 7 days. Replenishment of RPE cells was associated with expression of the heat shock protein, Hsp27, the intermediate filament proteins, vimentin and nestin, and the cell cycle-associated protein, cyclin D1. Cellular tight junctions were lost in lased regions but re-expressed when cell replenishment was complete. In vivo, 2RT treatment gave rise to both an energy-dependent localised denudation of the RPE and the subsequent repopulation of lesion sites. Cell replenishment was associated with the increased expression of cyclin D1, vimentin and the heat shock proteins Hsp27 and αB-crystallin. CONCLUSIONS: The 2RT laser was able to target the RPE both in vitro and in vivo, causing debridement of the cells and the consequent stimulation of a wound-healing response leading to layer reformation.John P. M. Wood, Marzieh Tahmasebi, Robert J. Casson, Malcolm Plunkett, Glyn Chidlo

Primary squamous cell carcinoma of the rectum: An update and implications for treatment

AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the optimal treatment remains as yet undefined, recent studies have demonstrated a global shift away from surgery towards definitive chemoradiotherapy as primary treatment. Pooled overall survival was calculated to be 86% in patients managed with chemoradiation compared with 48% for those treated traditionally with surgery. Furthermore, local recurrence and metastatic rates were 25% vs 10% and 30% vs 13% for the chemoradiation vs conventional treatment cohorts. CONCLUSION: The changing paradigm in the treatment of rectal SCC holds great promise for improved outcomes in this rare disease

Quantitative evaluation of evaporation rate during spin-coating of polymer blend films: Control of film structure through defined-atmosphere solvent-casting

Thin films of polymer mixtures made by spin-coating can phase separate in two ways: by forming lateral domains, or by separating into distinct layers. The latter situation (self-stratification or vertical phase separation) could be advantageous in a number of practical applications, such as polymer optoelectronics. We demonstrate that, by controlling the evaporation rate during the spin-coating process, we can obtain either self-stratification or lateral phase separation in the same system, and we relate this to a previously hypothesised mechanism for phase separation during spin-coating in thin films, according to which a transient wetting layer breaks up due to a Marangoni-type instability driven by a concentration gradient of solvent within the drying film. Our results show that rapid evaporation leads to a laterally phase-separated structure, while reducing the evaporation rate suppresses the interfacial instability and leads to a self-stratified final film

Voltage-induced swelling and deswelling of weak polybase brushes

We have investigated a novel method of remotely switching the conformation of a weak polybase brush using an applied voltage. Surface-grafted polyelectrolyte brushes exhibit rich responsive behavior and show great promise as “smart surfaces†, but existing switching methods involve physically or chemically changing the solution in contact with the brush. In this study, high grafting density poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes were grown from silicon surfaces using atom transfer radical polymerization. Optical ellipsometry and neutron reflectivity were used to measure changes in the profiles of the brushes in response to DC voltages applied between the brush substrate and a parallel electrode some distance away in the surrounding liquid (water or D2O). Positive voltages were shown to cause swelling, while negative voltages in some cases caused deswelling. Neutron reflectometry experiments were carried out on the INTER reflectometer (ISIS, Rutherford Appleton Laboratory, UK) allowing time-resolved measurements of polymer brush structure. The PDMAEMA brushes were shown to have a polymer volume fraction profile described by a Gaussian-terminated parabola both in the equilibrium and in the partially swollen states. At very high positive voltages (in this study, positive bias means positive voltage to the brush-bearing substrate), the brush chains were shown to be stretched to an extent comparable to their contour length, before being physically removed from the interface. Voltage-induced swelling was shown to exhibit a wider range of brush swelling states in comparison to pH switching, with the additional advantages that the stimulus is remotely controlled and may be fully automated. © 2011, American Chemical Societ

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer

BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging

Multicomponent semiconducting polymer systems with low crystallization-induced percolation threshold

Blends and other multicomponent systems are used in various polymer applications to meet multiple requirements that cannot be fulfilled by a single material. In polymer optoelectronic devices it is often desirable to combine the semiconducting properties of the conjugated species with the excellent mechanical properties of certain commodity polymers. Here we investigate bicomponent blends comprising semicrystalline regioregular poly(3-hexylthiophene) and selected semicrystalline commodity polymers, and show that, owing to a highly favourable, crystallization-induced phase segregation of the two components, during which the semiconductor is predominantly expelled to the surfaces of cast films, we can obtain vertically stratified structures in a one-step process. Incorporating these as active layers in polymer field-effect transistors, we find that the concentration of the semiconductor can be reduced to values as low as 3 wt% without any degradation in device performance. This is in stark contrast to blends containing an amorphous insulating polymer, for which significant reduction in electrical performance was reported. Crystalline-crystalline/semiconducting-insulating multicomponent systems offer expanded flexibility for realizing high-performance semiconducting architectures at drastically reduced materials cost with improved mechanical properties and environmental stability, without the need to design all performance requirements into the active semiconducting polymer itself