Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.

Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts - which are limited by their availability - for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5 Hz, 1h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage.

Amplifying the Patient Voice: A Survey of Practitioners' Use of Patient-reported Outcome Measures Across Radiotherapy Providers in England.

AIMS: The NHS England Radiotherapy Service Specification calls for routine use of patient-reported outcome measures (PROMs). However, barriers exist at patient, healthcare professional and service levels. The aim of the present study was to determine the current use of PROMs within radiotherapy services in England. The current attitudes, barriers and enablers to the implementation of PROMs in radiotherapy practice were evaluated and practical recommendations to inform future implementation were developed. MATERIALS AND METHODS: A mixed-methods approach was adopted to obtain quantitative and qualitative data. An online questionnaire was developed and disseminated to all radiotherapy operational delivery network managers across England. The questionnaire consisted of 12 open and closed questions relating to PROMs use, with the option to provide free-text responses. Inductive thematic analysis was conducted on free-text comments, whereas descriptive statistics were used to analyse quantitative data. RESULTS: In total, 182 responses were received from 40 of the 50 radiotherapy providers, resulting in a response rate of 84%. The current use of PROMs was analysed, including rationale for use, tools used, format of PROMs collection and timing within the radiotherapy pathway. Most respondents indicated that PROMs were used in the context of clinical trials only. Through thematic analysis, four identical key themes were identified relating to both barriers and enablers to PROMs use; these included IT infrastructure, time, human/financial resources and training/education. A fifth theme, standardisation, was identified as a key enabler to PROMs use. CONCLUSIONS: Our findings show that outside of clinical trials, PROMs are not routinely used in radiotherapy services due to barriers identified at professional and service levels. Here we provide recommendations to mitigate the barriers identified and implement PROMs in radiotherapy, including training for healthcare professionals and standardisation of PROMs tools and storage. This study provides a key first step in driving PROMs implementation within radiotherapy services across England.

The Patient's perspective: A review of the results from a radiotherapy patient experience survey in the North-West of England.

INTRODUCTION: A patient experience survey was undertaken for patients completing radiotherapy at the three Northwest of England Radiotherapy Providers. METHODS: A previously reported National Radiotherapy Patient Experience Survey was adapted and undertaken in the Northwest of England. Quantitative data was analysed to establish trends. Frequency distribution was applied to appraise the number of participants selecting each of the pre-determined responses. Thematic analysis of free text responses was conducted. RESULTS: The questionnaire received 653 responses from the 3 providers across seven departments. Thematic analysis revealed 3 themes; logistics, information and operational. CONCLUSION: The results indicate that the majority of patients are satisfied with their treatment and care. Patients' responses indicate areas for improvements. Expectancy theory states that an individual's satisfaction is related to the difference between expected service and the service received. Consequently, when reviewing services and developing improvement it is important to understand patients' expectations. This regional survey starts to capture what people receiving radiotherapy expect from the service and the professionals delivering their treatment. IMPLICATIONS FOR PRACTICE: This survey responses make a case for reviewing the information provision pre and post radiotherapy. This includes clarifying the understanding of consent for treatment including the intended benefits and potential late effects. There is an argument to offer information sessions prior to radiotherapy to achieve more relaxed and informed patients. A recommendation from this work is for the radiotherapy community undertake a national radiotherapy patient experience survey, facilitated via the 11 Radiotherapy ODNs. A national radiotherapy survey has multiple benefits to inform improvements in practice. This includes benchmarking services against national averages. This approach is aligned with the principles of the service specification in terms of reducing variation and increasing quality.

Barriers and facilitators to conducting radiotherapy clinical trials: Findings from a UK survey.

INTRODUCTION: As an essential component of service delivery, radiotherapy clinical trials were championed within the NHS England service specifications. A call for a 15% increase in research and clinical trial activity, alongside a demand for equity of access for patients with cancer subsequently ensued. National understanding of current radiotherapy clinical trials operational practices is absent, but essential to help establish the current provision required to support the development of a strategic plan for implementation of NHS England's specifications. METHODS: A cross-sectional survey was developed by a multi-disciplinary team and distributed to therapeutic radiography clinical trial leads across the UK to ascertain the current provision of radiotherapy clinical trials only, including workforce resources and the trials management processes to establish a benchmark and identify potential barriers, enablers, and opportunities to increase access to clinical trials. RESULTS: Thirty-two complete responses were obtained equating to 49% of the total UK NHS departments and 74% of those departments invited. Four key findings were identified: 1) research strategy and systems, 2) participation and activity in radiotherapy clinical trials, 3) access to clinical trials at alternative departments and 4) facilitators & barriers. Overarchingly a lack of radiotherapy clinical trials strategy or supported processes were apparent across the UK, aggravating existing barriers to trial activity. CONCLUSION: It is essential for radiotherapy clinical trials to be embedded in to departmental and Trust strategy, this will help to ensure the processes and resources required for trial delivery are not only in place, but also recognised as imperative and important for patients with cancer as radiotherapy treatment delivery. IMPLICATIONS FOR PRACTICE: Failure to address the barriers or build upon the facilitators may result in UK radiotherapy departments facing challenges in achieving the 15% increase in radiotherapy clinical trial activity.

