pinecone/core-2020-05-10-deduplication huggingface dataset:
Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin

This document is the Accepted Manuscript version of the following article: Lydon, H. L.,??Hall, C. A.,??Dalton, C. H.,??Chipman, J. K.,??Graham, J. S., and??Chilcott, R. P., ???Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agends. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin???, Journal of Applied Toxicology, Vol. 37 (8): 976-984, February 2017. The Version of Record is available online at doi: doi: 10.1002/jat.3446. Copyright ?? 2017 John Wiley & Sons, Ltd.Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 ??m skin layer) resulted in significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat??? was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller???s earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat??? for treating wounds contaminated with CW agents
The percutaneous toxicokinetics of sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat??? as a topical decontaminant

This is the peer reviewed version of the following article: Charlotte A. Hall, et al, 'The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat??? as a topical decontaminant', Journal of Applied Toxicology, July 2017, which has been published in final form at DOI: 10.1002/jat.3453. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Copyright ?? 2017 John Wiley & Sons, Ltd.This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat??? for decontamination of superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 ??L 14C???radiolabelled sulphur mustard (14C???SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat??? was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and organ samples were taken post mortem for histopathological assessment, 14C???SM distribution and toxicokinetic analyses. Application of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration and decreased blood flow at the exposure site in all animals. WoundStat??? prevented ulceration and improved blood flow at the exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of 14C???SM were detected in the blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post-challenge. Overall, the distribution of 14C???SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys, followed by the liver and small intestine. WoundStat??? significantly reduced the amount of 14C???SM recovered from the liver, a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat??? is a suitable product for reducing the ingress and toxicity of a chemical warfare agent
In vitro genotoxicity assessment of an oxidized dextrin-based hydrogel for biomedical applications

Hydrogels are threedimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a lowmolecularweight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrinbased hydrogel (HG). The HG and its components were tested for cyto and genotoxicity according to the International Standard ISO 109933 on the biological evaluation of medical devices. To assess genotoxicity, a battery of in vitro genotoxicity tests employing both eukaryotic and prokaryotic models was performed: comet assay, cytokinesisblock micronucleus assay and Ames test. Our data revealed that the HG (IC50 = 2.8 mg/mL) and oxidized dextrin by itself (IC50 = 1.2 mg/mL) caused a concentrationdependent decrease in cellular viability of human lymphoblastoid TK6 cells after 24 hours of exposure to the test agents. However, these concentrations are unlikely to be reached in vivo. In addition, no significant increase in the DNA and chromosomal damage of TK6 cells exposed to noncytotoxic concentrations of the HG and its isolated components was detected. Furthermore, neither the HG nor its metabolites exerted a mutagenic effect in different of Salmonella typhimurium strains and in an Escherichia coli mix. Our data demonstrated the genocompatibility of the HG (up to 3.5 mg/mL) for biomedical applications. To our best acknowledge, this is the first report with a detailed genotoxicity assessment of an aldehydemodified polysaccharide/adipic acid dihydrazide hydrogel.FEDER ‐ Fundo Europeu de Desenvolvimento Regional. Grant Numbers: NORTE‐01‐0145‐FEDER‐000004, NORTE‐01‐0247‐FEDER‐003262
    Fundação para a Ciência e a Tecnologia. Grant Numbers: PTDC/CTM‐BIO/2170/2014, SFRH/BD/ 90066/2012info:eu-repo/semantics/publishedVersio
Probing for local activity-related modulation of the infrared backscattering of the brain cortex

The possibility to measure the metabolic activity of the brain cortex, with submillimeter spatial and subsecond temporal resolution, would open up enticing scenarios in addressing basic issues on the relation between different structural components of brain signal processing, and in providing an operational pathway to interaction with (dis)functional signal patterns. In the present article, we report the description of a simple system that allows the detection of the minute changes that occur in the optical backscattering of the cortex as a metabolic response to external stimuli. The simplicity of the system is compatible with scalability to an implantable probe. We validate the system on an animal model, and we propose an algorithm to extract meaningful data from the measured signal. We thus show the detection of individual haemodynamic cortical responses to individual stimulation events, and we provide operational considerations on the signal structure
Microvascular and mitochondrial PO 2 simultaneously measured by oxygen-dependent delayed luminescence

