Structure and Function in Homodimeric Enzymes:Simulations of Cooperative and Independent Functional Motions

Large-scale conformational change is a common feature in the catalytic cycles of enzymes. Many enzymes function as homodimers with active sites that contain elements from both chains. Symmetric and anti-symmetric cooperative motions in homodimers can potentially lead to correlated active site opening and/or closure, likely to be important for ligand binding and release. Here, we examine such motions in two different domain-swapped homodimeric enzymes: the DcpS scavenger decapping enzyme and citrate synthase. We use and compare two types of all-atom simulations: conventional molecular dynamics simulations to identify physically meaningful conformational ensembles, and rapid geometric simulations of flexible motion, biased along normal mode directions, to identify relevant motions encoded in the protein structure. The results indicate that the opening/closure motions are intrinsic features of both unliganded enzymes. In DcpS, conformational change is dominated by an anti-symmetric cooperative motion, causing one active site to close as the other opens; however a symmetric motion is also significant. In CS, we identify that both symmetric (suggested by crystallography) and asymmetric motions are features of the protein structure, and as a result the behaviour in solution is largely non-cooperative. The agreement between two modelling approaches using very different levels of theory indicates that the behaviours are indeed intrinsic to the protein structures. Geometric simulations correctly identify and explore large amplitudes of motion, while molecular dynamics simulations indicate the ranges of motion that are energetically feasible. Together, the simulation approaches are able to reveal unexpected functionally relevant motions, and highlight differences between enzymes

Facilitating access to health research through a participatory research register:a feasibility study in outpatient clinics

Abstract Background A research register (Reach West) has been established to facilitate recruitment of people and patients to health-related research. We conducted a prospective feasibility study to investigate the practicality of recruiting through outpatient clinics. Methods Patients over 18 years of age attending dental, eye or oncology outpatient clinics in an acute hospital in the West of England were provided with the opportunity to participate in Reach West. In Phase I, recruitment packs were handed to clinic attendees who could place completed consent forms in secure drop-box or return them later on-line or by post. In Phase II, recruitment packs were posted directly to patients with consent forms to be returned by post or on-line. Response rates by age, sex, postcode (for level of deprivation), and clinic type were recorded for those agreeing to participate on paper or on-line. Results In Phase I, 2,314 of 4,500 (51.4%) of recruitment packs were handed out to clinic attendees, and 114 (5%) consented to join Reach West. In Phase II, 7,173 of 9000 packs were posted (79.7%), and 387 (5.4%) consented to participate. The overall consent rate was 6% (580), with the majority doing so on paper (87%) rather than on-line. The sample was balanced by sex, but mostly comprised people over 50 years located in less deprived postcodes. Non-staff costs for postal recruitment were lower than hand-outs in clinic (£6.84 compared with £8.05 per participant). Conclusions Recruiting participants to the Reach West register was feasible among those with oncology, dental or eye outpatient appointments by post or with packs given out in the clinic. Response rates were similar to those achieved for other registers. Recruitment of participants can be achieved through outpatient clinics but other strategies will also be required to attract large numbers of participants and more diverse populations

The provision of dietary and physical activity advice for men diagnosed with prostate cancer:a qualitative study of the experiences and views of health care professionals, patients and partners

PURPOSE: To explore the views and experiences of health care professionals (HCPs), men diagnosed with localised prostate cancer and their partners about the provision of advice on diet and physical activity after diagnosis and treatment for localised prostate cancer. METHODS: Semi-structured in-depth interviews with ten HCPs (Consultant Urological Surgeons, Uro-Oncology Clinical Nurse Specialists and Allied Health Professionals: see Table 1) and sixteen men diagnosed with localised prostate cancer and seven of their partners. Data from interviews were thematically analysed using the Framework Approach. RESULTS: The men and their partners provided differing accounts to the HCPs and sometimes to each other concerning the provision of advice on diet and physical activity. Some men were unable to recall receiving such advice from HCPs. Factors impacting upon advice-giving included the perceived lack of an evidence base to support dietary and physical activity advice and the credibility of advice providers. The timing of advice provision was a contentious issue as some HCPs believed that patients might not be willing to receive dietary and physical activity advice at the time of diagnosis, whilst others viewed this an opportune time to provide behaviour change information. Patients concurred with the latter opinion. CONCLUSIONS: Men and their partners would value nutritional and physical activity advice from their HCP, after a localised prostate cancer diagnosis. Men would prefer to receive this advice at an early stage in their cancer journey and may implement behaviour change if the received advice is clear and evidence-based. HCPs should receive suitable training regarding what information to provide to men and how best to deliver this information

Facilitating access to health research through a participatory research register:a feasibility study in outpatient clinics

