Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data.

Background: It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.

Methods: We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing.

Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands.

Background: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose.

Adherence to antiretroviral therapy and acceptability of planned treatment interruptions in HIV-infected children.

There have been no paediatric randomised trials describing the effect of planned treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56). Carers, and children if appropriate, completed questionnaires on adherence to ART and acceptability of PTIs.

Involvement of consumers in studies run by the Medical Research Council Clinical Trials Unit: results of a survey.

Background: We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs), meta-analyses and other studies carried out by the UK Medical Research Council (MRC) Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV.

Methods: Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009) were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research.

The metabolic transition during disease following infection of Arabidopsis thaliana by Pseudomonas syringae pv. tomato.

The outcome of bacterial infection in plants is determined by the ability of the pathogen to successfully occupy the apoplastic space and deliver a constellation of effectors that collectively suppress basal and effector-triggered immune responses. In this study, we examined the metabolic changes associated with establishment of disease using analytical techniques that interrogated a range of chemistries. We demonstrated clear differences in the metabolome of Arabidopsis thaliana leaves infected with virulent Pseudomonas syringae within 8 h of infection.

Rapid linkage of indole carboxylic acid to the plant cell wall identified as a component of basal defence in Arabidopsis against hrp mutant bacteria.

Changes occurring to plant cell walls were examined following inoculation of Arabidopsis leaves with pathogenic and non-pathogenic (hrpA mutant) strains of Pseudomonas syringae pv. tomato. We have targeted low molecular weight, cross-linked phenolic and indolic compounds that were released from wall preparations by alkaline hydrolysis at 70 degrees C and in a microwave bomb.

Agroinfiltration reduces ABA levels and suppresses Pseudomonas syringae-elicited salicylic acid production in Nicotiana tabacum.

Background: Agrobacterium tumefaciens strain GV3101 (pMP90) is widely used in transient gene expression assays, including assays to study pathogen effectors and plant disease resistance mechanisms. However, inoculation of A. tumefaciens GV3101 into Nicotiana tabacum (tobacco) leaves prior to infiltration with pathogenic and non-host strains of Pseudomonas syringae results in suppression of macroscopic symptoms when compared with leaves pre-treated with a buffer control.

PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged.

A rapid and robust method for simultaneously measuring changes in the phytohormones ABA, JA and SA in plants following biotic and abiotic stress.

We describe an efficient method for the rapid quantitative determination of the abundance of three acidic plant hormones from a single crude extract directly by LC/MS/MS. The method exploits the sensitivity of MS and uses multiple reaction monitoring and isotopically labelled samples to quantify the phytohormones abscisic acid, jasmonic acid and salicylic acid in Arabidopsis leaf tissue.

Stabilisation of transition states prior to and following eudesmane cation in aristolochene synthase.

The mechanistic details of the cyclisation of farnesylpyrophosphate (FPP) by aristolochene synthase (AS) from Penicillium roqueforti have only recently begun to emerge, mainly through the analysis of the reaction products generated by AS-mutants. The reaction proceeds through several intermediates including germacrene A and eudesmane cation. Previous work suggested that the side chain of phenylalanine 178 promoted the conversion of eudesmane cation to aristolochene.

Dual role for phenylalanine 178 during catalysis by aristolochene synthase.

A mutant of aristolochene synthase, in which Phe 178 was replaced by Val, produced significant amounts of alpha-and beta-farnesene as well as alpha and beta-selinene and selina-4,11-diene, suggesting that Phe 178 is involved in the stabilisation of transition states preceding germacrene A and following eudesmane cation.

Stabilisation of eudesmane cation by tryptophan 334 during aristolochene synthase catalysis.

Analysis of the hydrocarbons produced during catalysis by mutants of aristolochene synthase from Penicillium roqueforti indicated that Trp 334 had a pivotal function for the efficient production of aristolochene from farnesylpyrophosphate most likely by stabilising the intermediate, eudesmane cation.