Publications by authors named "Sam Murray"

31 Publications

Chemical Emissions from Cured and Uncured 3D-Printed Ventilator Patient Circuit Medical Parts.

ACS Omega 2021 Nov 8;6(45):30726-30733. Epub 2021 Nov 8.

Aerodyne Research, Inc., 45 Manning Road, Billerica, Massachusetts 01821, United States.

Medical shortages during the COVID-19 pandemic saw numerous efforts to 3D print personal protective equipment and treatment supplies. There is, however, little research on the potential biocompatibility of 3D-printed parts using typical polymeric resins as pertaining to volatile organic compounds (VOCs), which have specific relevance for respiratory circuit equipment. Here, we measured VOCs emitted from freshly printed stereolithography (SLA) replacement medical parts using proton transfer reaction mass spectrometry and infrared differential absorption spectroscopy, and particulates using a scanning mobility particle sizer. We observed emission factors for individual VOCs ranging from ∼0.001 to ∼10 ng cm min. Emissions were heavily dependent on postprint curing and mildly dependent on the type of SLA resin. Curing reduced the emission of all observed chemicals, and no compounds exceeded the recommended dose of 360 μg/d. VOC emissions steadily decreased for all parts over time, with an average -folding time scale (time to decrease to 1/ of the starting value) of 2.6 ± 0.9 h.
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http://dx.doi.org/10.1021/acsomega.1c04695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600644PMC
November 2021

Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

J Immunother Cancer 2021 09;9(9)

Department of Oncology, University of Milan, Milano, Italy.

Background: Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.

Methods: We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163.

Results: We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-.

Conclusions: TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
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http://dx.doi.org/10.1136/jitc-2021-003311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487214PMC
September 2021

Update of the Planktonic Diatom Genus in Aotearoa New Zealand Coastal Waters: Genetic Diversity and Toxin Production.

Toxins (Basel) 2021 09 10;13(9). Epub 2021 Sep 10.

Cawthron Institute, Nelson 7010, New Zealand.

Domoic acid (DA) is produced by almost half of the species belonging to the diatom genus and causes amnesic shellfish poisoning (ASP). It is, therefore, important to investigate the diversity and toxin production of species for ASP risk assessments. Between 2018 and 2020, seawater samples were collected from various sites around Aotearoa New Zealand, and 130 clonal isolates of were established. Molecular phylogenetic analysis of partial large subunit ribosomal DNA and/or internal transcribed spacer regions revealed that the isolates were divided into 14 species (, , , , , , , , , , , , , and cf. ). The and strains were further divided into two clades/subclades (I and II). Liquid chromatography-tandem mass spectrometry was used to assess the production of DA and DA isomers by 73 representative strains. The analyses revealed that two ( and ) of the 14 species produced DA as a primary analogue, along with several DA isomers. This study is the first geographical distribution record of , , , and in New Zealand coastal waters.
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http://dx.doi.org/10.3390/toxins13090637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473122PMC
September 2021

Immunotherapy in Hepatocellular Carcinoma.

Curr Treat Options Oncol 2021 08 23;22(10):87. Epub 2021 Aug 23.

Department of Surgery & Cancer, Hammersmith Hospital, Imperial College London, Hammersmith Campus, Du Cane Road, W120HS, London, UK.

Opinion Statement: Patients with hepatocellular carcinoma (HCC) have been traditionally deprived from highly effective systemic therapy options in the past decades. The multi-targeted tyrosine kinase inhibitor sorafenib, approved in 2008, remained the only treatment option for advanced HCC for over a decade. A number of molecularly targeted therapies such as lenvatinib, regorafenib, cabozantinib, and ramucirumab have significantly widened treatment options in patients with advanced HCC. However, emergence of resistance and long-term toxicity from treatment are barriers to long-term survivorship. Immunotherapy is at the focus of intense research efforts in HCC. Whilst targeting of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte 4 (CTLA-4) is associated with radiologically measurable disease-modulating effects in HCC, monotherapies fell short of demonstrating evidence of significant survival extension in advanced disease. Atezolizumab and bevacizumab were the first immunotherapy regimen to demonstrate clear superiority in improving the survival of patients with unresectable HCC compared to sorafenib, paving the way for immunotherapy combinations. As the treatment landscape of HCC rapidly evolves, with immunotherapy integrating within early- and intermediate-stage disease treatment algorithms, lack of level 1 evidence on sequencing of therapeutic strategies and lack of head-to-head comparisons across immunotherapy combinations will affect prescribing of immunotherapy in routine practice. In the absence of predictive biomarkers, choice of immunotherapy over kinase inhibitors will continue to remain an empirical exercise, guided by balancing anti-tumour efficacy with toxicity considerations in the individual patient.
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http://dx.doi.org/10.1007/s11864-021-00886-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382645PMC
August 2021

Ciguatera poisoning and confirmation of ciguatoxins in fish imported into New Zealand.

N Z Med J 2021 06 4;134(1536):100-104. Epub 2021 Jun 4.

