Physiotherapy Assessment and Management of Post- Prostatectomy Urinary Incontinence

Aim: To determine the reliability of scoring real-time ultrasound (RTUS) record during an exercise protocol aimed at developing pelvic floor motor control in men with prostate cancer, and to determine predictors of acquiring control. Methods: 91 men diagnosed with prostate cancer attending physiotherapy for pelvic floor exercises. Detailed pelvic floor motor control exercises were taught by a physiotherapist to participants using trans-abdominal RTUS for biofeedback. A new protocol to measure skill attainment was developed. Three independent physiotherapists assessed skill attainment by viewing RTUS videos of the exercise. Reliability was evaluated using intraclass correlation coefficients. Logistic regression analysis was conducted to identify predictors of successful skill attainment. Acquisition of the skill was compared between pre and post-operative participants using an independent-groups t-test. Results: There was good reliability for scoring the outcome method (ICC 0.73 (95%CI 0.59 - 0.82)) for experienced therapists. Having low BMI and being seen pre- operatively predicted motor skill attainment, accounting for 46.3% of the variance. Significantly more patients trained pre-operatively acquired the skill of pelvic floor control compared with patients initially seen post-operatively (OR 11.87 95%CI 1.4 to 99.5 p = 0.02). Conclusions: A new protocol to evaluate attainment of pelvic floor control in men with prostate cancer can be scored reliably from RTUS record, and is most effective delivered pre-operatively. Future Studies: Based on the above research a proposed RCT has been developed comparing current standard pelvic floor training protocols with a motor control led training protocol. This protocol is followed by development into a progressive resistance program that utilises progressively incremental intra- abdominal pressures as a resistance tool. Further discussion is made to evaluate optimal pelvic floor rehabilitative strategies

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.The Human Papillomavirus Research Group at the University of Cambridge is funded by the UK Medical Research Council.This is the final version of the article. It first appeared from MDPI via http://dx.doi.org/10.3390/v707280

Host control of human papillomavirus infection and disease

Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state.Support by the Medical Research Council (programme grant U117584278) has allowed the formulation of many of the ideas outlined in this review

'They wouldn't know how it feels . . .': characteristics of quality care from young people's perspectives: a participatory research project

Literature suggests there is a need to hear from children themselves about the quality of healthcare they receive and, although their views are increasingly sought, little is known about children’s definitions of ‘high or low quality care’. This article reports on a participatory, qualitative study that set out to explore with children and young people whether they could be involved in monitoring the quality of hospital care. Nine young people played an active role in the research process, collecting data from an additional 129 participants aged between 9 and 14. Five characteristics of quality care were identified: ‘technical expertise’, ‘friendly staff ’, ‘respect’, ‘choice’ and ‘explanations’

Synthesis of Viral DNA and Late Capsid Protein L1 in Parabasal Spinous Cell Layers of Naturally Occurring Benign Warts Infected with Human Papillomavirus Type 1

AbstractWe investigated human papillomavirus type 1 (HPV1)-specific transcription, viral DNA replication, and viral protein expression in naturally occurring benign tumors by in situ hybridization, 5-bromodeoxyuridine (BrdU) incorporation, and immunohistochemistry and obtained results different from other HPV-infected benign tumors characterized so far. Moderate amounts of transcripts with a putative coding potential for E6/E7, E1, and E2 were demonstrated from the first subrabasal cell layer throughout the stratum spinosum and granulosum. In addition very large amounts of E4 and L1 transcripts were present in the same epithelial layers. This finding was substantiated by the demonstration of L1 and E4 protein already in the bottom-most spinous cell layer. Furthermore massive amplification of the viral DNA as measured by BrdU incorporation and different methods of in situ hybridization took place in the lowest 5 to 10 suprabasal cell layers. These findings are in contrast to the assumption that late gene expression and viral DNA synthesis are restricted to the more differentiated cell layers of the epithelium and point to differences in the regulation of the vegetative life cycle between different papillomavirus types

Microstructural characterisation of metallic shot peened and laser shock peened Ti–6Al–4V

A detailed analysis has been conducted of Ti–6Al–4V processed by metallic shot peening and laser shock peening. Analysis by incremental hole drilling, electron backscattered diffraction microscopy, transmission electron microscopy and transmission Kikuchi diffraction microscopy is evaluated and discussed. The results of this analysis highlight the very different dislocation structures in surfaces processed by these two techniques. Transmission Kikuchi diffraction also has been used to evaluate sub-grains generated by laser shock peening. A notable feature of material processed by laser shock peening is the almost complete absence of deformation twinning, contrasting with the frequent observation of extensive deformation twinning observed in the material processed by metallic shot peening.This work was supported by the Rolls-Royce plc/EPSRC strategic partnership under EP/H022309/1

Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance

AbstractThe E6 protein from high-risk human papillomaviruses appears necessary for persistence of viral episomes in cells but the underlying mechanism is unclear. E6 has many activities, including its ability to bind and degrade PDZ domain-containing proteins, such as hScrib. However little is known about the role of these interactions for E6 function and the viral life cycle. We now show that the levels of expression of wild-type E6 are increased in the presence of hScrib whilst a mutant E6 protein lacking the PDZ-binding motif is found at lower levels as it is turned over more rapidly by the proteasome. This correlates with an inability of genomes containing this mutation to be maintained as episomes. These results show that E6 association with certain PDZ domain-containing proteins can stabilize the levels of E6 expression and provides one explanation as to how the PDZ-binding capacity of E6 might contribute to genome episomal maintenance