A systematic review investigating the behaviour change strategies in interventions to prevent misuse of anabolic steroids.

We examined intervention effectiveness of strategies to prevent image- and performance-enhancing drug use. Comprehensive searches identified 14 interventions that met review inclusion criteria. Interventions were predominantly educational and delivered within school sport settings, but targeted a wide range of mediating factors. Identification of effective components was limited across studies by brief or imprecise descriptions of intervention content, lack of behavioural outcome measures and short-term follow-up times. However, studies with components in addition to information provision may be more promising. Interventions outside of sport settings are required to reflect the transition of this form of substance use to the general population

Identification of Novel Human Damage Response Proteins Targeted through Yeast Orthology

Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74%) of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators

The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research

We present a framework for the study of states of chronic pain and transitions between those states. We capture in the framework the dynamic nature of pain: people live with pain that changes over time. First, we offer definitions of both acute and chronic pain and explore the contextual considerations related to the common use of this temporal dichotomy. Second, we promote the importance of incorporating the impact pain has on a person's life. Finally, we discuss the challenges and opportunities inherent in implementing this common approach. Our goal is to produce a framework for the study of the development, maintenance, and resolution of chronic pain. Whether a single brief event or a constant feature of life, pain interrupts to prioritise protection, interferes with activity, reduces quality of life, and can alter identity.44 Protection is achieved by escape from harm, avoidance of perceived danger, withdrawal for respite and repair, and communication of incapacity and environmental risk; longer-term protection is achieved by learning the cues for pain and injury.53 From this perspective, pain is most usefully considered a need state, fundamentally a motivational drive to protect.49 This approach centres our attention on the consequences of pain for the person in their context, on its duration and its impact

A metabolomics investigation into the effects of HIV protease inhibitors on HPV16 E6 expressing cervical carcinoma cells

Recently, it has been reported that anti-viral drugs, such as indinavir and lopinavir (originally targeted for HIV), also inhibit E6-mediated proteasomal degradation of mutant p53 in E6-transfected C33A cells. In order to understand more about the mode-of-action(s) of these drugs the metabolome of HPV16 E6 expressing cervical carcinoma cell lines was investigated using mass spectrometry (MS)-based metabolic profiling. The metabolite profiling of C33A parent and E6-transfected cells exposed to these two antiviral drugs was performed by ultra performance liquid chromatography (UPLC)-MS and gas chromatography (GC)-time of flight (TOF)-MS. Using a combination of univariate and multivariate analyses, these metabolic profiles were investigated for analytical and biological reproducibility and to discover key metabolite differences elicited during anti-viral drug challenge. This approach revealed both distinct and common effects of these two drugs on the metabolome of two different cell lines. Finally, intracellular drug levels were quantified, which suggested in the case of lopinavir that increased activity of membrane transporters may contribute to the drug sensitivity of HPV infected cells

A rapid narrative review of literature on gendered alcohol marketing and its effects: exploring the targeting and representation of women.

This report presents findings of a rapid narrative literature review exploring the gendered nature of alcohol marketing and its effects, focussing specifically on the ways in which women are both targeted and represented, and the implications for drinking practices and gender equity. Overall, the review found that although research has explored the nature of such marketing, there is a lack of research exploring its effects, both in terms of its impact on women’s drinking practices, and how women are viewed and treated in society. Whilst little research has specifically explored how female-targeted marketing affects women’s drinking behaviours, literature has discussed how women in both westernised and lower and middle income countries (LMIC) are targeted by the alcohol industry through a number of strategies. This includes the creation of new products, the use of lifestyle messages that are underpinned by gender stereotypes (e.g. slimness/weight, pink, all-female friendships), offers of stereotypical feminine accessories (e.g. makeup) and messages of empowerment. Interactive techniques (e.g. competitions, photograph requests) on social media are also being used to involve the public, including women, in content creation and to encourage interaction with and the sharing of brand content on social media platforms, in ways that are gendered, and in ways that create a wider audience reach. Concern surrounds the regulation of social media marketing, including in the UK, and whether codes that aim to regulate marketing content are sufficient in regulating marketing that predominantly aims to instigate user interaction, and the co-creation of content. With regards to the way women themselves are depicted in alcohol marketing, research suggests that the gender roles ascribed to women have changed over time, yet new representations of women as sexually active and empowered co-exist alongside their sexualisation and objectification. There is a lack of research exploring perceptions of such marketing and how it influences purchases and drinking practices, but the research that has been undertaken has produced conflicting results. Some suggests that women dislike the use of sexual images of women, including both passive and active depictions, compared to men, yet other research suggests women find sexualised imagery appealing when it is aligned with connotations of empowerment through sexual agency. Further research is needed to better understand the effects of such messaging. Much discussion surrounds the sexualisation of the night time environment (NTE) and its marketing. Despite nightlife venues attempting to become more ‘female-friendly’ through targeting women as potential consumers, the marketing of such spaces reinforces traditional gender relations and the inequalities at play in the NTE, and wider society (e.g. sexualisation and objectification). Recent work highlights the use of women’s bodies and sexualities, including photographs of female patrons, to promote nightlife venues on social media in a way that reproduces the male gaze. In light of such findings, concern surrounds the implications of both brand and NTE marketing content that normalises the objectification and sexualisation of women on attitudes towards, and the treatment of women, within society (i.e. unwanted sexual attention, male entitlement to women’s bodies, ‘rape culture’). Little research has explored the actual effects of brand and NTE marketing of this nature, and it is important that future research explores its impact on women’s lived experiences. There is also evidence that brand and NTE marketing can breach self-regulatory codes, particularly those surrounding sex, sexual success and attractiveness, thus raising questions surrounding the effectiveness of these regulatory systems. A number of gaps in research are outlined that require further investigation to allow for a better understanding of the effects of female targeted marketing on women’s drinking experiences, and the effects of marketing that uses women’s bodies and sexualities on gender equity. Based on the findings and the suggestions for policy change discussed within the included studies, a number of recommendations for policy and practice in the United Kingdom (UK) are outlined

Opioid prescribing and social deprivation: A retrospective analysis of prescribing for CNCP in Liverpool CCG.