Seafood Safety Research Programme Leader; NZ Food Safety Science & Research Centre Deputy Director, Cawthron Institute, 98 Halifax Street East, PB 2, Nelson, New Zealand.

Ciguatera poisoning has caused illnesses in New Zealand through the consumption of contaminated reef fish imported from Pacific Islands. In May 2020 five people became ill and one was hospitalised following the consumption of Fiji Kawakawa (camouflage grouper; Epinephelus polyphekadion). The fish was purchased in New Zealand but imported from Fiji. The meal remnants were analysed for ciguatoxins, the causative compounds of ciguatera poisoning, and showed the presence of the three main toxic fish metabolites. Other fish tested from the same shipment did not contain detectable levels of ciguatoxins, indicating they were likely not toxic.
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June 2021

Acute Toxicity of Gambierone and Quantitative Analysis of Gambierones Produced by Cohabitating Benthic Dinoflagellates.

Toxins (Basel) 2021 05 5;13(5). Epub 2021 May 5.

School of Science, University of Waikato, Private Bag 3105, Hamilton 3240, New Zealand.

Understanding the toxicity and production rates of the various secondary metabolites produced by and cohabitating benthic dinoflagellates is essential to unravelling the complexities associated with ciguatera poisoning. In the present study, a sulphated cyclic polyether, gambierone, was purified from CAWD232 and its acute toxicity was determined using intraperitoneal injection into mice. It was shown to be of low toxicity with an LD of 2.4 mg/kg, 9600 times less toxic than the commonly implicated Pacific ciguatoxin-1B, indicating it is unlikely to play a role in ciguatera poisoning. In addition, the production of gambierone and 44-methylgambierone was assessed from 20 isolates of ten , two and two species using quantitative liquid chromatography-tandem mass spectrometry. Gambierone was produced by seven species, ranging from 1 to 87 pg/cell, and one species from each of the genera and , ranging from 2 to 17 pg/cell. The production of 44-methylgambierone ranged from 5 to 270 pg/cell and was ubiquitous to all species tested, as well as both species of and . The relative production ratio of these two secondary metabolites revealed that only two species produced more gambierone, CAWD237 and CAWD232. This represents the first report of gambierone acute toxicity and production by these cohabitating benthic dinoflagellate species. While these results demonstrate that gambierones are unlikely to pose a risk to human health, further research is required to understand if they bioaccumulate in the marine food web.
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http://dx.doi.org/10.3390/toxins13050333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147941PMC
May 2021

Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2.

NPJ Vaccines 2021 May 13;6(1):74. Epub 2021 May 13.

Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.

As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.
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http://dx.doi.org/10.1038/s41541-021-00336-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116645PMC
May 2021

Chlamydia trachomatis: Cell biology, immunology and vaccination.

Vaccine 2021 05 24;39(22):2965-2975. Epub 2021 Mar 24.

Department of Infectious Diseases, Imperial College London, Norfolk Place, London W2 1PG, UK. Electronic address:

Chlamydia trachomatis is the causative agent of a highly prevalent sexually transmitted bacterial disease and is associated with a number of severe disease complications. Current therapy options are successful at treating disease, but patients are left without protective immunity and do not benefit the majority asymptomatic patients who do not seek treatment. As such, there is a clear need for a broad acting, protective vaccine that can prevent transmission and protect against symptomatic disease presentation. There are three key elements that underlie successful vaccine development: 1) Chlamydia biology and immune-evasion adaptations, 2) the correlates of protection that prevent disease in natural and experimental infection, 3) reflection upon the evidence provided by previous vaccine attempts. In this review, we give an overview of the unique intra-cellular biology of C. trachomatis and give insight into the dynamic combination of adaptations that allow Chlamydia to subvert host immunity and survive within the cell. We explore the current understanding of chlamydial immunity in animal models and in humans and characterise the key immune correlates of protection against infection. We discuss in detail the specific immune interactions involved in protection, with relevance placed on the CD4+ T lymphocyte and B lymphocyte responses that are key to pathogen clearance. Finally, we provide a timeline of C. trachomatis vaccine research to date and evaluate the successes and failures in development so far. With insight from these three key elements of research, we suggest potential solutions for chlamydial vaccine development and promising avenues for further exploration.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.043DOI Listing
May 2021

In vitro investigation of the genotoxicity of portimine, a cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, on human hepatic HepaRG cells.

Toxicol In Vitro 2021 Jun 22;73:105125. Epub 2021 Feb 22.

