Implementation costs of the appraise alcohol brief intervention (ABI) for male remand prisoners: A micro-costing protocol and preliminary findings.

OBJECTIVE: This paper documents the methods used to assess the implementation costs of the APPRAISE alcohol brief intervention (ABI) delivered to male remand prisoners across two study sites in Scotland and North East England. METHOD: We first developed a comprehensive taxonomy of the activities constituting the APPRIASE ABI. Next, data were collected for each activity about the study staff and the subject time spent, in addition to the other resources used and unit costs. RESULTS: From the pilot data collection it was possible to construct a narrative, for both study sites, for how the intervention was delivered and the time required for each activity. The ABI was delivered by Change Grow Live and Humankind intervention staff and staff salaries were obtained from both organizations to calculate the staff delivery costs for each site. Other costs, such as the printing of materials, were estimated based on APPRAISE study records. Due to the ongoing Covid-19 restrictions and limited access to prison resources and staff, there were significant deviations from the initial study protocols. As a result, we document the costs of implementing the ABI as delivered rather than as planned. CONCLUSIONS: This paper provides the first estimates of the implementation costs of an ABI delivered in criminal justice setting in the UK. Although these costs are from a pilot implementation that was heavily impacted by the Covid-19 pandemic, this paper nonetheless provides useful, policy-relevant information on the potential costs of providing ABI to remand prisoners. It also serves as a methodological template, guidance, and proof of concept for future micro-costing studies of ABIs in criminal justice settings.

The experiences of men in prison who do not receive visits from family or friends: A qualitative systematic review.

BACKGROUND: Visits present an opportunity for prisoners to preserve family ties and reduce isolation, but not all receive visits from family or friends whilst incarcerated. AIMS: To locate, appraise and synthesise qualitative data on the experiences of adult male prisoners (aged 18 years+) who do not receive prison visits from family or friends. METHODS: Nine electronic databases were searched from the date of their inception until March 2023. The quality of included studies was assessed using the Critical Appraisal Skills Programme checklist for qualitative studies, and data from the studies were synthesised using the thematic synthesis method. RESULTS: Eighteen studies from seven countries (the USA, the UK [England, Northern Ireland & Scotland], Canada, Netherlands and the Philippines) were eligible for inclusion. Three main themes emerged: (1) reasons for not receiving visits, (2) harmful effects of not receiving visits and (3) the value of volunteer visitor programmes. Practical problems were cited as interfering with visiting opportunities, but also some prisoners or families chose not to meet in prison. Loneliness and depression were extensively described as effects of not receiving visits. Qualities associated with volunteer visitors included raised self-esteem, improved mood and personal growth. CONCLUSION: Narratives of the experiences of adult men in prison without visits from family or friends suggest that not only the practical difficulties of imprisonment affect visiting; barriers that prisoners themselves impose would merit further exploration, as would family and relationship dynamics during incarceration and the emotional impact of prison visits, for both prisoners and their families. There are suggestions of therapeutic as well as humanitarian benefits from volunteer visiting programmes. There is a gap in the literature about any specific effect on rebuilding family relationships.

Studying the concentration of polymers in blended microplastics using 2D and 3D Raman mapping.

The combination of different polymers in the form of blended plastics has been used in the plastic industry for a long time. Nevertheless, analyses of microplastics (MPs) have been mainly limited to the study of particles made of single-type polymers. Accordingly, two members of the Polyolefins (POs) family, i.e., Polypropylene (PP) and Low-density Polyethylene (LDPE) are blended and extensively studied in this work due to their applications in industry as well as abundance in the environment. It is shown that 2-D Raman mapping only provides information about the surface of blended MPs (B-MPs). While complimentary 3-D volume analysis is needed to fully understand the presence of various polymers in such complex samples. Therefore, 3-D Raman mapping is applied to visualize the morphology of the distribution of polymers within the B-MPs together with the quantitative estimation of their concentrations. A parameter defined as the concentration estimate error (CEE) evaluates the precision of the quantitative analysis. Furthermore, the impact of four excitation wavelengths 405, 532, 633, and 785 nm is investigated on the obtained results. Finally, the application of a line-shaped laser beam profile (line-focus) is introduced for reducing the measurement time from 56 to 2 h.

