The Human Tissue-Biomaterial Interface : A Role for PPARγ-Dependent Glucocorticoid Receptor Activation in Regulating the CD163(+) M2 Macrophage Phenotype

In vivo studies of implanted acellular biological scaffolds in experimental animals have shown constructive remodeling mediated by anti-inflammatory macrophages. Little is known about the human macrophage response to such biomaterials, or the nature of the signaling mechanisms that govern the macrophage phenotype in this environment. The cellular events at the interface of a tissue and implanted decellularized biomaterial were examined by establishing a novel ex vivo tissue culture model in which surgically excised human urinary tract tissue was combined with porcine acellular bladder matrix (PABM). Evaluation of the tissue-biomaterial interface showed a time-dependent infiltration of the biomaterial by CD68(+) CD80(-) macrophages. The migration of CD68(+) cells from the tissue to the interface was accompanied by maturation to a CD163(hi) phenotype, suggesting that factor(s) associated with the biomaterial or the wound edge was/were responsible for the active recruitment and polarization of local macrophages. Glucocorticoid receptor (GR) and peroxisome proliferator activated receptor gamma (PPARγ) signaling was investigated as candidate pathways for integrating inflammatory responses; both showed intense nuclear labeling in interface macrophages. GR and PPARγ activation polarized peripheral blood-derived macrophages from a default M1 (CD80(+)) toward an M2 (CD163(+)) phenotype, but PPARγ signaling predominated, as its antagonism blocked any GR-mediated effect. Seeding on PABM was effective at polarizing peripheral blood-derived macrophages from a default CD80(+) phenotype on glass to a CD80(-) phenotype, with intense nuclear localization of PPARγ. These results endorse in vivo observations that the infiltration of decellularized biological scaffolds, exemplified here by PABM, is pioneered by macrophages. Thus, it appears that natural factors present in PABM are involved in the active recruitment and polarization of macrophages to a CD163(+) phenotype, with activation of PPARγ identified as the candidate pathway. The harnessing of these natural matrix-associated factors may be useful in enhancing the integration of synthetic and other natural biomaterials by polarizing macrophage activation toward an M2 regulatory phenotype

Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma&ndash;optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.<br /

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

Giant mediastinal mature teratoma with increased exocrine pancreatic activity presenting in a young woman: a case report

Abstract Introduction Mediastinal mature teratoma is a benign, slow-growing tumor typically affecting 20- to 40-year-old adults. Fluid examination from the cystic masses rarely shows enzymatic activity as we describe in this report. Case presentation We report a case of a giant mediastinal germ cell tumor (measuring 15 cm × 14 cm × 8 cm) detected in a 35-year-old Caucasian woman. Microscopic examination showed that the lesion resembled a mature cystic teratoma with areas of pancreatic tissue with mature ductal and acinar structures intermixed with islets of Langerhans. Fluid from the cysts in the mass was examined after removal showed amylase activity of 599 U/l despite normal serum levels. The post-operative period was free of complications, and the patient was discharged on post-operative day 10. Conclusion Complete surgical removal is the treatment of choice for mature cystic teratomas, with optimal results and acceptable surgical risk. Exocrine pancreatic function may be an aid to pre-operative or intra-operative diagnosis; however, these findings have no impact on survival or the therapeutic pathway.</p

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

Academic self-concept, gender and single-sex schooling

This paper assesses gender differences in academic self-concept for a cohort of children born in 1958 (the National Child Development Study). We address the question of whether attending single-sex or co-educational schools affected students’ perceptions of their own academic abilities (academic self-concept). Academic selfconcept was found to be highly gendered, even controlling for prior test scores. Boys had higher self-concepts in maths and science, and girls in English. Single-sex schooling reduced the gender gap in self-concept, while selective schooling was linked to lower academic self-concept overall

Animal welfare impacts of badger culling operations

We are writing to express our extreme concern following recent media coverage1, 2 relating to the methodology being used by contractors to kill badgers under licence, as part of the government’s policy to control bovine TB in cattle. The coverage relates to the shooting of badgers that have been captured in live traps. Covert video footage (https://bit.ly/2Eud1iR ) from Cumbria shows a trapped badger being shot with a firearm at close range, following which it appears to take close to a minute to stop moving. The contractor clearly observes the animal during this time but makes no attempt to expedite the death of the badger and prevent further suffering, as required by the current Natural England best practice guide which states: ‘Immediately after shooting, the animal should be checked to ensure it is dead, and if there is any doubt, a second shot must be taken as soon as possible.’3 The conversation between the contractor and his companion also suggests they were considering moving the badger to another site before finally bagging the carcase, again breaching the best practice guide. While the footage only relates to the experience of a single badger, and while the degree to which the badger was conscious in the period immediately following the shot is unclear, we can by no means be certain that the badger did not suffer. It also raises serious questions about the training, competence and behaviour of contractors, in relation to both badger welfare, and biosecurity. This adds to existing concerns relating to the humaneness of ‘controlled shooting’ (targeting free-roaming badgers with rifles), which continues to be a permitted method under culling licences, in spite of the reservations expressed by both the government-commissioned Independent Expert Panel in its 2014 report,4 and the BVA, which concluded in 2015 that it ‘can no longer support the continued use of controlled shooting as part of the badger control policy’.5 (However, it has since continued to support the issuing of licences which permit the method). The BVA has consistently indicated its support for what it calls the ‘tried and tested’ method of trapping and shooting, but has thus far failed to provide comprehensive and robust evidence for the humaneness of this method. Figure1 Download figure Open in new tab Download powerpoint Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness During 2017, almost 20,000 badgers were killed under licence across 19 cull zones, around 60 per cent of which were killed by controlled shooting, the remainder being trapped and shot.6 Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness. No information has been provided on the extent to which trapping and shooting activities were monitored. This raises serious concerns about the extent of suffering that might be experienced by very large numbers of animals, for which contractors are not being held to account. If contractors reach their maximum culling targets set by Natural England for 2018, as many as 41,000 additional badgers could be killed.7 The extent to which these animals will suffer is once again being left in the hands of contractors, with woefully inadequate oversight, and in the face of anecdotal evidence of breaches of best practice guidance. This situation is clearly unacceptable from an animal welfare perspective and it is our view that by endorsing the policy, the BVA is contradicting the principles contained within its own animal welfare strategy.8 We therefore urge the BVA to withdraw its support for any further licensed badger culling, and the RCVS to make it clear that any veterinarian who provides support for culling activities that result in unnecessary and avoidable animal suffering could face disciplinary proceedings. The veterinary profession has no business supporting this licensed mass killing with all its inherent negative welfare and biosecurity implications, and for which the disease control benefits are, at best, extremely uncertain. We believe the continued support for the culls by veterinary bodies in the face of poor evidence for its efficacy damages the credibility of the profession, and that same support in the face of potential animal suffering on a large scale undermines its reputation. We stand ready to discuss these issues in more detail