Agence Nationale de Sécurité Sanitaire (ANSES), Unité de Toxicologie des Contaminants, 10 B rue Claude Bourgelat, 35306 Fougères, France. Electronic address:

Portimine, a recently identified cyclic imine produced by the dinoflagellate Vulcanodinium rugosum, has been described as a potent apoptotic agent in contrast to most of the cyclic imines that are well-known to be neurological toxins. As apoptosis can be a consequence of a high level of DNA lesions, we investigated the responses of portimine on several endpoints aimed at detecting DNA damage in the hepatic cell line HepaRG. Portimine induced phosphorylation of H2AX, which could possibly be consistent with the previously published induction of apoptosis with this toxin. In addition, detection of apoptosis through the activation of caspase-3, the induction of strand breaks detected by the comet assay as well as chromosome and genome mutations using the micronucleus assay were addressed. Surprisingly, portimine treatment resulted in increases in only γH2AX in differentiated HepaRG cells whereas no effects on the other endpoints were detected. These increases in γH2AX in the absence of genotoxic effects in the other tests could indicate that portimine could possibly induce a DNA replication stress and/or that the compound can be detoxified by the HepaRG cells.
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http://dx.doi.org/10.1016/j.tiv.2021.105125DOI Listing
June 2021

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.

Sci Immunol 2020 12;5(54)

National Infection Service, Public Health England, Porton Down, UK.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
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http://dx.doi.org/10.1126/sciimmunol.abf3698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101131PMC
December 2020

Acute toxicity of dihydroanatoxin-a from Microcoleus autumnalis in comparison to anatoxin-a.

Chemosphere 2021 Jan 13;263:127937. Epub 2020 Aug 13.

AgResearch Limited, Ruakura Research Centre, Private Bag 3123, Hamilton, 3240, New Zealand.

The cyanobacterium Microcoleus autumnalis grows as thick benthic mats in rivers and is becoming increasingly prevalent around the world. M. autumnalis can produce high concentrations of anatoxins and ingestion of benthic mats has led to multiple dog deaths over the past two decades. M. autumnalis produces a suite of different anatoxin congeners including anatoxin-a (ATX), dihydroanatoxin-a, (dhATX), homoanatoxin-a and dihydrohomoanatoxin-a. Benthic mat samples often contain high levels of dhATX, but there is little toxicology information on this congener. In the present study, natural versions of dhATX and ATX were purified from cyanobacteria to determine the acute toxicity by different routes of administration using mice. Nuclear magnetic resonance spectroscopy was used to confirm the putative structure of dhATX. By intraperitoneal (ip) injection, the median lethal dose (LD) for dhATX was 0.73 mg/kg, indicating a reduced toxicity compared to ATX (LD of 0.23 mg/kg). However, by oral administration (both gavage and feeding), dhATX was more toxic than ATX (gavage LD of 2.5 mg/kg for dhATX and 10.6 mg/kg for ATX; feeding LD of 8 mg/kg for dhATX and 25 mg/kg for ATX). The relative nicotinic acetylcholine receptor-binding affinities of ATX and dhATX were determined using the Torpedo electroplaque assay which showed consistency with the relative toxicity determined by ip injection. This work highlights that toxicity studies based solely on ip injection may not yield LD values that are relevant to those derived via oral administration, and hence, do not provide a good estimate of the risk posed to human and animal health in situations where oral ingestion is the likely route of exposure. The high acute oral toxicity of dhATX, and its abundance in M. autumnalis proliferations, demonstrates that it is an important environmental contaminant that warrants further investigation.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127937DOI Listing
January 2021

The role of 44-methylgambierone in ciguatera fish poisoning: Acute toxicity, production by marine microalgae and its potential as a biomarker for Gambierdiscus spp.

Harmful Algae 2020 07 19;97:101853. Epub 2020 Jun 19.

School of Science, University of Waikato, Private Bag 3105, Hamilton 3240, New Zealand.

Ciguatera fish poisoning (CFP) is prevalent around the tropical and sub-tropical latitudes of the world and impacts many Pacific island communities intrinsically linked to the reef system for sustenance and trade. While the genus Gambierdiscus has been linked with CFP, it is commonly found on tropical reef systems in microalgal assemblages with other genera of toxin-producing, epiphytic and/or benthic dinoflagellates - Amphidinium, Coolia, Fukuyoa, Ostreopsis and Prorocentrum. Identifying a biomarker compound that can be used for the early detection of Gambierdiscus blooms, specifically in a mixed microalgal community, is paramount in enabling the development of management and mitigation strategies. Following on from the recent structural elucidation of 44-methylgambierone, its potential to contribute to CFP intoxication events and applicability as a biomarker compound for Gambierdiscus spp. was investigated. The acute toxicity of this secondary metabolite was determined by intraperitoneal injection using mice, which showed it to be of low toxicity, with an LD between 20 and 38 mg kg. The production of 44-methylgambierone by 252 marine microalgal isolates consisting of 90 species from 32 genera across seven classes, was assessed by liquid chromatography-tandem mass spectrometry. It was discovered that the production of this secondary metabolite was ubiquitous to the eight Gambierdiscus species tested, however not all isolates of G. carpenteri, and some species/isolates of Coolia and Fukuyoa.
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http://dx.doi.org/10.1016/j.hal.2020.101853DOI Listing
July 2020

Hemolysis associated toxicities of benthic dinoflagellates from Hong Kong waters.

