Biosecurity and the ornamental fish trade: A stakeholder perspective in England

The freshwater and marine ornamental fish industry is a primary route of hazard introduction and emergence, including aquatic animal diseases and non-native species. Prevention measures are key to reducing the risk of hazard incursion and establishment, but there is currently little understanding of the biosecurity practices and hazard responses implemented at post-border stages of the ornamental fish supply chain. This study addresses this knowledge gap, using questionnaires to collate information on actual biosecurity behaviours and hazard responses practised by ornamental fish retailers and hobbyist communities in England. Actual behaviours varied considerably within retailers and hobbyists, suggesting that reliance on preventative practices by individuals in the post-border stages of the ornamental fish supply chain is likely to be ineffective in minimizing the risk of hazard incursion and establishment. Resources should be allocated towards improving and enforcing robust pre- and at-border control measures, such as risk-based surveillance of ornamental fish imports at border controls. In addition, these findings should be used to implement targeted awareness-raising campaigns and help create directed training on biosecurity practices for individuals involved in the post-border stages of the ornamental supply chain

Monitoring quality of care in hepatocellular carcinoma: A modified delphi consensus

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival

Diabetes and hemochromatosis

Hereditary hemochromatosis is due, in most cases, to a common genetic mutation in the HFE gene which leads to the C282Y substitution, which in turn can result in end organ damage from iron overload. The major manifestations in advanced disease are skin pigmentation, diabetes ('bronzed diabetes') and cirrhosis of the liver. When present, these features are associated with a reduced life expectancy and the possibility of hepatocellular carcinoma. It may be considered as an endocrine disorder where, instead of insulin, the peptide hepcidin is deficient, leading to an unregulated increase in iron absorption from the intestine. When present, diabetes is due to a defect in beta cell function resulting from iron deposition in these cells. Increased insulin resistance may also be present in cases of advanced liver disease. Fortunately, patients are now more frequently being diagnosed at an earlier stage and have a good prognosis when appropriate treatment for the iron loading is instituted. In this situation, diabetes is less frequently seen. This review summarizes current knowledge about the pathogenesis of hereditary hemochromatosis, its association with diabetes mellitus and the management of these conditions

Allergy controls the population density of Necator americanus in the small intestine

Background & Aims: Nearly 700 million people remain infected with hookworms. Although allergy is intuitively linked to immunity against helminths, few positive examples have been characterized. Larval migration through the lungs has been considered the likely interface at which hookworm attrition occurs. As part of a study evaluating a potential role for hookworms in the modulation of human autoimmunity, we examined parasite migration and intestinal colonization. Methods: Capsule and conventional endoscopies supplemented the evaluation of healthy volunteers and Crohn’s disease patients recently inoculated with larvae of the human hookworm Necator americanus. Two healthy volunteers with a previously established and stable hookworm infection were inoculated with 50 larvae and had serial capsule endoscopies performed. Results: Eosinophilic enteritis developed in all subjects after the initial inoculation. Newly inoculated larvae in the 2 subjects with an established infection reliably reached the intestine within 4 weeks. Thereafter, the colony diminished to the host’s constitutive status quo because mostly immature worms failed to attach. The intensity of the eosinophilic response correlated negatively with the time available for hookworms to feed and positively with hookworm attrition. Conclusions: Necator larval migration to the intestine is uncontested. We propose that allergic inflammation purposefully degrades the hookworm’s bite, causing premature detachment, restricted feeding, and expulsion. This novel biological dynamic suggests a new paradigm of hookworm resistance

Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

AIM: To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis

Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis

Background & AimsFerritin is purported to have proinflammatory and profibrogenic effects on hepatic stellate cells. Thus, rather than acting as a passive indicator of hepatic iron concentration (HIC) in haemochromatosis, ferritin may directly influence fibrosis. This study evaluated whether serum ferritin is a better predictor of hepatic fibrosis compared to variables previously associated with increased fibrosis risk in haemochromatosis

Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed via a non-CB(1)/CB(2) G(i/o) linked receptor

1. Noladin ether has recently been reported to be an endocannabinoid, with selectivity for the cannabinoid (CB) CB(1) receptor. In the present study, we investigated the effects of noladin ether in the rat isolated mesenteric arterial bed, cultured dorsal root ganglia (DRG) cells and human vanilloid (TRPV1)-receptor-expressing HEK293 cells (TRPV1-HEK293 cells). 2. Electrical field stimulation of the mesenteric bed evoked frequency-dependent vasorelaxation due to the action of calcitonin gene-related peptide (CGRP) released from sensory nerves. Noladin ether (0.1–3 μM) attenuated sensory neurogenic relaxation in a concentration-dependent manner. Noladin ether (1 μM) reduced vasorelaxation at a submaximal frequency (8 Hz), from 57.3±6.8 to 23.3±3.8% (P<0.05, n=4). 3. The inhibitory effects of noladin ether were unaffected by the CB(1) antagonists SR141716A and LY320135, and the CB(2) antagonist SR144528 (1 μM). 4. Noladin ether had no effect on vasorelaxation elicited by exogenous CGRP or capsaicin. These data suggest that noladin ether is acting at a prejunctional site and no interaction with TRPV1 is involved. 5. In mesenteric beds from pertussis toxin (PTX)-pretreated rats, the inhibitory actions of noladin ether on sensory neurotransmission were abolished, indicating the involvement of G(i/o) protein-coupled receptors. 6. Noladin ether evoked a concentration-dependent increase in intracellular Ca(2+) concentration in TRPV1-HEK293 cells at 10 μM (36.5±3.2% of maximal capsaicin-induced response), but it was a less potent agonist than both capsaicin and anandamide and at 1 μM it was essentially inactive. Noladin ether (1 μM) had no effect on capsaicin-evoked Ca(2+) responses in DRG cells, and produced no response alone, indicating it neither modulates nor acts directly on TRPV1 receptors. 7. These data demonstrate that noladin ether attenuates sensory neurotransmission in rat mesenteric arteries via a non-CB(1) non-CB(2) PTX-sensitive prejunctional site, independently of TRPV1 receptors