Measurement of tissue oxygenation is a complex task and various techniques have led to a wide range of tissue PO 2 values and contradictory results. Tissue is compartmentalized in microcirculation, interstitium and intracellular space and current techniques are biased towards a certain compartment. Simultaneous oxygen measurements in various compartments might be of great benefit for our understanding of determinants of tissue oxygenation. Here we report simultaneous measurement of microvascular PO 2 (μPO 2) and mitochondrial PO 2 (mitoPO 2) in rats. The μPO 2 measurements are based on oxygen-dependent quenching of phosphorescence of the near-infrared phosphor Oxyphor G2. The mitoPO 2 measurements are based on oxygen-dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Favorable spectral properties of these porphyrins allow simultaneous measurement of the delayed luminescence lifetimes. A dedicated fiber-based time-domain setup consisting of a tunable pulsed laser, 2 red-sensitive gated photomultiplier tubes and a simultaneous sampling data-acquisition system is described in detail. The absence of cross talk between the channels is shown and the feasibility of simultaneous μPO 2 and mitoPO 2 measurements is demonstrated in rat liver in vivo. It is anticipated that this novel approach will greatly contribute to our understanding of tissue oxygenation in physiological and pathological circumstances
Total variation versus wavelet‐based methods for image denoising in fluorescence lifetime imaging microscopy

We report the first application of wavelet‐based denoising (noise removal) methods to time‐domain box‐car fluorescence lifetime imaging microscopy (FLIM) images and compare the results to novel total variation (TV) denoising methods. Methods were tested first on artificial images and then applied to low‐light live‐cell images. Relative to undenoised images, TV methods could improve lifetime precision up to 10‐fold in artificial images, while preserving the overall accuracy of lifetime and amplitude values of a single‐exponential decay model and improving local lifetime fitting in live‐cell images. Wavelet‐based methods were at least 4‐fold faster than TV methods, but could introduce significant inaccuracies in recovered lifetime values. The denoising methods discussed can potentially enhance a variety of FLIM applications, including live‐cell,  in vivo  animal, or endoscopic imaging studies, especially under challenging imaging conditions such as low‐light or fast video‐rate imaging. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
Shedding light on diatom photonics by means of digital holography

Diatoms are among the dominant phytoplankters in the world's oceans, and their external silica investments, resembling artificial photonic crystals, are expected to play an active role in light manipulation. Digital holography allowed studying the interaction with light of Coscinodiscus wailesii cell wall reconstructing the light confinement inside the cell cytoplasm, condition that is hardly accessible via standard microscopy. The full characterization of the propagated beam, in terms of quantitative phase and intensity, removed a long-standing ambiguity about the origin of the light confinement. The data were discussed in the light of living cell behavior in response to their environment
Chemically specific imaging and in-situ chemical analysis of articular cartilage with stimulated Raman scattering

This is the pre-peer reviewed version of the following article: Mansfield, J., Moger, J., Green, E., Moger, C. and Winlove, C. P. (2013), Chemically specific imaging and in-situ chemical analysis of articular cartilage with stimulated Raman scattering. J. Biophoton., 6: 803–814. doi: 10.1002/jbio.201200213, which has
been published in final form at http://dx.doi.org/10.1002/jbio.201200213.© 2013 by WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimStimulated Raman scattering (SRS) has been applied to unstained samples of articular cartilage enabling the investigation of living cells within fresh tissue. Hyperspectral SRS measurements over the CH vibrational region showed variations in protein and lipid content within the cells, pericellular matrix and interterritorial matrix. Changes in the cells and pericellular matrix were investigated as a function of depth into the cartilage. Lipid was detected in the pericellular matrix of superficial zone chondrocytes. The spectral profile of lipid droplets within the chondrocytes indicated that they contained predominantly unsaturated lipids. The mineral content has been imaged by using the PO₄³⁻ vibration at 959 cm⁻¹ and the CO₃²⁻ vibration at 1070 cm⁻¹. Both changes in cells and mineralization are known to be important factors in the progression of osteoarthritis. SRS enables these to be visualized in fresh unstained tissue and consequently should benefit osteoarthiritis research
Enabling in vivo measurements of nanoparticle concentrations with three-dimensional optoacoustic tomography