Mar Pollut Bull 2020 Jun 27;155:111114. Epub 2020 Apr 27.

State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Chemistry, City University of Hong Kong, Hong Kong, China. Electronic address:

Benthic dinoflagellates produce a diverse range of phycotoxins, which are responsible for intoxication events in marine fauna. This study assessed the hemolysis associated toxicities of six species of benthic dinoflagellates from the genera Coolia, Fukuyoa, Amphidinium and Prorocentrum. Results demonstrated that Amphidinium carterae, Coolia tropicalis and Fukuyoa ruetzleri were the three most toxic species, while Prorocentrum cf. lima did not have significant hemolytic effect. Grouper samples (Cephalopholis boenak) were more tolerant to the hemolytic algae than the blackhead seabream (Acanthopagrus schlegelii), with decreased heart rate and blood flow being observed in medaka larvae after exposure to toxic algal extracts. LC-MS/MS analysis detected a gambierone analogue called 44-methylgambierone produced by the C. tropicalis isolate. This analogue was also detected in the F. ruetzleri isolate. This study provided new information on the hemolysis associated toxicities of local toxic benthic dinoflagellates, which contributes to better understanding of their emerging threats to marine fauna and reef systems in Hong Kong.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111114DOI Listing
June 2020

Ciguatera Fish Poisoning: The Risk from an Aotearoa/New Zealand Perspective.

Toxins (Basel) 2020 01 15;12(1). Epub 2020 Jan 15.

AgResearch Limited, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New Zealand.

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http://dx.doi.org/10.3390/toxins12010050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020403PMC
January 2020

Morphology and Phylogenetics of Benthic Species (Dinophyceae) from Tropical Northwestern Australia.

Toxins (Basel) 2019 09 30;11(10). Epub 2019 Sep 30.

Climate Change Cluster, University of Technology Sydney, Ultimo, NSW 2007, Australia.

Approximately 70 species of are known, of which around 30 species are associated with benthic habitats. Some produce okadaic acid (OA), dinophysistoxin (DTX) and their derivatives, which are involved in diarrhetic shellfish poisoning. In this study, we isolated and characterized and from Broome in north Western Australia using light and scanning electron microscopy as well as molecular sequences of large subunit regions of ribosomal DNA, marking the first record of these species from Australian waters. The morphology of the motile cells of was similar to in the light microscopy, but differed by the smooth thecal surface, the pore pattern and the production of mucous stalk-like structures and a hyaline sheath around the non-motile cells. could also be differentiated from other closely related species, and , despite the similarity in thecal surface and pore pattern, by its platelet formula and morphologies. We tested the production of OA and DTXs from both species, but found that they did not produce detectable levels of these toxins in the given culturing conditions. This study aids in establishing more effective monitoring of potential harmful algal taxa in Australian waters for aquaculture and recreational purposes.
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http://dx.doi.org/10.3390/toxins11100571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833055PMC
September 2019

Improving endoscopy efficiency by reducing turnaround time between cases.

Future Healthc J 2019 Mar;6(Suppl 1):34

Gastroenterology, Homerton University Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.7861/futurehosp.6-1-s34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616686PMC
March 2019

Impact of acute handling stress, anaesthesia, and euthanasia on fish plasma biochemistry: implications for veterinary screening and metabolomic sampling.

Fish Physiol Biochem 2019 Aug 25;45(4):1485-1494. Epub 2019 Jun 25.

Cawthron Institute, Nelson, New Zealand.

Impacts of pre-sampling practices on fish plasma biochemistry may bias the outcome of a study if not considered within the general sampling strategy. Acute handling stresses can be imposed on fish during capture, and it is common practice to immobilise fish via sedation prior to obtaining blood samples for non-lethal extraction purposes, and/or to reduce stress, pain, or suffering before being euthanised. We investigated these potential influences using a Chinook salmon model (Oncorhynchus tshawytscha) by measuring levels of 119 biochemical targets comprising ions, metabolites, and enzymes in plasma. Multivariate analyses showed that 2 min of confinement with mild handling manipulation led to a significant departure from baseline metabolism, which was further exasperated during a prolonged 5-min challenge. These changes were characterised by a disruption in osmoregulation, a switch towards anaerobic metabolism, and shifts in ammonia recycling, among others. Sedation of fish with clove oil and AQUI-S® had major impacts on plasma biochemical profiles, with alterations signalling changes in glycolytic metabolism, respiratory modes, carbon flux through the TCA cycle, and lipid compartmentalisation. Sedation also enhanced levels of plasma amino acids, revealing a key difference between responses to handling stress and sedation. These results demonstrate that pre-harvest practices should be carefully managed during fish sampling for biochemical/metabolomic-based analyses, and if manipulations are essential, they should be standardised.
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http://dx.doi.org/10.1007/s10695-019-00669-8DOI Listing
August 2019

Improving safety and reducing error in endoscopy: simulation training in human factors.

Frontline Gastroenterol 2019 Apr 9;10(2):160-166. Epub 2019 Jan 9.