A multicomponent psychosocial intervention to reduce substance use by adolescents involved in the criminal justice system: the RISKIT-CJS RCT.

Background: Substance use and offending are related in the context of other disinhibitory behaviours. Adolescents involved in the criminal justice system constitute a particularly vulnerable group, with a propensity to engage in risky behaviour that has long-term impact on their future health and well-being. Previous research of the RISKIT programme provided evidence of a potential effect in reducing substance use and risky behaviour in adolescents. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of a multicomponent psychosocial intervention compared with treatment as usual in reducing substance use for substance-using adolescents involved in the criminal justice system. Design: A mixed-methods, prospective, pragmatic, two-arm, randomised controlled trial with follow-up at 6 and 12 months post randomisation. Setting: The study was conducted across youth offending teams, pupil referral units and substance misuse teams across four areas of England (i.e. South East, London, North West, North East). Participants: Adolescents aged between 13 and 17 years (inclusive), recruited between September 2017 and June 2020. Interventions: Participants were randomised to treatment as usual or to treatment as usual in addition to the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme was a multicomponent intervention and consisted of two individual motivational interviews with a trained youth worker (lasting 45 minutes each) and two group sessions delivered over half a day on consecutive weeks. Main outcome measures: At 12 months, we assessed per cent days abstinent from substance use over the previous 28 days. Secondary outcome measures included well-being, motivational state, situational confidence, quality of life, resource use and fidelity of interventions delivered. Results: A total of 693 adolescents were assessed for eligibility, of whom 505 (73%) consented. Of these, 246 (49%) were allocated to the RISKIT-CJS intervention and 259 (51%) were allocated to treatment as usual only. At month 12, the overall follow-up rate was 57%: 55% in the RISKIT-CJS arm and 59% in the treatment-as-usual arm. At month 12, we observed an increase in per cent days abstinent from substances in both arms of the study, from 61% to 85%, but there was no evidence that the RISKIT-CJS intervention was superior to treatment as usual. A similar pattern was observed for secondary outcomes. The RISKIT-CJS intervention was not found to be any more cost-effective than treatment as usual. The qualitative research indicated that young people were positive about learning new skills and acquiring new knowledge. Although stakeholders considered the intervention worthwhile, they expressed concern that it came too late for the target population. Limitations: Our original aim to collect data on offences was thwarted by the onset of the COVID-19 pandemic, and this affected both the statistical and economic analyses. Although 214 (87%) of the 246 participants allocated to the RISKIT-CJS intervention attended at least one individual face-to-face session, 98 (40%) attended a group session and only 47 (19%) attended all elements of the intervention. Conclusions: The RISKIT-CJS intervention was no more clinically effective or cost-effective than treatment as usual in reducing substance use among adolescents involved in the criminal justice system. Future research: The RISKIT-CJS intervention was considered more acceptable, and adherence was higher, in pupil referral units and substance misuse teams than in youth offending teams. Stakeholders in youth offending teams thought that the intervention was too late in the trajectory for their population. Trial registration: This trial is registered as ISRCTN77037777. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

We explored how useful a psychological intervention was in reducing substance use among young people who had some involvement in the criminal justice system. We recruited young people aged between 13 and 17 years in four areas of England (i.e. South East, London, North West and North East). Young people were recruited from youth offending teams, pupil referral units and substance misuse teams. Those young people who were willing to participate were offered usual treatment and half, chosen at random, were offered an opportunity to take part in the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme had four distinct parts. The first was a 1-hour session that used an approach called motivational interviewing to explore the young person's substance use and discuss different strategies to change their behaviour. This was followed by two group sessions delivered over 2 consecutive weeks. These group sessions addressed risks associated with substance use, what triggers use and the health and social consequences. In addition, young people were taught new skills to help them manage in situations in which they might normally use substances. At the end of the group sessions, the young people had another motivational interview. Twelve months after participants started, we found that the frequency of substance use had decreased in both groups; however, the RISKIT-CJS intervention was no better than treatment as usual. When we spoke with young people who had taken part and staff involved with this population, we got a mixed picture. In some settings, particularly pupil referral units, the RISKIT-CJS intervention was well received by young people and staff, and staff felt that it was a useful additional resource to the work that they were currently undertaking. On the other hand, in the youth offending teams, the staff thought that the programme was too different from their normal work to be implemented easily and they considered the population they work with too established in their substance use and criminal activity to benefit from the programme.

