What is the medical evidence on non-therapeutic child circumcision?

Non-therapeutic circumcision refers to the surgical removal of part or all of the foreskin, in healthy males, where there is no medical condition requiring surgery. The arguments for and against this practice in children have been debated for many years, with conflicting and conflicted evidence presented on both sides. Here, we explore the evidence behind the claimed benefits and risks from a medical and health-related perspective. We examine the number of circumcisions which would be required to achieve each purported benefit, and set that against the reported rates of short- and long-term complications. We conclude that non-therapeutic circumcision performed on otherwise healthy infants or children has little or no high-quality medical evidence to support its overall benefit. Moreover, it is associated with rare but avoidable harm and even occasional deaths. From the perspective of the individual boy, there is no medical justification for performing a circumcision prior to an age that he can assess the known risks and potential benefits, and choose to give or withhold informed consent himself. We feel that the evidence presented in this review is essential information for all parents and practitioners considering non-therapeutic circumcisions on otherwise healthy infants and children.

The impact of radical prostatectomy on the social well-being of prostate cancer survivors: A qualitative meta-synthesis.

INTRODUCTION: The impact of radical prostatectomy on the social well-being of survivors remains poorly understood. This meta-synthesis therefore aimed to integrate the findings of qualitative research evaluating the impact of surgery on the patient relationships with partners, family and wider societal interactions. METHODS: Medline, CINAHL, PsycINFO and Embase were searched for qualitative studies evaluating social well-being dimensions. A thematic meta-synthesis was conducted to inductively construct descriptive themes and overarching analytical themes. RESULTS: Thirty-one articles were included, with seven descriptive themes under two analytical themes generated to describe the experiences of 469 participants. 'Pathway to Conversion' encompassed three themes on the evolving social behaviour of men with both partners and family to adapt to their new normality postoperatively. 'A Man on My Own' discussed four themes focussing on both intimate and wider social relations, describing the stigma, shame and embarrassment felt by patients due to changes in their perceived body image and physical function. This resulted in men feeling alone, unsupported and seeking isolation. CONCLUSION: Radical prostatectomy's impact on survivors' social well-being extends beyond surgery and causes a shift in their relationship dynamics with partner and family, highlighting the importance of preoperative and postoperative clinician's counselling to both patient and partner.

A Rare Case of a Large Primary Renal Neuroendocrine Tumour: A Case Report and Brief Review of Literature.

Primary renal neuroendocrine tumours are very rare clinical entities, and as such, relatively little is known about their clinical progression. Here, we outline the case of a young female patient presenting with abdominal pain and a large 14 cm right renal mass. Initial radiological studies demonstrated localised disease, but during surgical resection, widespread liver metastasis was identified. Histological analysis revealed a grade 2, well-differentiated neuroendocrine tumour pT3a. Whilst surgical resection remains the gold standard for localised disease, further work is required to understand the pathogenesis, prognostic indicators and treatment following metastatic spread. The poor prognosis seen in primary renal neuroendocrine neoplasia highlights the importance of further directed research in this area.

Sharing a Context with Other Rewarding Events Increases the Probability that Neutral Events will be Recollected.

Although reward is known to enhance memory for reward-predicting events, the extent to which such memory effects spread to associated (neutral) events is unclear. Using a between-subject design, we examined how sharing a background context with rewarding events influenced memory for motivationally neutral events (tested after a 5 days delay). We found that sharing a visually rich context with rewarding objects during encoding increased the probability that neutral objects would be successfully recollected during memory test, as opposed to merely being recognized without any recall of associative detail. In contrast, such an effect was not seen when the context was not explicitly demarcated and objects were presented against a blank black background. These qualitative changes in memory were observed in the absence of any effects on overall recognition (as measured by d'). Additionally, a follow-up study failed to find any evidence to suggest that the mere presence of a context picture in the background during encoding (i.e., without the reward manipulation) produced any such qualitative changes in memory. These results suggest that reward enhances recollection for rewarding objects as well as other non-rewarding events that are representationally linked to the same context.

Increasing the efficiency of heterologous promoters in actinomycetes.

An Escherichia coli-actinomycete shuttle vector, pCJW93, was constructed which places cloned genes under the control of the thiostrepton-inducible tip promoter from Streptomyces lividans. We also constructed expression vectors bearing the actII-ORF4/PactI activator-promoter system of the actinorhodin biosynthetic pathway of Streptomyces coelicolor. With both types of vector, levels of expression varied widely in different actinomycete strains, indicating different levels of the host factors needed for optimal expression. Deletion of the actII-ORF4 activator gene from one such plasmid in Saccharopolyspora erythraea drastically reduced expression from the cognate actI promoter, showing that host factors are required for optimal production of the activator protein itself. However, a low copy number expression vector pWIZ1 for the polyketide synthase DEBS1-TE, in which the promoter for the activator gene was replaced by the strong heterologous ermE* promoter of S. erythraea directed highly efficient production of polyketide synthase protein in Streptomyces cinnamonensis; and the levels of triketide lactone product found were up to 100-fold greater than were produced by the same plasmid in which actII-ORF4 was expressed from its own promoter. Ensuring appropriate expression of a specific activator protein should enable more convenient and consistent heterologous expression of genes in a broad range of actinomycete hosts.

Stereochemistry of catalysis by the ketoreductase activity in the first extension module of the erythromycin polyketide synthase.

Multiple ketoreductase activities play a crucial role in establishing the stereochemistry of the products of modular polyketide synthases (PKSs), but there has been little systematic scrutiny of catalysis by individual ketoreductases. To allow this, a diketide synthase, consisting of the loading module, first extension module, and the chain-terminating thioesterase of the erythromycin-producing PKS of Saccharopolyspora erythraea, has been expressed and purified. The DNA encoding the ketoreductase-1 domain in this construct is flanked by unique restriction sites so that another ketoreductase domain can be readily substituted. The purified recombinant diketide synthase catalyzes, at a very low rate (k(cat) equals 2.5 x 10(-3) s(-1)), the specific production of the diketide (2S,3R)-2-methyl-3-hydroxypentanoic acid. The activity of the ketoreductase domain in this model synthase was analyzed using as a model substrate (+/-)-2-methyl-3-oxopentanoic acid N-acetylcysteaminyl (NAC) ester for which k(cat)/K(m) was 21.7 M(-1) s(-1). The NAC thioester of (2S,3R)-2-methyl-3-hydroxypentanoic acid was the major product and was strongly preferred over other stereoisomers as a substrate in the reverse reaction. The bicyclic ketone (9RS)-trans-1-decalone, a known substrate for ketoreductase in fatty acid synthase, was found also to be an effective substrate for the ketoreductase of the diketide synthase. Only the (9R)-trans-1-decalone was reduced, selectively and reversibly, to the (1S,9R)-trans-decalol. The stereochemical course of reduction and oxidation is exactly as found previously for the ketoreductase of animal fatty acid synthase, an additional indication of the close similarity of these enzymes.