Department of Gastroenterology, Homerton University Hospital, London, UK.

Patient safety incidents occur throughout healthcare and early reports have exposed how deficiencies in 'human factors' have contributed to mortality in endoscopy. Recognising this, in the UK, the Joint Advisory Group for Gastrointestinal Endoscopy have implemented a number of initiatives including the 'Improving Safety and Reducing Error in Endoscopy' (ISREE) strategy. Within this, simulation training in human factors and Endoscopic Non-Technical Skills (ENTS) is being developed. Across healthcare, simulation training has been shown to improve team skills and patient outcomes. Although the literature is sparse, integrated and in situ simulation modalities have shown promise in endoscopy. Outcomes demonstrate improved individual and team performance and development of skills that aid clinical practice. Additionally, the use of simulation training to detect latent errors in the working environment is of significant value in reducing error and preventing harm. Implementation of simulation training at local and regional levels can be successfully achieved with collaboration between organisational, educational and clinical leads. Nationally, simulation strategies are a key aspect of the ISREE strategy to improve ENTS training. These may include integration of simulation into current training or development of novel simulation-based curricula. However used, it is evident that simulation training is an important tool in developing safer endoscopy.
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http://dx.doi.org/10.1136/flgastro-2018-101078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540271PMC
April 2019

Development of an LC-MS/MS method to simultaneously monitor maitotoxins and selected ciguatoxins in algal cultures and P-CTX-1B in fish.

Harmful Algae 2018 12 9;80:80-87. Epub 2018 Oct 9.

Cawthron Institute, Private Bag 2, Nelson 7010, New Zealand(1). Electronic address:

Ciguatera fish poisoning is a serious human health issue that is highly localized to tropical and sub-tropical coastal areas, affecting many of the indigenous island communities intrinsically linked to reef systems for sustenance and trade. It is caused by the consumption of reef fish contaminated with ciguatoxins and is reported as the most common cause of non-bacterial food poisoning. The causative toxins bioaccumulate up the food web, from small herbivorous fish that graze on microalgae of the genus Gambierdiscus into the higher trophic level omnivorous and carnivorous fish predating on them. The number of Gambierdiscus species being described is increasing rapidly and the role of other toxins produced by this microalgal genus in ciguatera intoxications, such as maitotoxin, remains unclear. Ciguatoxins and maitotoxin are among the most potent marine toxins known and there are currently no methods of analysis that can simultaneously monitor these toxins with a high degree of specificity. To meet this need a rapid and selective ultra-performance liquid chromatography tandem mass spectrometry method has been developed to rapidly screen Gambierdiscus cultures and environmental sample device extracts for ciguatoxins and maitotoxins. A fast sample preparation method has also been developed to allow sensitive quantification of the potent ciguatoxin fish metabolite P-CTX-1B from fish extracts, and this method has been subjected to a small validation study. Novel aspects of this approach include the use of alkaline mobile phase for chromatographic separation and specific monitoring of the various toxins. This method has good potential to help evaluate ciguatera risk associated with Gambierdiscus and related microalgal species, and to help promote method development activities for this important and analytically challenging toxin class.
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http://dx.doi.org/10.1016/j.hal.2018.09.001DOI Listing
December 2018

Preventing Post-ERCP Pancreatitis: The Role of Prophylactic Pancreatic Duct Stenting in the Rectal NSAID Era.

JOP 2017 Jul 31;18(4):316-319. Epub 2017 Jul 31.

Pancreaticobiliary Medicine Unit, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

Background: Rectal non-steroidal anti-inflammatory drug at endoscopic retrograde cholangiopancreatography is now the standard of care to reduce the risk of post-ERCP pancreatitis. Pancreatic duct stenting also reduces the risk of post- ERCP pancreatitis in high-risk patients, but failed pancreatic duct stenting carries an increased PEP rate (up to 35%).

Study Aim: To assess the impact on post-ERCP pancreatitis of successful and unsuccessful pancreatic duct stent placement in the setting of universal rectal non-steroidal anti-inflammatory drug use.

Methods: Between 2013-2015, all patients undergoing endoscopic retrograde cholangiopancreatographys in our tertiary referral centre (where rectal non-steroidal anti-inflammatory drugs are used routinely) were included. The electronic patient's records were reviewed and the following parameters were analysed: indication for pancreatic duct stenting; deployment success; and adverse events.

Results: A total of 1633 endoscopic retrograde cholangiopancreatographys were performed, and pancreatic duct stenting was attempted in 324 cases (20%), with successful placement in 307 patients (95%). Contra-indications to non-steroidal anti-inflammatory drugs were found in 106 (6.5%) patients. Prophylactic stenting failed in 12 of 213 patients; of whom one patient developed post-ERCP pancreatitis (8%). Eighteen (9%) patients with prophylactic pancreatic duct stents developed post-ERCP pancreatitis compared to 1.4% without prophylactic stents (RR 8.4, p=0.04).