The barriers and facilitators to the reporting and recording of self-harm in young people aged 18 and under: a systematic review.

BACKGROUND AND AIMS: This systematic review sought to identify, explain and interpret the prominent or recurring themes relating to the barriers and facilitators of reporting and recording of self-harm in young people across different settings, such as the healthcare setting, schools and the criminal justice setting. METHODS: A search strategy was developed to ensure all relevant literature around the reporting and recording of self-harm in young people was obtained. Literature searches were conducted in six databases and a grey literature search of policy documents and relevant material was also conducted. Due to the range of available literature, both quantitative and qualitative methodologies were considered for inclusion. RESULTS: Following the completion of the literature searches and sifting, nineteen papers were eligible for inclusion. Facilitators to reporting self-harm across the different settings were found to be recognising self-harm behaviours, using passive screening, training and experience, positive communication, and safe, private information sharing. Barriers to reporting self-harm included confidentiality concerns, negative perceptions of young people, communication difficulties, stigma, staff lacking knowledge around self-harm, and a lack of time, money and resources. Facilitators to recording self-harm across the different settings included being open to discussing what is recorded, services working together and co-ordinated help. Barriers to recording self-harm were mainly around stigma, the information being recorded and the ability of staff being able to do so, and their length of professional experience. CONCLUSION: Following the review of the current evidence, it was apparent that there was still progress to be made to improve the reporting and recording of self-harm in young people, across the different settings. Future work should concentrate on better understanding the facilitators, whilst aiming to ameliorate the barriers.

Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.

Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we reveal FGFR signalling partners proximal to recycling endosomes by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphorylated peptides enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncover that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the recycling endosomes, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve cellular signalling.

A Rapid Systematic Review of Worldwide Alcohol Use Disorders and Brief Alcohol Interventions in the Criminal Justice System.

Although the relationship is complex, there is an association between alcohol use and offending behavior with an interplay between the amount drank, the pattern of drinking and individual and contextual factors. Alcohol brief interventions have been shown to be effective in primary healthcare, however there is currently a lack of compelling evidence in the criminal justice system. We carried out a rapid systematic review of the literature, which updated our review conducted in 2016. Following systematic searches, we included 36 papers on prevalence and 13 papers on effectiveness. Between 26 and 88% of individuals in the policy custody setting scored positive for an alcohol use disorder. In the magistrates court this was 95%; 31-86% in the probation setting and between 19 and 86% in the prison system. In relation to probable dependence, between 21 and 38% of individuals were shown to have probable alcohol dependence in the police custody suite setting; 39 per cent in the magistrate court system; 17-36% in the probation setting and between 18 and 48% in the prison system. This compares to 6% in the general population. We included 13 studies of effectiveness with differing outcome measures and outcomes. We conclude more studies are needed in the field to develop the current evidence base.

Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached.

Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells. Molecules underlying this cancer adaptation may provide alternative drug targets. Here, we demonstrate that diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, is frequently up-regulated in melanoma, allowing melanoma cells to tolerate excess FA. DGAT1 over-expression alone transforms p53-mutant zebrafish melanocytes and co-operates with oncogenic BRAF or NRAS for more rapid melanoma formation. Antagonism of DGAT1 induces oxidative stress in melanoma cells, which adapt by up-regulating cellular reactive oxygen species defenses. We show that inhibiting both DGAT1 and superoxide dismutase 1 profoundly suppress tumor growth through eliciting intolerable oxidative stress.

Nurses' mental health from early COVID-19 pandemic to vaccination.

