Fluorodeoxyglucose positron emission tomography in the evaluation of germ cell tumours at relapse

Differentiation of active disease from fibrosis/mature teratoma in patients with residual masses or identifying of sites of recurrence in patients with raised markers following treatment of their testicular cancer remains a problem.18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management in these patients. We performed a retrospective study of the use of FDG-PET in detecting residual/recurrent testicular carcinoma in 55 patients (seventy FDG-PET scans). Forty-seven scans were for the assessment of residual masses (18 had raised markers) and 23 scans were for the investigation of raised markers in the presence of normal CT scans. True positive results were based on positive histology or clinical follow-up. FDG-PET had a positive predictive value (PPV) of 96% and a negative predictive value (NPV) of 90% in patients with residual masses. This PPV was equivalent to that of markers (94%) but FDG-PET had the advantage of identifying the site of that recurrence. The NPV was higher than that of markers. In patients with raised markers alone the PPV of FDG-PET was 92% but the NPV was only 50%. However, subsequent FDG-PET imaging was frequently the first imaging modality to identify the site of disease. FDG-PET effected a management change in 57% of cases. FDG-PET scanning detected viable tumour in residual masses and identified sites of disease in suspected recurrence. © 2000 Cancer Research Campaig

The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis

DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect of M. bovis infection on the bAM DNA methylome. The methylomes of bAM infected with M. bovis were compared to those of non-infected bAM 24 hours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33-66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

“Ghosts from the past”: The re-emergence of internalised religious stigma following diagnosis of HIV among Northern Irish gay men

This paper explores how previous exposure to religious homo-negativity features in the sense making process following HIV diagnosis in a homogenous sample of six gay men living in Northern Ireland. Interpretive Phenomenological Analysis was used to identify two key overarching themes: ‘Negotiating authenticity in unsafe space’ which relates to the experience of negotiating same sex attraction within religious environments and ‘Re-emergence of religious shame in diagnosis’ which relates to the way in which the men made sense of diagnosis from the position of having been exposed to religious homo-negativity earlier in their lives. Findings demonstrate how the men negotiated their sexual orientation within religious contexts and how a reconstruction of God was necessary to preserve an authentic sense of self. Despite reaching reconciliation, HIV was initially appraised within a retributive religious framework that served to temporarily reinforce previously learned shame-based models of understanding this aspect of the self

Systematic review of pre-operative exercise in colorectal cancer patients

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality

Pavlovian Reward Prediction and Receipt in Schizophrenia: Relationship to Anhedonia

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a Pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity

Replacement of soya bean meal with peas and faba beans in growing/finishing pig diets: effect on performance, carcass composition and nutrient excretion

There is now an increasing debate about the viability of using temperate-grown legumes in pig diets as a potential replacement for imported soya bean meal (SBM) and this is due to food security, sustainability and environmental concerns. Two trials were designed to examine nitrogen (N) retention, growth performance and carcass quality of grower and finisher pigs when fed nutritionally balanced SBM-free diets formulated to contain peas or faba beans at 300 g/kg, compared to an SBM-containing, pulse-free control diet. Trial 1 evaluated N digestibility/retention in four iso-energetic diets, comparing the SBM control with one diet formulated with peas and two with faba bean cultivars; a tannin-containing and a tannin-free variety. This trial employed a four by four Latin Square design with four male pigs housed in metabolism crates, fed twice daily at 0.9 of assumed ad libitum intake over four time periods during grower (30–55 kg) and finisher (55–95 kg) phases. Quantitative faecal and urine collection allowed determination of N coefficient of total tract apparent digestibility, coefficient of apparent metabolisability, and N balance. Results revealed that dietary treatment did not affect these N parameters (P > 0.05) during either the grower or finisher phase. Trial 2 evaluated growth performance (feed intake, daily live weight gain and feed conversion ratio) and carcass quality parameters. Five diets (based on SBM, peas and one of three faba bean cultivars) balanced for standard ileal digestible amino acids and net energy were each fed to eight replicates of individually housed entire male pigs over the same growth phases as Trial 1. The inclusion of three faba bean varieties allowed comparison of animal responses between tannin/tannin-free and spring vs. winter bean cultivars. At ∼95 kg, pigs were slaughtered and a comprehensive range of carcass measurements undertaken. Samples of shoulder backfat were also taken at slaughter to determine skatole and indole concentrations. As with N balance, feeding treatment did not affect performance data. Carcass parameters revealed pigs fed with the pea-based diet had a greater dressing percentage than those animals on faba bean-based diets. Pigs fed with the SBM or pea-based diets also had greater lean meat percentages than those on faba-bean diets. Mean skatole concentrations for all pigs were below the accepted maximum threshold level of 0.2 μg/g. In conclusion, it is suggested that peas and faba beans can be successfully fed in balanced pig diets throughout the grower/finisher periods as alternatives to SBM

Professionalization of a nonstate actor

Can nonstate militants professionalize? That is the core question of this piece. Discussions of professionalism have spread to the state military from civilian professions such as education, medicine, and law. This piece examines whether nonstate actors exhibit the same fundamental processes found within these state-based organizations. These fundamentals are the creation of a recognized internal ethos, which acts as a collective standard for those involved. A commitment to expertise and the punishment of those who do not reach these collective expectations reinforce this ethos. To answer this question, this piece examines the development of the Provisional Irish Republican Army (PIRA) during the Troubles. It highlights consistencies and inconsistencies with traditional forces and argues that groups like the PIRA can professionalize and increase their effectiveness in doing so. This widens the field of professionalism studies and provides an additional lens through which to examine nonstate groups

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli