A Psychosexual Rehabilitation Booklet Increases Vaginal Dilator Adherence and Knowledge in Women Undergoing Pelvic Radiation Therapy for Gynaecological or Anorectal Cancer: A Randomised Controlled Trial.

AIMS: Women treated with pelvic radiation therapy (PRT) for gynaecological or anorectal cancer report a high number of sexual problems and unmet post-treatment psychosexual information needs. Currently, there is suboptimal adherence to recommended rehabilitation aids, such as vaginal dilators, and a paucity of resources to facilitate post-radiation rehabilitation and reduce distress in this population. This randomised controlled trial aimed to evaluate the effectiveness of a study-developed psychosexual rehabilitation booklet in this setting. MATERIALS AND METHODS: Eighty-two women scheduled for PRT to treat gynaecological/anorectal cancer were randomised to receive the intervention booklet (n = 44) or standard information materials (n = 38). Self-report questionnaires administered at pre-treatment baseline and at 3, 6 and 12 months post-treatment assessed adherence with rehabilitation aids, booklet knowledge, anxiety, depression and sexual functioning/satisfaction. RESULTS: Dilator adherence and booklet knowledge were significantly higher in the intervention group than in the control group (averaged over time points), with scores significantly increasing over time. Younger age and gynaecological cancer were significant predictors of greater dilator adherence. No significant group differences were found on psychological and sexual measures. CONCLUSIONS: The psychosexual rehabilitation booklet was effective in educating women with gynaecological and anorectal cancers about PRT-related psychosexual side-effects and rehabilitation options, as well as promoting uptake of vaginal dilator use. Future research should elucidate the effectiveness of this booklet in women with greater psychological and sexual functioning needs.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

BACKGROUND: To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. METHODS: Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. FINDINGS: 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. INTERPRETATION: Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.

Interleukin-18 genetics and inflammatory disease susceptibility.

IL18 was mapped to 11q22.2-22.3 in 1998. Owing to interleukin (IL)-18's important and novel role in immunomodulation, the gene itself has been subject to scrutiny, with the aim of discovering variants that may impact on disease susceptibility and/or progression. Despite being sequenced numerous times in different populations, no non-synonymous variants have been found. However, a number of polymorphisms within the proximal promoter have been verified that may interfere with transcription-factor-binding sites. Much of the subsequent association analyses have centred on these variants, but have yielded no consistent results, despite numerous different study populations being genotyped. IL18 has recently been resequenced in its entirety, enabling the tagging-single-nucleotide polymorphism (tSNP) methodology to be adopted. This approach has yielded interesting results, with genetic variation being shown to affect protein levels, and risk. This review aims to compile and reflect on the association data of interest published to date, with a focus on the diseases related to aberrant inflammatory control.

Perforating small bowel injuries in children: influence of time to operation on outcome.

The purpose of this study was to determine whether delay in the diagnosis of small bowel injury (SBI) affected the outcome of paediatric patients who required surgical interventions in the treatment of small bowel injuries. A retrospective chart review was performed on children with traumatic SBI requiring surgical management between January 2000 and December 2002. Diagnostic interval was defined as the time from presentation to operative treatment and delay was an interval of greater than 8 h. Thirteen patients were admitted for operative treatment of SBI. Nine cases were the result of motor vehicle trauma. The mean diagnostic interval for all patients was 9.1 h+/-7.4 h (range 0.6 h-22.5 h). Six patients had a diagnostic delay with a mean diagnostic interval of 15.5 h+/-5.5 h. There was no statistically significant difference found between the prompt and delayed diagnosis groups in terms of complications or length of hospital stay. Our finding of no difference between the prompt and delayed diagnosis groups and a diagnostic delay no longer than 22.5 h may suggest that our local methods of diagnosis and treatment assist in the prevention of unnecessary complications and death.

Internal initiation in Saccharomyces cerevisiae mediated by an initiator tRNA/eIF2-independent internal ribosome entry site element.

Internal initiation of translation can be mediated by specific internal ribosome entry site (IRES) elements that are located in certain mammalian and viral mRNA molecules. Thus far, these mammalian cellular and viral IRES elements have not been shown to function in the yeast Saccharomyces cerevisiae. We report here that a recently discovered IRES located in the genome of cricket paralysis virus can direct the efficient translation of a second URA3 cistron in dicistronic mRNAs in S. cerevisiae, thereby conferring uracil-independent growth. Curiously, the IRES functions poorly in wild-type yeast but functions efficiently either in the presence of constitutive expression of the eIF2 kinase GCN2 or in cells that have two initiator tRNA(met) genes disrupted. Both of these conditions have been shown to lower the amounts of ternary eIF2-GTP/initiator tRNA(met) complexes. Furthermore, tRNA(met)-independent initiation was also observed in translation-competent extracts prepared from S. cerevisiae in the presence of edeine, a compound that has been shown to interfere with start codon recognition by ribosomal subunits carrying ternary complexes. Therefore, the cricket paralysis virus IRES is likely to recruit ribosomes by internal initiation in S. cerevisiae in the absence of eIF2 and initiator tRNA(met), by the same mechanism of factor-independent ribosome recruitment used in mammalian cells. These findings will allow the use of yeast genetics to determine the mechanism of internal ribosome entry.

Poly(A) polymerase and the regulation of cytoplasmic polyadenylation.

Translational activation in oocytes and embryos is often regulated via increases in poly(A) length. Cleavage and polyadenylation specificity factor (CPSF), cytoplasmic polyadenylation element binding protein (CPEB), and poly(A) polymerase (PAP) have each been implicated in cytoplasmic polyadenylation in Xenopus laevis oocytes. Cytoplasmic polyadenylation activity first appears in vertebrate oocytes during meiotic maturation. Data presented here shows that complexes containing both CPSF and CPEB are present in extracts of X. laevis oocytes prepared before or after meiotic maturation. Assessment of a variety of RNA sequences as polyadenylation substrates indicates that the sequence specificity of polyadenylation in egg extracts is comparable to that observed with highly purified mammalian CPSF and recombinant PAP. The two in vitro systems exhibit a sequence specificity that is similar, but not identical, to that observed in vivo, as assessed by injection of the same RNAs into the oocyte. These findings imply that CPSFs intrinsic RNA sequence preferences are sufficient to account for the specificity of cytoplasmic polyadenylation of some mRNAs. We discuss the hypothesis that CPSF is required for all polyadenylation reactions, but that the polyadenylation of some mRNAs may require additional factors such as CPEB. To test the consequences of PAP binding to mRNAs in vivo, PAP was tethered to a reporter mRNA in resting oocytes using MS2 coat protein. Tethered PAP catalyzed polyadenylation and stimulated translation approximately 40-fold; stimulation was exclusively cis-acting, but was independent of a CPE and AAUAAA. Both polyadenylation and translational stimulation required PAPs catalytic core, but did not require the putative CPSF interaction domain of PAP. These results demonstrate that premature recruitment of PAP can cause precocious polyadenylation and translational stimulation in the resting oocyte, and can be interpreted to suggest that the role of other factors is to deliver PAP to the mRNA.

Sleep as a teaching tool for integrating respiratory physiology and motor control.

Sleep exerts major effects on most fundamental homeostatic mechanisms. Current data suggest, however, that students of physiology and medicine typically receive little or no formal teaching in sleep. Because sleep takes up a significant component of our life span, it is proposed that current teaching in systems and integrative physiology is not representative if it is confined to functions describing wakefulness only. We propose that sleep can be readily integrated into various components of physiology and medical curricula simply by emphasizing how commonly taught physiological processes are importantly affected by sleep mechanisms. In our experience, this approach can be used to reinforce basic physiological principles while simultaneously introducing sleep physiology into the students' training. We find that students have a general and inherent interest in sleep and related clinical disorders, and this proves useful as an effective means to teach the material. In this paper, examples of how sleep influences motor control and the respiratory system will illustrate these points. These considerations also highlight some important gaps in traditional teaching of respiratory physiology.

Regulation of host cell translation by viruses and effects on cell function.

Viruses have evolved a remarkable variety of strategies to modulate the host cell translation apparatus with the aim of optimizing viral mRNA translation and replication. Recent studies have revealed that modulation of both host and viral mRNA translation can be accomplished by selective alteration of translation factors in virus-infected cells. These findings provide new insights into the functioning of the translational apparatus in both uninfected and infected cells.

Rapid deadenylation and Poly(A)-dependent translational repression mediated by the Caenorhabditis elegans tra-2 3' untranslated region in Xenopus embryos.

