Defining Biochemical Cure After Low Dose Rate Prostate Brachytherapy: External Validation of 4-year Prostate-specific Antigen Nadir as a Predictor of 10- and 15-year Disease-free Survival.

AIMS: To externally validate a proposed biochemical definition of cure following low dose rate (LDR) brachytherapy for prostate cancer - 4-year post-implant prostate-specific antigen (PSA) ≤0.2 ng/ml - in a UK population, and report the long-term (10- and 15-year) outcomes for patients stratified by National Comprehensive Cancer Network (NCCN) risk groups, through analysis of a large, prospectively collected, single-centre database. MATERIALS AND METHODS: All patients treated with LDR brachytherapy for prostate cancer at a single UK centre between 2001 and November 2020 (n = 1142) were eligible; 632 patients met the inclusion criteria for the analysis. The primary end point was disease-free survival (DFS), defined as freedom from clinical, radiological or PSA progression requiring androgen deprivation therapy. Four-year PSA was categorised as ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml. Kaplan-Meier analysis to 15 years was undertaken for each group, and sensitivity and specificity of 4-year PSA as a surrogate for long-term cure were calculated. Kaplan-Meier analysis to 15 years was repeated, stratifying patients by NCCN risk groups. RESULTS: The median cohort age was 63 years; the median follow-up was 9.1 years (range 3.5-18.7). In total, 248 patients were available for analysis at year 10, 46 at year 15. Sixty-four patients (10.1%) relapsed during the study period. The 10-year DFS for 4-year PSA categories ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml (95% confidence intervals) were 97.5% (95.4-99.6), 89.0% (82.4-96.1), 81.5% (70.5-94.2) and 41.8% (29.7-58.9), respectively. The 10-year DFS results for NCCN low, favourable-intermediate and unfavourable-intermediate risk disease were 93.1% (89.6-96.7), 92.1% (87.6-96.9) and 75.9% (67.8-84.9), respectively. CONCLUSIONS: Patients with 4-year PSA ≤0.2 ng/ml may be considered cured, and could be discharged to general practitioner follow-up. LDR brachytherapy is an excellent treatment option for patients with low and favourable-intermediate risk prostate cancer, but those with unfavourable-intermediate risk disease should be considered for treatment intensification strategies.

Soil microbial community responses to contamination with silver, aluminium oxide and silicon dioxide nanoparticles.

Soil microorganisms are key contributors to nutrient cycling and are essential for the maintenance of healthy soils and sustainable agriculture. Although the antimicrobial effects of a broad range of nanoparticulate substances have been characterised in vitro, little is known about the impact of these compounds on microbial communities in environments such as soil. In this study, the effect of three widely used nanoparticulates (silver, silicon dioxide and aluminium oxide) on bacterial and fungal communities in an agricultural pastureland soil was examined in a microcosm-based experiment using a combination of enzyme analysis, molecular fingerprinting and amplicon sequencing. A relatively low concentration of silver nanoparticles (AgNPs) significantly reduced total soil dehydrogenase and urease activity, while Al2O3 and SiO2 nanoparticles had no effect. Amplicon sequencing revealed substantial shifts in bacterial community composition in soils amended with AgNPs, with significant decreases in the relative abundance of Acidobacteria and Verrucomicrobia and an increase in Proteobacteria. In particular, the relative abundance of the Proteobacterial genus Dyella significantly increased in AgNP amended soil. The effects of Al2O3 and SiO2 NPs on bacterial community composition were less pronounced. AgNPs significantly reduced bacterial and archaeal amoA gene abundance in soil, with the archaea more susceptible than bacteria. AgNPs also significantly impacted soil fungal community structure, while Al2O3 and SiO2 NPs had no effect. Several fungal ribotypes increased in soil amended with AgNPs, compared to control soil. This study highlights the need to consider the effects of individual nanoparticles on soil microbial communities when assessing their environmental impact.