Therapeutic radiographers supporting individuals undergoing radiotherapy to stop smoking: Testing a training resource in clinical practice.

INTRODUCTION: This study developed and piloted the first online training package to support implementation and delivery of brief smoking cessation interventions for therapeutic radiographers in four radiotherapy departments in England. METHODS: A previously reported systematic literature review and data analysis from the previously reported pre-focus group questionnaire and focus groups enabled the development of an online training package. The questionnaire was repeated by the participating therapeutic radiographers following completion of the training resource (n = 31). The results of the comparative questions from the pre and post questionnaires were analysed using the Statistical Package for Social Sciences (SPSS Version 24). RESULTS: In total, 43 therapeutic radiographer participants completed the pre-questionnaire and 31 participants continued to complete the post questionnaire, having completed the online training package. The previously conducted focus groups identified several barriers to the delivery of smoking cessation, that were addressed through the development of an online training package. Following the completion of the training; therapeutic radiographers had increased knowledge and confidence regarding smoking cessation, the number of therapeutic radiographers who believe that smoking cessation is part of their role increased and therapeutic radiographers more routinely have conversations about smoking cessation. CONCLUSION: The training resource improved therapeutic radiographers' knowledge and confidence and increased awareness of the role of the therapeutic radiographer in the provision of smoking cessation interventions. Challenges remain that continue to prevent some therapeutic radiographers from delivering smoking cessation interventions and strong leadership and implementation of strategy and guidance is essential to ensure wider implementation. Recording and measuring impact of interventions remains an area to be addressed, alongside cultural changes and reassurance around the therapeutic relationship. IMPLICATIONS FOR PRACTICE: This training tool has proven to be effective in the sample within this study and should be disseminated and evaluated more widely across radiotherapy provision within the United Kingdom.

Digital support for living with and beyond gynaecological cancer.

INTRODUCTION: Gynae-Radiotherapy places exceptional psychosocial and physical burdens on patients. Technological developments and associated acute toxicity and survival outcomes have improved, however holistic support has not kept pace. Digital technologies have potential to enhance support and patient experience. The project aimed to co-create a prototype of a digital health intervention that could serve the needs of women living with and beyond treatment for gynaecological cancer. METHODS: A multi-disciplinary and co-creation approach was adopted. Four workshops were held, comprising of a number of activities to support participants' expression of views and facilitate discussion. Methods included word cloud generation, prompt cards, empathy maps and persona creation, domain storylines and requirements identification. RESULTS: Support drops off dramatically once treatment is completed. Patients struggled to adjust to their 'new normal' and felt unprepared for changes post-treatment. Patients felt overwhelmed with leaflets yet wanted instant access to reliable and relevant information in one place, better information on late side effects and improved communication about sexual health and sexuality. Reassurance through a digital intervention was viewed positively and specific ideas for achieving this were suggested through: Sharing experiences; targeted practical advice; peer support and advice/support for significant others. CONCLUSION: The co-creation of a prototype generated further discussion and an interactive prototype was developed. Based on workshop findings it is believed that the intervention could provide life-long support for women living with and beyond cancer. IMPLICATIONS FOR PRACTICE: Increased focus is needed on the late effects of radiotherapy, specifically in supporting psychosocial wellbeing. Co-creation is a rewarding and fulfilling activity that met numerous aims beyond those of the project. It is recommended that mixed staff-patient groups are developed and adopted in more informal ways for the improvement of services.

Therapeutic Radiographers' perceptions of the barriers and enablers to effective smoking cessation support.