Conclusion: A lack of difference in post-ERCP pancreatitis in those who underwent successful, and unsuccessful, pancreatic duct stent placement may reflect the protective effect of non-steroidal anti-inflammatory drugs. This data adds to evidence suggesting that pancreatic duct stenting may be less important, even in high-risk patients, with the widespread use of non-steroidal anti-inflammatory drugs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933872PMC
July 2017

Phylogeny, morphology and toxicity of benthic dinoflagellates of the genus Fukuyoa (Goniodomataceae, Dinophyceae) from a subtropical reef ecosystem in the South China Sea.

Harmful Algae 2018 04 17;74:78-97. Epub 2018 Apr 17.

State Key Laboratory in Marine Pollution, City University of Hong Kong, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China. Electronic address:

Species of Fukuyoa, recently revised from the globular Gambierdiscus, are toxic benthic dinoflagellates associated with ciguatera. In this study, a total of ten strains of Fukuyoa collected from Hong Kong waters were characterized using morphological and phylogenetic analyses. Results from both analyses showed that one of the strains is a putative new species, namely Fukuyoa sp. HK Type 1 (plate formula Po, 3', 7″, 6c, 7s, 5‴, 1p and 2'‴ with a distinctive small and narrow cell shape, narrow Po plate, high Po pore density, large and broad Plate 1' but small and round Po pore size, small and narrow Plate 2', long and narrow Plates 2'‴ and 1p), and the others were F. ruetzleri. This is the first report of these two species of Fukuyoa in the South China Sea and Asia-Pacific region. Phylogenies on 18S, 28S D1/D3 and D8/D10 ribosomal DNA sequences strongly support that Fukuyoa sp. HK Type 1 is currently the most divergent species in the genus Fukuyoa. The diagrammatic plots on the p-distance matrices of 18S, 28S D1/D3 and D8/D10 and ITS regions resolved that the species of Fukuyoa were separated into three main groups, i.e., Fukuyoa sp. HK Type 1, F. paulensis and a group consisting of F. ruetzleri, F. yasumotoi and F. cf. yasumotoi, while Fukuyoa sp. HK Type 1 was always the most distant from the other two groups. Additionally, the pairwise p-distance values calculated based on the ITS region have always been the highest for pairs between Fukuyoa sp. HK Type 1 and other Fukuyoa species, ranging from 0.142 to 0.150. Our molecular results suggested that Fukuyoa sp. HK Type 1 is a putative new species. Both morphological and molecular data of more strains from different localities should be, however, collected to address its intraspecific variability and further evaluate its taxonomic status. A bioassay analysis demonstrated that algal lysates extracted from F. ruetzleri and Fukuyoa sp. HK Type 1 were lethal to brine shrimp larvae, indicating that both species were toxic. Bulk cultures were tested for Pacific ciguatoxins (P-CTXs) and maitotoxins (MTXs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). All isolates of Fukuyoa produced neither P-CTXs nor MTX-1, but isolates of F. ruetzleri produced a compound putatively assigned as MTX-3. This study has updated the current biodiversity and distribution of the toxic benthic dinoflagellates Fukuyoa, and thus contributes to the understanding of their emerging threats to the sub-tropical reef systems locally and regionally.
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http://dx.doi.org/10.1016/j.hal.2018.03.003DOI Listing
April 2018

Detection of Paralytic Shellfish Toxins in Mussels and Oysters Using the Qualitative Neogen Lateral-Flow Immunoassay: An Interlaboratory Study.

J AOAC Int 2018 Mar 30;101(2):468-479. Epub 2017 Aug 30.

South Australian Research and Development Institute, 2b Hartley Grv., Urrbrae, SA 5064, Australia.

Paralytic shellfish toxins (PSTs) in bivalve molluscs represent a public health risk and are controlled via compliance with a regulatory limit of 0.8 mg saxitoxin (STX)⋅2HCl equivalents per kilogram of shellfish meat (eq/kg). Shellfish industries would benefit from the use of rapid immunological screening tests for PSTs to be used for regulation, but to date none have been fully validated. An interlaboratory study involving 16 laboratories was performed to determine the suitability of the Neogen test to detect PSTs in mussels and oysters. Participants performed the standard protocol recommended by the manufacturer and a modified protocol with a conversion step to improve detection of gonyautoxin 1&4. The statistical analysis showed that the protocols had good homogeneity across all laboratories, with satisfactory repeatability, laboratory, and reproducibility variation near the regulatory level. The mean probability of detection (POD) at 0.8 mg STX⋅2HCl eq/kg using the standard protocol in mussels and oysters was 0.966 and 0.997, respectively, and 0.968 and 0.966 using the modified protocol. The estimated LOD in mussels was 0.316 mg STX⋅2HCl eq/kg with the standard and 0.682 mg STX⋅2HCl eq/kg with the modified protocol, and 0.710 and 0.734 mg STX⋅2HCl eq/kg for oysters, respectively. The Neogen test may be acceptable for regulatory purposes for oysters in accordance with European Commission directives in which the standard protocol provides, at the regulatory level, a probability of a negative response of 0.033 on 95% of occasions. Its use for mussels is less consistent at the regulatory level due to the wide prediction interval around the POD.
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http://dx.doi.org/10.5740/jaoacint.17-0221DOI Listing
March 2018

The role of multidisciplinary meetings for benign pancreatobiliary diseases: a tertiary centre experience.

