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    Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions

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    Percutaneous thermal ablation has proven to be an effective modality for treating both benign and malignant tumours in various tissues. Among these modalities, radiofrequency ablation (RFA) is the most promising and widely adopted approach that has been extensively studied in the past decades. Microwave ablation (MWA) is a newly emerging modality that is gaining rapid momentum due to its capability of inducing rapid heating and attaining larger ablation volumes, and its lesser susceptibility to the heat sink effects as compared to RFA. Although the goal of both these therapies is to attain cell death in the target tissue by virtue of heating above 50°C, their underlying mechanism of action and principles greatly differs. Computational modelling is a powerful tool for studying the effect of electromagnetic interactions within the biological tissues and predicting the treatment outcomes during thermal ablative therapies. Such a priori estimation can assist the clinical practitioners during treatment planning with the goal of attaining successful tumour destruction and preservation of the surrounding healthy tissue and critical structures. This review provides current state-of-the-art developments and associated challenges in the computational modelling of thermal ablative techniques, viz., RFA and MWA, as well as touch upon several promising avenues in the modelling of laser ablation, nanoparticles assisted magnetic hyperthermia and non-invasive RFA. The application of RFA in pain relief has been extensively reviewed from modelling point of view. Additionally, future directions have also been provided to improve these models for their successful translation and integration into the hospital work flow

    Bio-phenol formaldehyde (BPF) resoles prepared using phenolic extracts from the biocrude oils derived from hydrothermal liquefaction of hydrolysis lignin

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    In this work, hydrolysis lignin, as a low-value feedstock, was liquefied in ethanol/water co-solvents (50:50, v/v) at 350 °C for 30 min, with or without the use of hematite ore as the catalyst. Following this, the resulting bio-crude oil was applied as the feedstock for the preparation of neat phenol formaldehyde (PF) resole and bio-phenol formaldehyde (BPF) resoles. The net PF resole was prepared by using the whole bio-crude oil, while, the phenolic extracts from the crude oil together with 50% of phenol were employed for the preparation of BPF resoles. The results displayed that although the BPF resole contained a higher free formaldehyde and less thermally stable than neat PF resole, a lower curing temperature was adopted for BPF resole compared to neat PF resole. By analyzing their physical properties, it was observed that the dry bonding strength of BPF resoles was higher than that of neat PF resole. Most importantly, the dry and wet strengths of BPF resole met the requirements for using as an adhesive for plywood bonding. Overall, it can be concluded that the bio-crude oil-derived phenolic extracts from HTL of hydrolysis lignin is a suitable feedstock for producing value-added BPF with potential use as a wood adhesive.Natural Sciences and Engineering Research Council of Canada (NSERC)Natural Scientific Foundation of Chin

    Alkali-catalyzed liquefaction of pinewood sawdust in ethanol/water co-solvents

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    In this study, pinewood sawdust was liquefied in either ethanol/water co-solvents (50/50, wt./wt.) or pure water at 300 °C for 30 min and 10 wt% of feedstock loading, with or without the use of Na2CO3 or NaOH as a catalyst. The physical and chemical properties of liquefaction products (bio-crude oil and solid residue) were comprehensively characterized by FT-IR, GC-MS, elemental, GPC and TGA analyses. The results showed that the highest biomass conversion of approx. 98% was obtained in ethanol/water mixed solvents and without catalyst, along with a maximum yield of bio-crude oil (~48 wt%). The HHV of crude oil was within the range of 26–30 MJ/kg. The results indicated that the beneficial effect of ethanol on the bio-crude oil yield might be compromised by adding Na2CO3 or NaOH into the liquefaction system under investigated reaction conditions. As suggested by GPC analysis, the bio-crude oil obtained in ethanol/water co-solvents from both non-catalytic and catalytic liquefaction contained a slightly higher molecular weight than that obtained in pure water. Additionally, TGA results indicated that the boiling point distribution of bio-crude oil was only affected by ethanol addition, whereas, the effect of the catalyst was found to be minor.Natural Sciences and Engineering Research Council (NSERC)MITACSGreenfield Global In