In this report, we demonstrate the feasibility of using optoacoustic tomography (OAT) to evaluate biodistributions of nanoparticles in animal models. The redistribution of single-walled carbon nanotubes (SWCNTs) was visualized in living mice. Nanoparticle concentrations in harvested organs were measured spectroscopically using the intrinsic optical absorption and fluorescence of SWCNTs. Observed increases in optoacoustic signal brightness in tissues were compared with increases in optical absorption coefficients caused by SWCNT accumulation. The methodology presented in this report can further be extended to calibrate the sensitivity of an optoacoustic imaging system for a range of changes in optical absorption coefficient values at specific locations or organs in a mouse body to enable noninvasive measurements of nanoparticle concentrations in vivo. Additionally, qualitative information provided by OAT and quantitative information obtained ex vivo may provide valuable feedback for advancing methods of quantitative analysis with OAT
Localized micro‐scale disruption of cells using laser‐generated focused ultrasound

We utilize laser‐generated focused ultrasound (LGFU) to create targeted mechanical disturbance on a few cells. The LGFU is transmitted through an optoacoustic lens that converts laser pulses into focused ultrasound. The tight focusing (<100 µm) and high peak pressure of the LGFU produces cavitational disturbances at a localized spot with micro‐jetting and secondary shock‐waves arising from micro‐bubble collapse. We demonstrate that LGFU can be used as a non‐contact, non‐ionizing, high‐precision tool to selectively detach a single cell from its culture substrate. Furthermore, we explore the possibility of biomolecule delivery in a small population of cells targeted by LGFU at pressure amplitudes below and above the cavitation threshold. We experimentally confirm that cavitational disruption is required for delivery of propidium iodide, a membrane‐impermeable nucleic acid‐binding dye, into cells. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
M13 Virus based detection of bacterial infections in living hosts

We report a first method for using M13 bacteriophage as a multifunctional scaffold for optically imaging bacterial infections in vivo. We demonstrate that M13 virus conjugated with hundreds of dye molecules (M13-Dye) can target and distinguish pathogenic infections of F- pili expressing and F -negative strains of E. coli. Further, in order to tune this M13-Dye complex suitable for targeting other strains of bacteria, we have used a 1-step reaction for creating an anti-bacterial antibody -M13-Dye probe. As an example, we show anti-S. aureus -M13-Dye able to target and image infections of S. aureus in living hosts, with a 3.7× increase in fluorescence over background.National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5-U54-CA151884-03
Effect of photodynamic therapy on the skin using the ultrashort laser ablation

Photodynamic Therapy (PDT) with 5-aminolevulinic acid (ALA) is known to be limited for applications in tumours of large volume mainly due to the limited penetration of topical photosensitization. The results show that micro-holes created using a femtosecond laser before PDT significantly increased the depth of PDT effect in the healthy tissue. The combination of ultrashort laser ablation technique with PDT showed an important scientific breakthrough related to transportation and delivery of drugs into the deeper regions of the tissue.FAPESP (CePOF/CEPID)CNPq (INCT)CAPE
A Raman spectroscopy bio-sensor for tissue discrimination in surgical robotics

We report the development of a fiber-based Raman sensor to be used in tumour margin identification during endoluminal robotic surgery. Although this is a generic platform, the sensor we describe was adapted for the ARAKNES (Array of Robots Augmenting the KiNematics of Endoluminal Surgery) robotic platform. On such a platform, the Raman sensor is intended to identify ambiguous tissue margins during robot-assisted surgeries. To maintain sterility of the probe during surgical intervention, a disposable sleeve was specially designed. A straightforward user-compatible interface was implemented where a supervised multivariate classification algorithm was used to classify different tissue types based on specific Raman fingerprints so that it could be used without prior knowledge of spectroscopic data analysis. The protocol avoids inter-patient variability in data and the sensor system is not restricted for use in the classification of a particular tissue type. Representative tissue classification assessments were performed using this system on excised tissue
Multimodal and multiplex spectral imaging of rat cornea ex vivo using a white-light laser source

Multimodal nonlinear spectral images of rat cornea at corneal epithelium and corneal stroma in the in-plane (XY) direction. With use of the combinational analysis of different nonlinear optical processes, detailed molecular structural information is available without staining or labelling.We applied our multimodal nonlinear spectral imaging microscope to the measurement of rat cornea. We successfully obtained multiple nonlinear signals of coherent anti-Stokes Raman scattering (CARS), third-order sum frequency generation (TSFG), and second harmonic generation (SHG). Depending on the nonlinear optical processes, the cornea tissue was visualized with different image contrast mechanism simultaneously. Due to white-light laser excitation, multiplex CARS and TSFG spectra were obtained. Combined multimodal and spectral analysis clearly elucidated the layered structure of rat cornea with molecular structural information. This study indicates that our multimodal nonlinear spectral microscope is a promising bioimaging method for tissue study
Recent advances in optical fiber devices for microfluidics integration