AIMS: The influence of the COVID-19 vaccine and the evolution of the pandemic over time on nurses' mental health have not been thoroughly examined. This study aimed to explore the changes in nurses' mental health from the early pandemic to the early vaccination period over a 1-year time span and examine vaccination and coping mechanisms as predictors of nurses' poor mental health and burnout. METHODS: Three cross-sectional surveys were conducted: Early-pandemic (n = 320), pre-vaccination (n = 228), and early-vaccination cohorts (n = 292). FINDINGS: About 72% of nurses in the early-vaccination cohort were fully vaccinated with two doses of mRNA COVID-19 vaccines. There were significant decreases in moderate/severe anxiety and moderate/severe depression for the early-vaccination cohort compared to the other cohorts. In multivariate analyses, vaccination had almost three-fold higher odds of moderate/severe anxiety (Odds Ratio [OR] = 2.87; 95% Confidence Interval [CI] = 1.28-6.44). High resilience, family functioning, and spirituality were associated with two- to five-fold lower odds of poor mental health and burnout. CONCLUSIONS: Although nurses in the early-vaccination cohort had lower anxiety and depression than earlier cohorts, COVID-19 vaccination had minimal associations with nurses' mental health. Coping mechanisms and organizational support appear to be important predictors of nurses' poor mental health and burnout. CLINICAL RELEVANCE: The evidence gathered over 1 year of the pandemic may be helpful for a better understanding of the challenges facing frontline nurses and preparing for future healthcare crises. As a part of the preparedness plan for the future, evidence-based interventions that raise frontline nurses' resilience, as well as family and spiritual support, should be considered.

Severe Burnout and Poor Mental Health Among Healthcare Workers 6 Months After COVID-19 Pandemic Declaration: What Can We Learn for Future Emergencies?

OBJECTIVES: The aim of this study was to examine the predictors associated with severe burnout and poor mental health among healthcare workers during the COVID-19 pandemic as a learning opportunity for future emergent situations. BACKGROUND: Modifiable predictors of mental health need to be further examined and quantified to prioritize human resource support in organizations as healthcare workers confront stressful situations. METHODS: A cross-sectional survey was conducted among 271 healthcare workers from September 8 to October 10, 2020. RESULTS: Approximately one-third reported severe burnout, as well as moderate/severe anxiety and depression. Feeling protected working with COVID-19 patients, high family functioning, and spirituality were associated with 2- to 4-fold lower odds of severe burnout. Satisfaction with the organization's communications predicted 2-fold lower odds of anxiety, whereas high resilience was associated with almost 4-fold lower odds of stress and depression. CONCLUSIONS: Healthcare organizations may consider adopting programs to foster resilience, family and spiritual support, and effective communication strategies to reduce burnout and poor mental health among healthcare workers during pandemics and other situations of high stress.

Reciprocal priming between receptor tyrosine kinases at recycling endosomes orchestrates cellular signalling outputs.

Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine-tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling-dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR-mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGF-mediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers.

Engaging smokers in research: Utility of Facebook in facilitating recruitment to a smoking cessation study.

INTRODUCTION: Social media, including Facebook outreach, is increasingly being used as a participant recruitment tool, and may be particularly useful in tobacco and smoking cessation studies. The Recruitment Innovation Center at Vanderbilt University Medical Center partnered with Project LUNA, a smoking cessation study, to conduct a pilot social media campaign aimed at increasing study recruitment. METHODS: Two posts encouraging study participation were developed and promoted on Facebook to users with an interest in smoking-related topics, with a link to a study-specific webpage. Facebook and website analytics were collected, including impressions, clicks, click-through rates, website traffic, and clicks to the study screening form. Study screening and enrollment data were also collected. RESULTS: The Facebook campaign ran in June 2019 in the greater Houston area. In total, the Facebook posts logged 1,179,844 impressions, 6490 clicks, and an overall click-through rate of 0.55%. There were no differences in response to the two different promotional posts. Approximately 3812 unique individuals visited an intermediary study page, with 473 expressing interest in the study. Forty-three potential participants contacted the study team, resulting in study enrollment and randomization of 23 participants, with an estimated cost per enrolled participant of $441. CONCLUSIONS: The social media campaign was successful at increasing outreach and interest in the LUNA study. However, the price-per-participant enrolled was higher than in comparable tobacco cessation studies. These results and lessons learned may be beneficial to others considering social media as a recruitment method for their clinical research trial.

A two-arm parallel-group individually randomised prison pilot study of a male remand alcohol intervention for self-efficacy enhancement: the APPRAISE study protocol.