BackgroundTreating Chronic Non-Cancer Pain (CNCP) with long-term, high dose and more potent opioids puts patients at increased risk of harm, whilst providing limited pain relief. Socially deprived areas mapped from Index of Multiple Deprivation (IMD) scores show higher rates of high dose, strong opioid prescribing compared to more affluent areas.ObjectiveTo explore if opioid prescribing is higher in more deprived areas of Liverpool (UK) and assess the incidence of high dose prescribing to improve clinical pathways for opioid weaning.Design and settingThis retrospective observational study used primary care practice and patient level opioid prescribing data for N = 30,474 CNCP patients across Liverpool Clinical Commissioning Group (LCCG) between August 2016 and August 2018.MethodA Defined Daily Dose (DDD) was calculated for each patient prescribed opioids. DDD was converted into a Morphine Equivalent Dose (MED) and patients stratified according to high (≥120mg) MED cut off. The association between prescribing and deprivation was analysed by linking GP practice codes and IMD scores across LCCG.Results3.5% of patients were prescribed an average dose above 120mg MED/day. Patients prescribed long-term, high dose, strong opioids were more likely to be female, aged 60+, prescribed three opioids and reside in the North of Liverpool where there is a higher density of areas in the IMD most deprived deciles.ConclusionA small but significant proportion of CNCP patients across Liverpool are currently prescribed opioids above the recommended dose threshold of 120mg MED. Identification of fentanyl as a contributor to high dose prescribing resulted in changes to prescribing practice, and reports from NHS pain clinics that fewer patients require tapering from fentanyl. In conclusion, higher rates of high dose opioid prescribing continue to be evident in more socially deprived areas further increasing health inequalities

Exploring the Clinical Usefulness of Undergraduate Medical Research:art

A significant amount of published clinical research has no measurable impact on health and disease outcomes, and research in undergraduate medical education is viewed as especially susceptible. The aims of this mixed methods study were to (a) to use group concept mapping (GCM) to explore key features identified by hospital physicians, medical educators, and medical students as central to clinical usefulness in an undergraduate medical research context, and (b) review a sample of undergraduate medical research projects based on usefulness criteria described by Ioannidis (2016). In the GCM procedure, 54 respondents (39 students, 15 physicians) from an Irish medical school participated across each of three phases: brainstorming, sorting, and rating. Data was analysed using multidimensional scaling and hierarchical clustering. A retrospective analysis of 252 student projects was also completed using a rubric based on Ioannidis’s (2016) six domains of “clinical usefulness”: problem base, context placement and information gain, pragmatism, patient-centredness, feasibility, and transparency. Projects were scored for each domain by three assessors. Results were analysed and presented using descriptive analysis.GCM analysis revealed the following “clinically useful” research characteristics: optimal design and methodology, practicality, research skills development, translational impact, patient-centredness, and asking a clinical question. Following a rubric-based analysis of projects, the highest scoring categories (mean rating; range of 1–4) were feasibility (3.57), transparency (3.32), and problem base (3.05). The lowest scoring areas were context placement and information gain (2.73), pragmatism (2.68), and patient-centredness (212). We identified considerable conceptual overlap between stakeholder consensus views on “clinical usefulness” as applied to undergraduate research and Ioannidis’s criteria. Patient-centredness was identified as a domain requiring greater emphasis during the design of undergraduate medical research.</p

Feasibility study of a Behavioural Intervention for Opioid Reduction (BIOR) for patients with chronic non-cancer pain in primary care: a protocol

IntroductionAround 30%-50% of adults suffer moderate to severe chronic pain not caused by cancer. Significant numbers are treated with opioids which over time may cease to be effective and produce side effects (eg, nausea, drowsiness and constipation). Stopping taking opioids abruptly can cause unpleasant withdrawal effects. Tapering in small steps is recommended, though some patients might struggle and need support, particularly if they have limited access to pain management alternatives. Awareness of the potential risks as well as benefits of tapering should be explored with patients.Methods and analysisA randomised controlled pilot feasibility study to investigate the effectiveness and feasibility of reducing high doses of opioids through a tapering protocol, education and support in primary care. Working with NHS Knowsley Place, we will identify patients taking 50 mg or above morphine equivalent dose of opioids per day to be randomly allocated to either the tapering group or tapering with support group. At an initial joint appointment with a pain consultant and General Practitioner (GP) GP tapering will be discussed and negotiated. Both groups will have their opioid reduced by 10% per week. The taper with support group will have access to additional support, including motivational counselling, realistic goal setting and a toolkit of resources to promote self-management. Some patients will successfully reduce their dose each week. For others, this may be more difficult, and the tapering reduction will be adjusted to 10% per fortnight. We assess opioid use, pain and quality of life in both groups at the start and end of the study to determine which intervention works best to support people with chronic pain who wish to stop taking opioids.Ethics and disseminationThe Behavioural Intervention for Opioid Reduction feasibility study has been granted full approval by Liverpool Central Research Ethics Committee on 7 April 2022 (22/NW/0047). The current protocol version is V.1.1, date 6 July 2022. Results will be published in peer-reviewed journals and disseminated to patient stakeholders in a lay summary report available on the project website and in participating GP surgeries.Trial registration numberISRCTN 30201337