Responses of anaerobic rumen fungal diversity (phylum Neocallimastigomycota) to changes in bovine diet.

AIMS: Anaerobic rumen fungi (Neocallimastigales) play important roles in the breakdown of complex, cellulose-rich material. Subsequent decomposition products are utilized by other microbes, including methanogens. The aim of this study was to determine the effects of dietary changes on anaerobic rumen fungi diversity. METHODS AND RESULTS: Altered diets through increasing concentrate/forage (50 : 50 vs 90 : 10) ratios and/or the addition of 6% soya oil were offered to steers and the Neocallimastigales community was assessed by PCR-based fingerprinting with specific primers within the barcode region. Both a decrease in fibre content and the addition of 6% soya oil affected Neocallimastigales diversity within solid and liquid rumen phases. The addition of 6% soya oil decreased species richness. Assemblages were strongly affected by the addition of 6% soya oil, whereas unexpectedly, the fibre decrease had less effect. Differences in volatile fatty acid contents (acetate, propionate and butyrate) were significantly associated with changes in Neocallimastigales assemblages between the treatments. CONCLUSIONS: Diet clearly influences Neocallimastigales assemblages. The data are interpreted in terms of interactions with other microbial groups involved in fermentation processes within the rumen. SIGNIFICANCE AND IMPACT OF THE STUDY: Knowledge on the influence of diet on anaerobic fungi is necessary to understand changes in microbial processes occurring within the rumen as this may impact on other rumen processes such as methane production.

The effect of dietary concentrate and soya oil inclusion on microbial diversity in the rumen of cattle.

AIMS: Methane emissions from ruminants are a significant contributor to global greenhouse gas production. The aim of this study was to examine the effect of diet on microbial communities in the rumen of steers. METHODS AND RESULTS: The effects of dietary alteration (50 : 50 vs 90 : 10 concentrate-forage ratio, and inclusion of soya oil) on methanogenic and bacterial communities in the rumen of steers were examined using molecular fingerprinting techniques (T-RFLP and automated ribosomal intergenic spacer analysis) and real-time PCR. Bacterial diversity was greatly affected by diet, whereas methanogen diversity was not. However, methanogen abundance was significantly reduced (P = 0.009) in high concentrate-forage diets and in the presence of soya oil (6%). In a parallel study, reduced methane emissions were observed with these diets. CONCLUSIONS: The greater effect of dietary alteration on bacterial community in the rumen compared with the methanogen community may reflect the impact of substrate availability on the rumen bacterial community. This resulted in altered rumen volatile fatty acid profiles and had a downstream effect on methanogen abundance, but not diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding how rumen microbial communities contribute to methane production and how these microbes are influenced by diet is essential for the rational design of methane mitigation strategies from livestock.

Postoperative nausea and vomiting in paediatric surgical inpatients.

A prospective study of postoperative nausea and vomiting (PONV) was conducted in 415 children presenting for inpatient surgery. The overall incidence of PONV was 18.1%). The highest incidence was in children undergoing ENT procedures and increased with age. Avoidance of intraoperative opioids and the use of local anaesthesia and/or non-steroidal anti-inflammatory drugs reduced the incidence of nausea and vomiting postoperatively.

An evaluation of a new self-adhesive patch preparation of amethocaine for topical anaesthesia prior to venous cannulation in children.

A new preparation of amethocaine in the form of a self-adhesive patch, designed to provide topical cutaneous anaesthesia prior to venous cannulation, was evaluated in an open study of 189 children. The new preparation of amethocaine was in place for a mean time of 48 min (SD 3.9). Eighty percent of patients had a satisfactory degree of analgesia for venous cannulation. Nine percent of patients experienced moderate pain and 11% experienced severe pain during venous cannulation. In 26% of patients there was slight (24%) or moderate (2%) erythema at the site of application, and in 5% slight oedema was noted at the site of application. Eight percent of patients had slight itching and 1% had moderate itching at the site of application. There was a clinical impression that venous dilatation made cannulation easier than with EMLA cream. These results suggest that this convenient preparation of amethocaine is highly effective at providing adequate topical cutaneous anaesthesia with a short onset time and a low incidence of minor side effects with no evidence of systemic toxicity.