INTRODUCTION: The prevalence of at-risk drinking is far higher among those in contact with the criminal justice system (73%) than the general population (35%). However, there is little evidence on the effectiveness of alcohol brief interventions (ABIs) in reducing risky drinking among those in the criminal justice system, including the prison system and, in particular, those on remand. Building on earlier work, A two-arm parallel group individually randomised Prison Pilot study of a male Remand Alcohol Intervention for Self-efficacy Enhancement (APPRAISE) is a pilot study designed to assess the feasibility and acceptability of an ABI, delivered to male prisoners on remand. The findings of APPRAISE should provide the information required to design a future definitive randomised controlled trial (RCT). METHODS AND ANALYSIS: APPRAISE will use mixed methods, with two linked phases, across two prisons in the UK, recruiting 180 adult men on remand: 90 from Scotland and 90 from England. Phase I will involve a two-arm, parallel-group, individually randomised pilot study. The pilot evaluation will provide data on the likely impact of A two-arm parallel group individually randomised Prison Pilot study of a male Remand Alcohol Intervention for Self-efficacy Enhancement (APPRAISE), which will be used to inform a future definitive multicentre RCT. Phase II will be a process evaluation assessing how the ABI has been implemented to explore the change mechanisms underpinning the ABI (figure 1) and to assess the context within which the ABI is delivered. ETHICS AND DISSEMINATION: The APPRAISE protocol has been approved by the East of Scotland Research Ethics Committee (19/ES/0068), National Offender Management System (2019-240), Health Board Research and Development (2019/0268), Scottish Prison Service research and ethics committee, and by the University of Edinburgh's internal ethics department. The findings will be disseminated via peer-reviewed journal publications, presentations at local, national and international conferences, infographics and shared with relevant stakeholders through meetings and events. TRIAL REGISTRATION NUMBER: ISRCTN27417180.

Industry Funding and Cholesterol Research: A Systematic Review.

The effect of diet on blood cholesterol concentrations has become controversial. We assessed whether industry-funded studies were more likely than non-industry-funded studies to report conclusions that were not supported by their objective findings. PubMed and Cochrane Central Register of Controlled Trials searches through March 8, 2019, yielded 211 relevant articles. The percentage of industry-funded studies increased from 0% in the 1950s to 60% for 2010 tp 2019 (P < .001). Of 94 non-industry-funded intervention studies for which the effect of egg ingestion on cholesterol concentrations could be determined, net cholesterol increases were reported in 88 (93%) studies (51% statistically significant, 21% not significant, 21% significance not reported). Among 59 industry-funded intervention studies, net cholesterol increases were reported in 51 (86%) studies (34% statistically significant, 39% not significant, and 14% significance not reported). No studies reported significant cholesterol decreases. Nonsignificant net cholesterol decreases were reported by 6 (6%) non-industry-funded and 8 (14%) industry-funded studies. However, 49% of industry-funded intervention studies reported conclusions that were discordant with study results (ie, net cholesterol increases were described as favorable in the articles' stated conclusions), compared with 13% of non-industry-funded studies. Readers, editors, and the public should remain alert to funding sources in interpreting study findings and conclusions.

Osteoblasts contribute to a protective niche that supports melanoma cell proliferation and survival.

Melanoma is the deadliest form of skin cancer; a primary driver of this high level of morbidity is the propensity of melanoma cells to metastasize. When malignant tumours develop distant metastatic lesions the new local tissue niche is known to impact on the biology of the cancer cells. However, little is known about how different metastatic tissue sites impact on frontline targeted therapies. Intriguingly, melanoma bone lesions have significantly lower response to BRAF or MEK inhibitor therapies. Here, we have investigated how the cellular niche of the bone can support melanoma cells by stimulating growth and survival via paracrine signalling between osteoblasts and cancer cells. Melanoma cells can enhance the differentiation of osteoblasts leading to increased production of secreted ligands, including RANKL. Differentiated osteoblasts in turn can support melanoma cell proliferation and survival via the secretion of RANKL that elevates the levels of the transcription factor MITF, even in the presence of BRAF inhibitor. By blocking RANKL signalling, either via neutralizing antibodies, genetic alterations or the RANKL receptor inhibitor SPD304, the survival advantage provided by osteoblasts could be overcome.