    Discovery of a isothiazolinone-containing antitubercular natural product levesquamide

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    Antitubercular agent levesquamide is a new polyketide-nonribosomal peptide (PK-NRP) hybrid marine natural product isolated from Streptomyces sp. RKND-216. The structure contains a rare isothiazolinone moiety which has only been reported in collismycin SN. Structure elucidation by NMR spectroscopy was a significant challenge due to a deficiency of protons in this aromatic moiety. Therefore, the genome of Streptomyces sp. RKND-216 was sequenced to identify the levesquamide biosynthetic gene cluster (BGC). Analysis of the BGC provided structural insights and guided stable-isotope labeling experiments, which led to the assignment of the fused pyridine-isothiazolinone moiety. The BGC and the labeling experiments provide further insights into the biosynthetic origin of isothiazolinones. Levesquamide exhibited antimicrobial activity in the microplate alamarBlue assay (MABA) and low oxygen recovery assay (LORA) against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 9.65 and 22.28 μM, respectively. Similar activity was exhibited against rifampicin- and isoniazid-resistant M. tuberculosis strains with MIC values of 9.46 and 9.90 μM, respectively. This result suggests levesquamide has a different mode of action against M. tuberculosis compared to the two first-line antitubercular drugs rifampicin and isoniazid. Furthermore, levesquamide shows no cytotoxicity against the Vero cell line, suggesting it may have a useful therapeutic windo

    Cyclin D1 immunohistochemical expression and somatic mutations in canine oral melanoma

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    Canine oral melanoma (COM) is the most frequent tumour with oral localization in dogs. Copy number gains and amplifications of CCND1, a gene coding for Cyclin D1, are the most frequent chromosomal aberrations described in human non-UV induced melanomas. Twenty-eight cases of COM were retrieved from paraffin-blocks archives. A total of 4 μm thick sections were immunostained with an antibody against human Cyclin D1 and Ki-67. Cyclin D1 and Ki-67 expressions were scored through two counting methods. DNA was extracted from 20 μm thick sections of formalin-fixed paraffin-embedded blocks. Pathological and surrounding healthy tissue was extracted independently. Cyclin D1 immunolabelling was detected in 69% (18/26) while Ki-67 was present in 88.5% (23/26) of cases. Statistical analysis revealed correlation between two counting methods for Cyclin D1 (r = 0.54; P = .004) and Ki-67 (r = 0.56; P = .003). The correlation found between Ki-67 and Cyclin D1 indexes in 16/26 cases labelled by both antibodies (r = 0.7947; P = .0002) suggests a possible use of Cyclin D1 index as prognostic marker. Polymerase chain reaction analysis on CCND1 coding sequence revealed the presence of nine somatic mutations in seven samples producing synonymous, missense and stop codons. Since none of the single-nucleotide polymorphisms was found to be recurrent, it is suggested that overexpression of Cyclin D1 may be the consequence of alterations of CCND1 upstream regions or other genetic aberrations not detectable with the methodology used in this study. Future studies are needed to verify the potential use of Cyclin D1 index as prognostic indicator and to highlight the molecular events responsible for Cyclin D1 overexpression in COMs

    Biocompatibility of allogenic canine fascia lata: In vitro evaluation and small case series