Frontline Gastroenterol 2017 Jul 5;8(3):210-213. Epub 2016 Sep 5.

Department of Pancreato-Biliary Diseases, University College London Hospital, London, UK.

Multidisciplinary meetings are central to the management of chronic and complex diseases and they have become widely established across the modern healthcare. Patients with pancreatobiliary diseases can often present with complex clinical dilemmas, which fall out with the scope of current guidelines. Therefore, these patients require a personalised management approach discussed in a multidisciplinary meeting.
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http://dx.doi.org/10.1136/flgastro-2016-100717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558274PMC
July 2017

The Epiphytic Genus Gambierdiscus (Dinophyceae) in the Kermadec Islands and Zealandia Regions of the Southwestern Pacific and the Associated Risk of Ciguatera Fish Poisoning.

Mar Drugs 2017 Jul 11;15(7). Epub 2017 Jul 11.

AgResearch, Ruakura Research Centre, 10 Bisley Road, Private Bag 3240, Hamilton 3214, New Zealand.

Species in the genus produce ciguatoxins (CTXs) and/or maitotoxins (MTXs), which may cause ciguatera fish poisoning (CFP) in humans if contaminated fish are consumed. Species of have previously been isolated from macroalgae at Rangitahua (Raoul Island and North Meyer Islands, northern Kermadec Islands), and the opportunity was taken to sample for at the more southerly Macauley Island during an expedition in 2016. cells were isolated, cultured, and DNA extracted and sequenced to determine the species present. Bulk cultures were tested for CTXs and MTXs by liquid chromatography-mass spectrometry (LC-MS/MS). The species isolated were , which produced MTX-1 (ranging from 3 to 36 pg/cell), and , which produced neither MTX-1 nor, unusually, any known CTXs. Isolates of both species produced putative MTX-3. The risk of fish, particularly herbivorous fish, causing CFP in the Zealandia and Kermadec Islands region is real, although in mainland New Zealand the risk is currently low. Both and have been recorded in the sub-tropical northern region of New Zealand, and so the risk may increase with warming seas and shift in the distribution of species.
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http://dx.doi.org/10.3390/md15070219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532661PMC
July 2017

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration.

Mar Drugs 2017 Jun 30;15(7). Epub 2017 Jun 30.

Cawthron Institute, Halifax Street Campus, Private Bag 2, Nelson 7042, New Zealand.

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the species, and one species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of contained neither CTXs nor MTXs, while 15 other isolates (including , , , and ) contained only MTX-1 and/or MTX-3. An isolate of contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of was highly toxic by both routes of administration.
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http://dx.doi.org/10.3390/md15070208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532650PMC
June 2017

A new species of Gambierdiscus (Dinophyceae) from the south-west Pacific: Gambierdiscus honu sp. nov.

Harmful Algae 2017 05 2;65:61-70. Epub 2017 May 2.

Plant Functional Biology and Climate Change Cluster, University of Technology Sydney, PO Box 123, Broadway, New South Wales 2007, Australia; Sydney Institute of Marine Sciences, Chowder Bay Rd, Mosman 2088, New South Wales, Australia.

Two isolates of a new tropical, epiphytic dinoflagellate species, Gambierdiscus honu sp. nov., were obtained from macroalgae sampled in Rarotonga, Cook Islands, and from North Meyer Island, Kermadec Islands. Gambierdiscus honu sp. nov. had the common Gambierdiscus Kofoidian plate formula: Po, 3', 6″, 6C?, 6 or 7S, 5‴, 1p and 2⁗. The characteristic morphological features of this species were its relatively small short dorsoventral length and width and the shape of individual plates, in particular the combination of the hatchet-shaped 2' and pentagonal 3' plates and the length to width ratio of the antapical 1p plate. The combination of these characteristics plus the smooth thecal surface and equal sized 1⁗ and 2⁗ plates differentiated this species from other Gambierdiscus species. The phylogenetic analyses supported the unique description. Both isolates of G. honu produced the putative maitotoxin (MTX)-3 analogue, but neither produced ciguatoxin (CTX) or MTX. Extracts of G. honu were shown to be highly toxic to mice by intraperitoneal injection (0.2mg/kg), although less toxic by gavage. It is possible that toxins other than putative MTX-3 are produced.
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http://dx.doi.org/10.1016/j.hal.2017.04.010DOI Listing
May 2017

Pancreatoscopy-Directed Electrohydraulic Lithotripsy for Pancreatic Ductal Stones in Painful Chronic Pancreatitis Using SpyGlass.