INTRODUCTION: Tobacco smoking during and post radiotherapy is associated with increased treatment toxicity and increased cancer related mortality. Routine delivery of smoking cessation advice is inconsistent in practice. This study identifies the key barriers and facilitators to the provision of effective smoking cessation conversations in radiotherapy practice. METHODS: A baseline questionnaire (n = 43) was used to identify current practice, barriers and facilitators to smoking cessation in radiotherapy and to inform a topic guide for follow up focus groups (n = 5). Ethical approval was obtained through the 4 NHS trusts and the Health Research Authority. Focus group transcription was coded by two researchers. RESULTS: Therapeutic Radiographers initiate health behaviour conversations with patients; there are a number of factors that facilitate the likelihood of a health behaviour conversation; indication that a patient smokes anatomical site and presence of acute effects. Key barriers to smoking cessation provision include; lack of training, limited knowledge, limitations as a result of poor clinical infrastructure, local culture and perceptions that patients do not prioritise smoking cessation during treatment. CONCLUSION: Therapeutic Radiographers have the motivation to provide smoking cessation advice, however they require further training to develop knowledge and skills in relation to benefits of smoking cessation and cessation strategies. Therapeutic Radiographers also expect that patients will respond negatively to smoking cessation advice, and that this might be damaging to the therapeutic relationship. Departmental culture and trust infrastructure can also significantly inhibit the provision of smoking cessation in radiotherapy practice and further support to implement NICE guidance is required.

Determining the optimal strategy for the live-attenuated herpes zoster vaccine in adults.

The optimal strategy for the vaccinating against herpes zoster (HZ) vaccine remains unknown. Cost-effectiveness analyses provide insight to the most cost-effective age groups but results vary across studies. The optimal strategy is important given that vaccine efficacy and duration vary depending on vaccination age. Therefore, small changes from the optimal age can affect long-term outcomes and produce sub-optimal results. The objective of this research was to determine the optimal timing policy for HZ vaccination. We simulated cohorts of men and women and use stochastic dynamic programming to evaluate the decision to vaccinate or defer each year from age 50 to 100. If the decision was to defer, the cohort risked developing HZ. If HZ occurred, the cohort was subjected to cost and quality-adjusted life year (QALY) loss for a typical HZ infection (including complications) at that age. If HZ did not occur, the decision was evaluated at the next age. Then, we extend the model to consider the case in which a booster vaccine is available. A set of probabilistic sensitivity analyses were conducted to check model robustness. Results show the optimal policy for women is to vaccinate between ages 66 and 77, and for men between ages 66 and 74, assuming a willingness to pay (WTP) of $100,000 per QALY. It becomes optimal to vaccinate earlier if a booster vaccine is available, and women have a wider range of ages than men. This research is the first to examine exactly when the HZ vaccine should be administered. It is also the first study, to our knowledge, that used stochastic dynamic programming to examine the question of a second dose for any vaccine. This research provides the first simple policy on when to vaccinate and re-vaccinate against HZ.

Attitudes of oncology healthcare practitioners towards smoking cessation: A systematic review of the facilitators, barriers and recommendations for delivery of advice and support to cancer patients.

OBJECTIVES: A systematic review of the literature was conducted. The review was conducted using a search of the literature for all years up to October 2016. Statements that identified facilitators, barriers or recommendations surrounding smoking cessation delivery were extracted and analogous statements aggregated to enable thematic analysis. After searching multiple databases and the application of exclusion and inclusion criteria, a total of 19 acceptable studies were identified. KEY FINDINGS: Delivery of cessation by oncology professionals was impacted by their own knowledge and views, their perception of the benefits to patient health and by the workplace procedures within their institution. CONCLUSION: Oncology practitioners worldwide face similar issues in delivering smoking cessation advice. By improving training programs that address the attitudes and beliefs which facilitate or block delivery of smoking cessation and by implementing systemic changes within cancer centres, delivery of smoking cessation should be enabled.

The MUC2 gene product: a human intestinal mucin.

The MUC2 gene product is the first human secretory mucin protein core to be fully sequenced. Like the other eight human MUC genes identified to date, MUC2 is characterised by tandem and irregular repeat sequences rich in threonine and serine, the potential sites of attachment of the oligosaccharide chains. The MUC2 gene product is more than 5100 amino acids in its commonest allelic form and accounts for one fifth by weight of the mucin glycoprotein molecule (80% oligosaccharide side chains). The MUC2 product is polymerised end to end through disulphide bridges to form large secreted polymeric gel-forming mucins (Mr approximately 10(7)). The primary function of the MUC2 gene product is to provide a protective barrier between the epithelial surfaces and the gut lumen. There is decreased expression of MUC2 in colonic cancer and defective polymerisation of secreted mucin in ulcerative colitis. Elucidation of the MUC2 and other mucin gene sequences has opened the way for a full structural characterisation and an improved understanding of the structure and function of these complex mucus gel secretions.