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    Objective To evaluate the biocompatibility of canine fascia lata (FL) in vitro and after FL allograft implantation in dogs with clinical disease. Study design In vitro experiment and small case series. Sample population Six dogs treated with allogenic freeze-dried FL. Methods Fibroblasts were cultured on disks of FL, polypropylene mesh (PM; negative control), and porcine small intestinal submucosa (SIS; positive control). Constructs were compared at 3, 7, and 14 days for water content, DNA amounts, scanning electron microscopy, and histology. Records of dogs treated with FL allografts with follow-up examination were reviewed for signalment, indication for surgery, surgical procedure, and outcomes. All owners were invited to complete a standardized questionnaire for long-term follow-up. Results Water content was greater in FL and SIS than in PM (P = .03). Fascia lata constructs contained more DNA compared with PM constructs at days 7 and 14 (P < .05), whereas SIS constructs did not differ from FL or PM. Fibroblasts appeared spherical and distributed throughout FL constructs, whereas they appeared stellate and remained on the surface of SIS and PM. Fascia lata allografts were implanted in six dogs with surgical conditions. No incisional complications were noted. All dogs had good to excellent long-term outcomes, except one that experienced recurrence of a perineal hernia 2 years after repair. Conclusion In vitro, canine FL allowed attachment and proliferation of fibroblasts throughout layers of the graft. Canine allogenic FL was clinically well tolerated in this small population of dogs. Clinical significance Allogenic FL is biocompatible and can be considered an alternative to SIS for soft tissue augmentation in dogs

    Optimization of starch- and chitosan-based bio-inks for 3D bioprinting of scaffolds for neural cell growth

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    This paper investigates the use of starch and chitosan blends for bioprinting of neural cell applications. The printability and biocompatibility of different starch to chitosan ratio bio-inks were studied. The biofabrication window paradigm was used to determine the optimum composition of bio-ink as 50% starch and 50% chitosan in terms of both printability and biocompatibility with Neuro-2a cells. This defies the conventional understanding that increasing the chitosan percentage enhances the biocompatibility. Moreover, the limitations of the conventional framework for characterizing the printability of bio-inks were identified and a revised framework based on the flattening factor was proposed. It was shown that the revised framework provides better means of characterizing the printability of bio-inks

    Mechanisms of Naphthenic Acid Toxicity

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    The Alberta Oil Sands are the third largest reserve of crude oil in the world. Most of this oil is extracted via the Clarke hot water extraction process, producing large volumes of waste water or oil sands process-affected water (OSPW). This water must be kept on oil sands sites, resulting in the creation of large tailings ponds. These ponds contain numerous toxic compounds, one of the principle ones being naphthenic acids (NAs). These are carboxylic acids that are natural components of petroleum and are thought to be responsible for much of the toxicity of tailings ponds. They have been shown to be acutely lethal and have a number of sublethal effects to a variety of aquatic organisms and other species. Despite the wide knowledge of their toxic effects, the mechanism of toxic action of naphthenic acids has remained elusive. Based on the known mechanisms of resin acids, carboxylic acids from pulp and paper mill effluent, it was hypothesized that naphthenic acids would disrupt mitochondrial energetics by uncoupling oxidative phosphorylation (OXPHOS) and inhibiting the electron transport system (ETS), which would result in oxidative stress and increased reactive oxygen species (ROS). For this thesis, NAs were extracted and purified from a 17-year-old tailings pond yielding a mixture containing 99% carboxylic acids with 90% fitting the classical NA formula (CnH2n+ZO2). Mitochondria were isolated from rainbow trout (Oncorhynchus mykiss) livers via differential centrifugation and the mitochondrial oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide production were measured simultaneously using the Oroboros respirometry system following exposure to different doses of the OSPW-NA mixture. Mitochondrial membrane potential and oxidation state were also measured using real-time flow cytometry methods using fluorescent dyes, JC-1 and H2DCFDA, respectively. The effects of two model adamantane NAs, 3,5-dimethyladamantane-1-carboxylic acid and 3-hydroxy-adamantane-1-carboxylic acids, were also examined to determine if they could be used as surrogate toxicants for an NA mixture. The results showed that NAs derived from OSPW inhibited mitochondrial respiration and increased ROS. Oxidative uncoupling of the mitochondria also occurred, but to a lesser degree than the other effects. The EC50 and IC50 values calculated for the endpoints were consistent with NA levels found in tailings ponds, while the estimated EC10 and IC10 values approach environmental concentrations of NAs. The model adamantane acids that were examined showed some similar effects to the OSPW-NA mixture, suggesting that some adamantane compounds may be able to act as surrogates for oil sands-derived NAs. In conclusion, the mechanism of action of NAs appears to be complex and they likely act via multiple mechanisms, wherein mitochondria may be an important target