Pancreas 2017 04;46(4):528-530

From the *Pancreatobiliary Medicine Unit and †Radiology Department, University College London Hospitals, London, United Kingdom.

Objective: Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy, or endoscopic approaches. Here, we report our experience of pancreatoscopy + electrohydraulic lithotripsy (EHL) for pancreatic duct (PD) stones using SpyGlass.

Methods: We retrospectively audited the use of SpyGlass (Legacy and DS) + EHL. Indication, procedural details, and clinical outcomes were assessed.

Results: A total of 118 SpyGlass + EHL procedures for stones were performed, of which 8 (7%) for pancreatic stones, in 6 patients (3 female; mean [standard deviation] age, 45 [7] years). All patients had painful chronic pancreatitis, with radiological evidence of a dilated PD, and main duct stone disease. Surgical options had been considered in all cases. Stone fragmentation and PD decompression were achieved in 83% (n = 5) without complications. Two patients required 2 EHL procedures to achieve clearance. In 1 patient with failed clearance, pancreatoscopy revealed a stone in the adjacent parenchyma and not in PD. All patients with successful EHL had pain relief/marked improvement at clinical review (mean [standard deviation] follow-up, 2.7 [1.1] years).

Conclusions: Pancreatoscopy + EHL may have a valuable role in treating obstructing PD stones, possibly avoiding the need for surgery in some patients.
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http://dx.doi.org/10.1097/MPA.0000000000000790DOI Listing
April 2017

Endoscopic versus percutaneous drainage of symptomatic pancreatic fluid collections: a 14-year experience from a tertiary hepatobiliary centre.

Surg Endosc 2016 09 16;30(9):3730-40. Epub 2015 Dec 16.

Institute for Liver and Digestive Health, Royal Free Hospital, University College London, Pond St, London, NW3 2PF, UK.

Introduction: Endoscopic transmural drainage (ED) or percutaneous drainage (PD) has mostly replaced surgery for the initial management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare outcomes for patients undergoing ED or PD of symptomatic PFCs.

Methods: Between January 2000 and December 2013, all patients who required PD or ED of a PFC were included. Rates of treatment success, length of hospital stay, adverse events, re-interventions and length of follow-up were recorded retrospectively in all cases.

Results: In total, 164 patients were included in the study; 109 patients underwent ED; and 55 had PD alone. During the 14-year study period, the incidence of ED increased and PD fell. In the 109 patients who were managed by ED, treatment success was considerably higher than in those managed by PD (70 vs. 31 %). Rates of procedural adverse events were higher in the ED cohort compared to the PD group (10 vs. 1 %), but patients managed by ED required fewer interventions (median of 1.8 vs. 3.3) had lower rates of residual collections (21 vs. 67 %) and need for surgical intervention (4 vs. 11 %). In the ED group, treatment success was similar for walled-off pancreatic necrosis (WOPN) and pseudocysts (67 vs. 72 %, P = 0.77). There were no procedure-related deaths.

Conclusion: Compared with PD, ED of symptomatic PFCs was associated with higher rates of treatment success, lower rates of re-intervention, including surgery and shorter lengths of hospital stay. Outcomes in WOPN were comparable to those in patients with pseudocysts.
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http://dx.doi.org/10.1007/s00464-015-4668-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992018PMC
September 2016

Cryoablation versus radiofrequency ablation for treatment of atrioventricular nodal reentrant tachycardia: cryoablation with 6-mm-tip catheters is still less effective than radiofrequency ablation.

Heart Rhythm 2010 Mar 2;7(3):340-3. Epub 2009 Dec 2.

Heart Rhythm Service, St. Bartholomew's Hospital, London, UK.

Background: The treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT) is catheter ablation of the atrioventricular nodal slow pathway.

Objective: The purpose of this study was to ascertain whether cryoablation (Cryo) with 6-mm-tip catheters is as effective as radiofrequency ablation (RF).

Methods: Patients who had catheter ablation for AVNRT between 2005 and 2008 were identified. The main outcome measure was overall success without the use of an alternative energy source and no recurrence.

Results: Two hundred eighty-eight procedures in 272 patients were identified; 184 were female (68%), and the mean age was 53 +/- 14 (17-88) years. There were 123 Cryo and 149 RF procedures. Cryo had a lower overall success rate (83% vs. 93%; P = .02). Mean procedure times were similar in both groups (90 minutes; P = .5). Fluoroscopy time was longer with Cryo: 16 (7-48) versus 14 (5-50) minutes (P = .04). Only one case of atrioventricular block was observed in the RF group (0.7%). Cryo was more expensive than RF ( pounds sterling 3141 vs. pounds sterling 2153).

Conclusion: Even when delivering multiple lesions with 6-mm-tip catheters, Cryo is less effective than RF. RF is recommended as a first-line treatment, although the only major complication occurred in the RF group.
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http://dx.doi.org/10.1016/j.hrthm.2009.11.029DOI Listing
March 2010
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