Free radicals in red wine, but not in white?

By using Electron Spin Resonance (ESR) spectroscopy, we have detected free radicals in red wine, whether fermented on oak or not, and in white wine only when it has been fermented on oak. These radicals would appear to be associated with the phenolics, because the ESR signal from the residue of red wine treated with polyvinyl polypyrrolidone is reduced by approximately 80%. Any inhibition of lipid oxidation by red wine phenolics in vitro will take place in the presence of these radicals, which have a linewidth of 2.0 +/- 0.1 gauss and a g-value of 2.0038 +/- 0.0001.

The chemical origin of free radicals in coffee and other beverages.

Sugars or carbohydrates are identified as the source of free radicals in coffees, ersatz coffees, a number of other food flavouring and colouring agents formed by processes involving heating, and in beers and stouts. The radicals are not derived from phenolic constituents, in contrast to those in wine, and are unlikely to be due solely to the occurrence of Maillard reactions.

Evaluation of chemically induced cytogenetic lesions in rabbit oocytes. III. A postimplantation analysis of streptonigrin effects.

The frequency of consistent structural chromosome aberrations was determined for 108 fetuses (day 14 of gestation) from 20 female rabbits treated before conception with 90 micrograms/kg of streptonigrin (NSC-45383). The findings by karyotype analysis of 1.85% of the fetuses with consistent aberrations was compared with 6.32% frequency previously observed in 6-day (preimplantation) blastocysts from identically treated females and found to be significantly reduced. The interpretation of the findings is that the developmental events of implantation and placentation are effective in eliminating from further gestation the majority of the rabbit conceptuses with consistent structural chromosome abnormalities. The data are also discussed relative to the predictive nature of somatic cell chromosome damage in women of childbearing age being an estimator of risk of producing offspring with structural chromosome aberrations. The data show that preconceptional treatment of female rabbits with streptonigrin caused a shift in the cytogenetically determined sex ratio of the 14-day fetuses, but not of the 6-day blastocysts. The significant decrease in relative numbers of males observed is consistent with the induction of lethal mutations on the X chromosome. This finding is discussed in conjunction with the timing and parental specificity of X chromosome inactivation during mammalian embryonic development.

Compositional differences between bilateral middle ear effusions in otitis media with effusion: evidence for a different etiology?

The aim of this study was to clarify the site of primary pathology in otitis media with effusion. Effusions were collected from 64 children with bilateral effusions at the time of myringotomy. The rheological properties and biochemical compositions of effusions were measured for 23 pairs of effusions, and the levels of the inflammatory mediators TNF alpha, IL-1beta, and IL-8 were measured in 41 pairs using specific enzyme-linked immunosorbent assays (ELISAs). Measurements from paired ears were compared using analysis of variance (ANOVA) tests and significant differences were found for reduced specific viscosity, mucin content, protein content, and levels of IL-8. The results demonstrate that the two ears have different immunological processes or rates of processes which might explain the significantly different rheological properties of effusions. This suggests that each ear undergoes pathological changes independently and has implications for using the opposite ear as a control in clinical trials.

Preliminary characterization of mucin from effusions of cleft palate patients.

Middle ear effusions from children undergoing myringotomy were classified into three groups-cleft palate, thick (mucoid), and thin (serous). Mucin was purified from each of the three groups using CsCI equilibrium density gradient centrifugation. Analysis of the cleft palate mucin on Sepharose CL-2B showed it was excluded and therefore of large molecular weight. It could be broken down into smaller glycopeptide units by proteolysis and these glycopeptides had, based on elution position, a larger hydrodynamic size than those from the thick mucin. Intrinsic viscosity measurements demonstrated that the intact mucins could be ranked in order of molecular space occupancy; cleft palate > thick > thin. Amino acid analysis showed the cleft palate mucin to have an amino acid composition similar to other mucins, with serine, threonine, and proline constituting 41% by weight of the protein core. Thiol analysis gave evidence of a possible difference in polymerization between the three mucins, in that thin (the smallest mucin) contained the lowest number of thiols. This preliminary analysis of cleft palate mucin suggests a mucin with larger glycopeptide units forming an intact mucin of larger hydrodynamic size than either thick or thin middle ear mucins from anatomically normal children.