    Tasting Place: Themes in food and beverage product logos from three North Atlantic island regions

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    Islands have long been romanticized for their potential to facilitate the kind of escape from globalization increasingly sought by neolocalism-driven consumers, and are thus uniquely positioned to emphasize their distinctive environment and culture through a holistic destination brand that targets both the tourism and local product markets. The current study examines the relationship between destination brands and local food and beverage brands in three North Atlantic island regions: Newfoundland, Iceland, and Shetland. Using a blend of content and thematic analysis to identify and analyze prominent themes employed in product logos, this study offers insight regarding food and beverage branding approaches in island contexts and their relationship to regional destination brands. Throughout the content examined for this study, island-based food and beverage producers demonstrated an intense and dynamic connection to place, as exemplified through the themes of place, culture, and environment embedded in their logos. Discussion of the study findings highlights the importance of strong logo branding for entrepreneurial success and regional tourism promotion, and advocates for future research and practical implementation of effective branding and logo design

    Identification of critical enzymes in the salmon louse chitin synthesis pathway as revealed by RNA interference-mediated abrogation of infectivity

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    Treatment of infestation by the ectoparasite Lepeophtheirus salmonis relies on a small number of chemotherapeutant treatments that currently meet with limited success. Drugs targeting chitin synthesis have been largely successful against terrestrial parasites where the pathway is well characterised. However, a comparable approach against salmon lice has been, until recently, less successful, likely due to a poor understanding of the chitin synthesis pathway. Post-transcriptional silencing of genes by RNA interference (RNAi) is a powerful method for evaluation of protein function in non-model organisms and has been successfully applied to the salmon louse. In the present study, putative genes coding for enzymes involved in L. salmonis chitin synthesis were characterised after knockdown by RNAi. Nauplii I stage L. salmonis were exposed to double-stranded (ds) RNA specific for several putative non-redundant points in the pathway: glutamine: fructose-6-phosphate aminotransferase (LsGFAT), UDP-N-acetylglucosamine pyrophosphorylase (LsUAP), N-acetylglucosamine phosphate mutase (LsAGM), chitin synthase 1 (LsCHS1), and chitin synthase 2 (LsCHS2). Additionally, we targeted three putative chitin deacetylases (LsCDA4557, 5169 and 5956) by knockdown. Successful knockdown was determined after moulting to the copepodite stage by real-time quantitative PCR (RT-qPCR), while infectivity potential (the number of attached chalimus II compared with the initial number of larvae in the system) was measured after exposure to Atlantic salmon and subsequent development on their host. Compared with controls, infectivity potential was not compromised in dsAGM, dsCHS2, dsCDA4557, or dsCDA5169 groups. In contrast, there was a significant effect in the dsUAP-treated group. However, of most interest was the treatment with dsGFAT, dsCHS1, dsCHS1+2, and dsCDA5956, which resulted in complete abrogation of infectivity, despite apparent compensatory mechanisms in the chitin synthesis pathway as detected by qPCR. There appeared to be a common phenotypic effect in these groups, characterised by significant aberrations in appendage morphology and an inability to swim. Ultrastructurally, dsGFAT showed a significantly distorted procuticle without distinct exo/endocuticle and intermittent electron dense (i.e. chitin) inclusions, and together with dsUAP and dsCHS1, indicated delayed entry to the pre-moult phase.Natural Sciences and Engineering Research Council of CanadaThe Research Council of NorwayCanada Excellence Research ChairsThe Directorate for Internationalization and Quality Development in Higher EducationNorwegian Agency for International Cooperation and Quality Enhancement in Higher Educatio

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