The 3' untranslated region (3'UTR) of many eukaryotic mRNAs is essential for their control during early development. Negative translational control elements in 3'UTRs regulate pattern formation, cell fate, and sex determination in a variety of organisms. tra-2 mRNA in Caenorhabditis elegans is required for female development but must be repressed to permit spermatogenesis in hermaphrodites. Translational repression of tra-2 mRNA in C. elegans is mediated by tandemly repeated elements in its 3'UTR; these elements are called TGEs (for tra-2 and GLI element). To examine the mechanism of TGE-mediated repression, we first demonstrate that TGE-mediated translational repression occurs in Xenopus embryos and that Xenopus egg extracts contain a TGE-specific binding factor. Translational repression by the TGEs requires that the mRNA possess a poly(A) tail. We show that in C. elegans, the poly(A) tail of wild-type tra-2 mRNA is shorter than that of a mutant mRNA lacking the TGEs. To determine whether TGEs regulate poly(A) length directly, synthetic tra-2 3'UTRs with and without the TGEs were injected into Xenopus embryos. We find that TGEs accelerate the rate of deadenylation and permit the last 15 adenosines to be removed from the RNA, resulting in the accumulation of fully deadenylated molecules. We conclude that TGE-mediated translational repression involves either interference with poly(A)'s function in translation and/or regulated deadenylation.

International harmonization issues.

With the globalization of trade in many product sectors occurring at a rapid pace, interest in international harmonization issues relating to veterinary products continues to grow. Because of the potential impact on trade, there has been a focus for several years on harmonization of maximum residue limits (MRLs) or tolerances on a global basis. There has also been interest, especially on the part of pharmaceutical companies, to facilitate the approval of a veterinary product in multiple countries. This article discusses two major international initiatives that have been formed to address these harmonization areas of concern for veterinary products.

Evolutionary conservation of sequence elements controlling cytoplasmic polyadenylylation.

Cytoplasmic polyadenylylation is an evolutionarily conserved mechanism involved in the translational activation of a set of maternal messenger RNAs (mRNAs) during early development. In this report, we show by interspecies injections that Xenopus and mouse use the same regulatory sequences to control cytoplasmic poly(A) addition during meiotic maturation. Similarly, Xenopus and Drosophila embryos exploit functionally conserved signals to regulate polyadenylylation during early post-fertilization development. These experiments demonstrate that the sequence elements that govern cytoplasmic polyadenylylation, and hence one form of translational activation, function across species. We infer that the requisite regulatory sequence elements, and likely the trans-acting components with which they interact, have been conserved since the divergence of vertebrates and arthropods.

Coat protein of cauliflower mosaic virus binds to ssDNA.

Alkali-denatured cauliflower mosaic virus (CaMV) virions incorporated ssDNA, added exogenously, into multimolecular complexes during dialysis against a neutral buffer. CaMV coat protein binding to tracer DNA, assessed by gel electrophoresis and autoradiography, was highly cooperative as judged by the absence of intermediate-sized complexes. The incorporation of labelled BglII fragments of a plasmid containing CaMV DNA into complexes was prevented by the presence of 0.16 g/l unlabelled calf thymus DNA. Lower concentrations of competitor DNA allowed binding of some BglII fragments although preventing the binding of others. The self-annealing poly(dI-dC) was much less efficient than calf thymus DNA in preventing the incorporation of fragments into complexes, suggesting a binding preference for ss- over dsDNA. In addition, dsDNA, minimally cross-linked to prevent strand separation, was bound only weakly. End-labelled ssDNA fragments in complexes were partially protected against DNase I. The nucleic acid-binding activity of CaMV coat protein may be responsible for the organization of replication complexes, the precursors to virion particles.

A phantom for the measurement of contrast detail performance in film-screen mammography.

A National Breast Cancer Screening Programme, based on X-ray mammography, has been introduced in the UK. The success of this screening programme is dependent on the production of high quality radiographs. There are various methods of assessing imaging performance in mammography, but contrast detail detectability measurements have an advantage in that the observation of radiographs is taken into consideration. The design and construction of a contrast detail phantom for the assessment of image quality in mammography is described. This phantom can be used to assess the imaging performance of mammographic film-screen combinations. The results of some measurements to verify the accuracy of the contrast predictions are presented together with some initial results of an investigation into the contrast detail performance of film-screen combinations used in mammography.

An instrument for monitoring the force applied by breast compression devices on mammography x-ray sets.

Automatic breast compression devices are commonly fitted to mammographic x-ray sets. The force exerted by these compression devices should be limited and periodically checked. This article describes the design and construction of an instrument for the routine assessment of the force applied by breast compression devices on mammography x-ray sets. Results obtained on four different mammography x-ray units are presented. In addition, data on the effect of compression plate design on compression force is given for one unit. The instrument has proved to be a simple and quick method of monitoring the force applied by the compression plates on mammographic x-ray units.