Relationship of obesity and specimen weight to complications in reduction mammaplasty.

Obesity and specimen weight have both been associated with a higher incidence of complications for patients undergoing reduction mammaplasty. However, obesity has been arbitrarily and inconsistently defined, and the degree of obesity has not been considered in these previous studies. Because insurance companies are increasingly demanding weight loss before authorizing surgery, the relationship of obesity and breast size to complications is of great importance. Upon critical review of the literature, a number of fundamental questions remain unanswered. If complications are more frequent in the obese patient, are these complications directly proportional to the degree of obesity? Also, if the patient is required to lose weight before surgery, is weight loss effective in reducing complication rates? In an attempt to clarify these issues, 395 patients who underwent reduction mammaplasty over a 10-year period were reviewed retrospectively. Patients were arbitrarily divided into five groups in which, depending on their degree of relative obesity, they were classified as less than 5 percent, 5 to 10 percent, 10 to 15 percent, 15 to 20 percent, or greater than 20 percent above average body weight. To evaluate the relationship of specimen weight to complications, patients were also arbitrarily divided into five groups according to weight of the breast reduction specimen, which was classified as less than 300 g, 300 to 600 g, 600 to 900 g, 900 to 1200 g, and greater than 1200 g reduction per breast. Complications were then divided into local and systemic and major and minor. When bilateral reductions alone were analyzed (n = 267), there was a statistically significant increase in complication rate in the obese (p = 0.01). However, when the obese population was further subdivided according to their degree of obesity (less than 5 percent, 5 to 10 percent, 10 to 15 percent, 15 to 20 percent, and greater than 20 percent above average body weight), no further correlation was found. However, the relationship between specimen weight per breast and complications was much stronger with a direct correlation existing between increasing specimen weight and the incidence of complications. Although this study has shown that patients who are average body weight have fewer complications than obese patients after breast reduction surgery, it has not shown an increasing incidence of complication with increasing degrees of obesity. The implications of these findings and their relationship for denying patients surgery on the basis of weight alone are discussed in detail.

Otitis media with effusion: components which contribute to the viscous properties.

Middle ear effusions from children undergoing myringotomy were classified into thick (mucoid) and thin (serous) on the basis of their flow properties. Their composition was analysed and their rheological properties measured. The viscosity of the effusions was measured using a Contraves low shear viscometer and expressed as specific viscosity per mg/ml of non-dialysable solids present. In order to measure the effusion viscosity it was necessary to solubilize the effusion by mild homogenisation in a phosphate buffer pH 6.7 containing a cocktail of proteolytic inhibitors. The viscosity of mucoid effusions was significantly greater than that of the serous effusions. There was a small but measurable amount of proteolytic activity in the effusions, range 0.05-1.79 micrograms/mg of non-dialysable solids. This proteolytic activity was not significantly different between the thick and thin effusions and was therefore unlikely to explain the difference in viscosity. Analysis of the constituents of the effusions showed that glycoprotein and DNA but not protein nor lipid were significantly higher in the mucoid effusions compared to the serous effusions. The viscosity of the effusions correlated with the glycoprotein concentration but not with the protein or lipid concentration. Under certain circumstances the DNA concentration did correlate with the viscosity of the effusion. However, digestion with a proteinase free DNase did not reduce the viscosity of the effusion. These results demonstrate that classifying effusions as thick and thin based on visual inspection and flow properties is valid and that the only constituent present in the effusions that determines viscosity is mucin.

Radiation induced EPR centers in foodstuffs and inorganic materials.

EPR investigations of a variety of irradiated materials have provided the potential for useful dosimetry applications. Herbs and spices imported into Australia have been investigated to establish whether or not they have been irradiated. Post-irradiation studies have shown that there is more than one free radical species in most cases which decay rapidly with time. Changes to transition metal ion signals, e.g., Cu2+ or Fe3+, appear to be permanent against further irradiation. Thus if these signals change upon irradiation, the material almost certainly has not previously been irradiated. Power saturation studies of alanine, a favored dosimetry material, suggest two distinguishable types of behavior consistent with the presence of spin-flip transitions. Irradiation of vanadium doped beryl yields stable VO2+ ions which may provide a useful dosimetry material. Dosimetry applications would appear to demand low cost, user friendly, automated EPR spectrometers. A patented option based on a 2.5 GHz microstrip microwave bridge will be described briefly.