Abstract Background A research register (Reach West) has been established to facilitate recruitment of people and patients to health-related research. We conducted a prospective feasibility study to investigate the practicality of recruiting through outpatient clinics. Methods Patients over 18 years of age attending dental, eye or oncology outpatient clinics in an acute hospital in the West of England were provided with the opportunity to participate in Reach West. In Phase I, recruitment packs were handed to clinic attendees who could place completed consent forms in secure drop-box or return them later on-line or by post. In Phase II, recruitment packs were posted directly to patients with consent forms to be returned by post or on-line. Response rates by age, sex, postcode (for level of deprivation), and clinic type were recorded for those agreeing to participate on paper or on-line. Results In Phase I, 2,314 of 4,500 (51.4%) of recruitment packs were handed out to clinic attendees, and 114 (5%) consented to join Reach West. In Phase II, 7,173 of 9000 packs were posted (79.7%), and 387 (5.4%) consented to participate. The overall consent rate was 6% (580), with the majority doing so on paper (87%) rather than on-line. The sample was balanced by sex, but mostly comprised people over 50 years located in less deprived postcodes. Non-staff costs for postal recruitment were lower than hand-outs in clinic (£6.84 compared with £8.05 per participant). Conclusions Recruiting participants to the Reach West register was feasible among those with oncology, dental or eye outpatient appointments by post or with packs given out in the clinic. Response rates were similar to those achieved for other registers. Recruitment of participants can be achieved through outpatient clinics but other strategies will also be required to attract large numbers of participants and more diverse populations

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

Body image issues and attitudes towards exercise amongst men undergoing androgen deprivation therapy (ADT) following diagnosis of prostate cancer

© 2019 John Wiley & Sons, Ltd. Background: Androgen deprivation therapy (ADT) is an established treatment for prostate cancer (PCa), but its side-effects can affect body appearance and functioning. However, research into the impact of ADT on body image is limited. Exercise can help patients to counterbalance some side-effects, potentially improving body image too. However, adherence to exercise recommendations is low. Therefore, we explored body image after ADT and attitudes towards exercise. Methods: Twenty two semi-structured interviews were conducted with PCa patients receiving ADT (Mage = 67.9 years old, SD = 9.99). Results: Participants expressed appearance dissatisfaction focusing on body feminization. Participants exercised to counterbalance ADT side-effects and improve mood. Exercise also helped them to re-establish a sense of control over their body and experience a sense of achievement. However, some men described being worried that their appearance and physical performance would be judged by others, so they often exercised alone or gave up exercise. Time management and fatigue were also identified as exercise barriers. Conclusion: These findings highlight the need to further investigate body image concerns and exercise barriers in PCa patients undergoing ADT. These results could also inform support groups and health care professionals on the topic. However, further research should explore the most effective and acceptable ways to provide support to PCa patients on body image issues

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users

The perceptions and experiences of community nurses and patients towards shared decision-making in the home setting : An integrative review

Aim. To explore patients' and community nurses' perceptions and experiences of shared decision-making in the home. Design. Integrative review. Data Sources. CINAHL, British Nursing Index, Psycinfo, Medline and Social Services Abstracts were searched for qualitative, quantitative and mixed methods papers published between 1 December 2001 and 31 October 2023. Review Methods. A systematic search of electronic databases was undertaken using defined inclusion criteria. The included papers were appraised for quality using the Joanna Briggs Institute critical appraisal checklist for qualitative research. Relevant data were extracted and thematically analysed. Results. Fourteen papers comprising 13 research studies were included. Patients attached great importance to their right to be involved in decision-making and noted feeling valued as a unique individual. Communication and trust between the patient and nurse were perceived as fundamental. However, shared decision-making does not always occur in practice. Nurses described tension in managing patients' involvement in decision-making. Conclusion. The findings demonstrate that although patients and community nurses appreciate participating in shared decision-making within the home, there are obstacles to achieving a collaborative process. This is especially relevant when there are fundamentally different perspectives on the decision being made. More research is needed to gain further understanding of how shared decision-making plays out in practice and to understand the tensions that patients and nurses may experience. Implications for the Profession and/or Patient Care. This paper argues that shared decision-making is more than the development of a relationship where the patient can express their views (though of course, this is important). Shared decision-making requires acknowledgement that the patient has the right to full information and should be empowered to choose between options. Nurses should not assume that shared decision-making in community nursing is easy to facilitate and should recognize the tensions that might exist when true patient choice is enabled. Impact. This paper demonstrates how the idea of shared decision-making needs to be explored in the light of everyday practice so that challenges and barriers can be overcome. In particular, the tensions that arise when patients and nurses do not share the same perspective. This paper speaks to the potential of a gap surrounding shared decision-making in theory and how it plays out in practice. Reporting Method. The reporting of this review was guided by the 2020 guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Page et al., 2021). Patient or Public Contribution. This review was carried out as part of a wider study for which service users have been consulted