This paper examines the recent emergence of miniaturized optical fiber based sensing and actuating devices that have been successfully integrated into fluidic microchannels that are part of microfluidic and lab-on-chip systems. Fluidic microsystems possess the advantages of reduced sample volumes, faster and more sensitive biological assays, multi-sample and parallel analysis, and are seen as the de facto bioanalytical platform of the future. This paper considers the cases where the optical fiber is not merely used as a simple light guide delivering light across a microchannel, but where the fiber itself is engineered to create a new sensor or tool for use within the environment of the fluidic microchannel
Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source

Multicolor multiphoton microscopy is experimentally demonstrated for the first time on a spectral bandwidth of excitation of 300 nm (full width half maximum) thanks to the implementation a nanosecond supercontinuum (SC) source compact and simple with a low repetition rate. The interest of such a wide spectral bandwidth, never demonstrated until now, is highlighted in vivo: images of glioma tumor cells stably expressing eGFP grafted on the brain of a mouse and its blood vessels network labelled with Texas Red® are obtained. These two fluorophores have a spectral bandwidth covering the whole 300 nm available. In parallel, a similar image quality is obtained on a sample of mouse muscle in vitro when excited with this nanosecond SC source or with a classical high rate, femtosecond and quasi monochromatic laser. This opens the way for (i) a simple and very complete biological characterization never performed to date with multiphoton processes, (ii) multiple means of contrast in nonlinear imaging allowed by the use of numerous fluorophores and (iii) other multiphoton processes like three-photon ones
Tunable fibre-coupled multiphoton microscopy with a negative curvature fibre

Negative curvature fibre (NCF) guides light in its core by inhibiting the coupling of core and cladding modes. In this work, an NCF was designed and fabricated to transmit ultrashort optical pulses for multiphoton microscopy with low group velocity dispersion (GVD) at 800 nm. Its attenuation was measured to be <0.3 dB m(-1) over the range 600-850 nm and the GVD was -180 ± 70 fs(2)  m(-1) at 800 nm. Using an average fibre output power of ∼20 mW and pulse repetition rate of 80 MHz, the NCF enabled pulses with a duration of <200 fs to be transmitted through a length of 1.5 m of fibre over a tuning range of 180 nm without the need for dispersion compensation. In a 4 m fibre, temporal and spectral pulse widths were maintained to within 10% of low power values up to the maximum fibre output power achievable with the laser system used of 278 mW at 700 nm, 808 mW at 800 nm and 420 mW at 860 nm. When coupled to a multiphoton microscope, it enabled imaging of ex vivo tissue using excitation wavelengths from 740 nm to 860 nm without any need for adjustments to the set-up
easySTORM: a robust, lower-cost approach to localisation and TIRF microscopy

TIRF and STORM microscopy are super-resolving fluorescence imaging modalities for which current implementations on standard microscopes can present significant complexity and cost. We present a straightforward and low-cost approach to implement STORM and TIRF taking advantage of multimode optical fibres and multimode diode lasers to provide the required excitation light. Combined with open source software and relatively simple protocols to prepare samples for STORM, including the use of Vectashield for non-TIRF imaging, this approach enables TIRF and STORM imaging of cells labelled with appropriate dyes or expressing suitable fluorescent proteins to become widely accessible at low cost
Screening the low molecular weight fraction of human serum using ATR-IR spectroscopy

Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. Spectroscopic detection of potential serum biomarkers present at relatively low concentrations can be improved using pre-analytical depletion of the HMWF. In the present study, human serum fractionation by centrifugal filtration was used prior to analysis by Attenuated Total Reflection infrared spectroscopy. Using a model sample based on glycine spiked serum, it is demonstrated that the screening of the LMWF can be applied to quantify blinded concentrations up to 50 times lower. Moreover, the approach is easily transferable to different bodily fluids which would support the development of more efficient and suitable clinical protocols exploring vibrational spectroscopy based ex-vivo diagnostic tools