Dietary n-3 fatty acid supplementation reduces superoxide production and chemiluminescence in a monocyte-enriched preparation of leukocytes.

Consuming substantial quantities of n-3 fatty acids reduces atherogenesis in experimental models of atherosclerosis. The mechanisms of this beneficial effect remain uncertain. Monocyte-derived tissue macrophages are associated with atherogenesis, and inhibition of monocyte inflammatory activity could, hypothetically, be helpful in preventing atherosclerosis. We observed that stimulated human monocyte and/or macrophage production of superoxide and the occurrence of monocyte chemiluminescence, two indices of monocyte inflammatory activity, were significantly reduced by the ingestion of 6 g n-3 fatty acids/d for 6 wk. This effect was associated with a reduction of stearic and arachidonic acids whereas eicosapentaenoic and docosahexaenoic acid concentrations rose significantly. These results indicate that modest dietary n-3 fatty acid supplementation can reduce stimulated human-monocyte free-radical production and may impair the capability of macrophages derived from monocytes to promote oxidation of low-density-lipoprotein cholesterol and associated cellular toxicity.

Dietary supplementation with omega-3 fatty acids prolongs platelet survival in hyperlipidemic patients with atherosclerosis.

Enhanced dietary omega-3 fatty acid consumption is thought to be associated with a reduced incidence of atherothrombotic disorders. This effect may be mediated in part through suppression of in vivo platelet activity by omega-3 fatty acids. We observed that platelet survival, a sensitive indicator of in vivo platelet activity was prolonged from 6.4 +/- 1.5 days to 7.7 +/- 1.4 days by moderate amounts of dietary omega-3 fatty acid supplementation for 6 weeks in a group of hyperlipidemic patients with preexisting, established atherothrombotic disorders. This effect on platelet survival was associated with a decrease in platelet arachidonic acid levels from 26.7 +/- 3.5% to 20.9% +/- 2.5% and a rise in platelet eicosapentaenoic and docosahexaenoic acid measurements from essentially undetectable to 2.8% +/- 1.6% and 1.9% +/- 1.0%. Plasma total cholesterol, low-density lipoprotein cholesterol, and serum apolipoprotein B levels rose significantly during the omega-3 fatty acid supplementation period. Platelet aggregation did not change. This study demonstrates that a modest amount of dietary omega-3 fatty acid supplementation can significantly effect in vivo platelet activity in a population at high risk for recurrent atherothrombotic disorders.

Effects of tristearin, triolein and safflower oil diets on cholesterol balance in rats.

Diets containing relatively homogeneous triglycerides composed of 18-carbon chain saturated, monounsaturated or polyunsaturated fatty acids were fed to rats. Cholesterol absorption and turnover were studied. Cholesterol absorption was significantly less in rats fed tristearin than in animals fed triolein or safflower oil. Cholesterol removal from plasma was fastest in rats fed tristearin and slowest with safflower oil and triolein. Plasma cholesterol levels were lowest with tristearin and highest with safflower oil. Increased cholesterol in high density lipoproteins was observed with tristearin and triolein. Lymph and hepatic cholesterol, and lymph triglycerides were highest with safflower oil, suggesting endogenous mobilization. Cholesterol production was least with triolein. Sterol synthesis was greatest with tristearin, perhaps attributable to decreased negative feedback analogous to effects of cholestyramine. Differences in lipoprotein composition observed with the various diets are important since effects on particle size and shape may influence removal mechanisms. The mechanisms underlying the different effects of dietary triglycerides on sterol absorption and metabolism remain to be elucidated.