A Randomized Controlled Trial in the Evaluation of a Novel Stress Management Tool: A Lounge Chair Experience.

OBJECTIVES: The aim of this study was to compare the stress reduction effects of spending 25 minutes reclining in a SolTec™ Lounge between 2 intervention groups. Group 1 experienced the Lounge with multilayered music on an external speaker, while group 2 experienced the Lounge with multilayered music and synchronous vibration and magnetic stimulation from within the chair. SUBJECTS: In total, 110 participants with a self-reported stress level of 4 or higher on a 0- to 10-point scale were recruited from the local community including employees. Participants were randomized into receiving 1 of the 2 interventions. There were no significant differences between the group's average stress levels prior to the interventions. INTERVENTIONS: Both groups received a 25-minute session in a dimly lit, quiet area on the Lounge with multilayered music. The second group also received vibration and magnetic stimulation that were synchronized with the music. DESIGN: Current stress level as well as ratings or feelings of anxiety, tenseness, energy, focus, happiness, relaxation, nervousness, creativeness, and being rested were recorded before and after the session. RESULTS: Both groups of participants reported equivalent decreased feelings of stress after using the Lounge. Participants receiving the synchronous multilayered music, vibration, and magnetic stimulation did report significantly reduced feelings of tenseness, feeling more relaxed, and feeling more creative when compared with the group that received music only. CONCLUSION: Spending 25 minutes in the SolTec™ Lounge with multilayered music is an effective way to reduce self-reported stress in individuals who self-report having a high stress level. If confirmed by future studies, including synchronous vibration and magnetic stimulation with the multilayered music might be an effective stress reduction strategy.

A PAX3/BRN2 rheostat controls the dynamics of BRAF mediated MITF regulation in MITFhigh /AXLlow melanoma.

The BRAF kinase and the MAPK pathway are targets of current melanoma therapies. However, MAPK pathway inhibition results in dynamic changes of downstream targets that can counteract inhibitor-action not only in during treatment, but also in acquired resistant tumours. One such dynamic change involves the expression of the transcription factor MITF, a crucial regulator of cell survival and proliferation in untreated as well as drug-addicted acquired resistant melanoma. Tight control over MITF expression levels is required for optimal melanoma growth, and while it is well established that the MAPK pathway regulates MITF expression, the actual mechanism is insufficiently understood. We reveal here, how BRAF through action on the transcription factors BRN2 and PAX3 executes control over the regulation of MITF expression in a manner that allows for considerable plasticity. This plasticity provides robustness to the BRAF mediated MITF regulation and explains the dynamics in MITF expression that are observed in patients in response to MAPK inhibitor therapy.

A Systematic Review of the Efficacy of Alcohol Interventions for Incarcerated People.

AIM: The aim of this current study was to systematically review the literature on brief alcohol interventions for incarcerated individuals to ascertain the efficacy or effectiveness in making changes to either consumption of alcohol or other social outcomes. SHORT SUMMARY: Levels of risky drinking and dependency are high amongst incarcerated individuals. Eleven studies from nine articles were included in the systematic review. Six of the studies included brief intervention and three extended interventions. Interventions have the potential to positively impact on risky drinking. More studies are needed in this setting. INTRODUCTION: It has been shown that around three times as many incarcerated individuals are risky drinkers and alcohol dependency is ten times higher than in the general population. METHODS: Systematic review of randomised controlled trials or matched group trials of the efficacy of psychosocial alcohol interventions for incarcerated individuals: we searched seven databases, with no restrictions on language, year or location from inception through to August 2017. The Critical Appraisal Skills Programme tool was used to assess the quality of included studies. The Template for Intervention Description and Replication checklist was used to ascertain intervention descriptions. RESULTS: Nine studies from 11 papers were included in the analysis. Six of the studies included brief interventions and three extended interventions. Every study used a different measure of alcohol consumption. Three of the studies that looked at brief interventions and all of the three extended intervention studies found significant reductions in relation to alcohol outcomes. CONCLUSIONS: Results show that interventions in the prison setting have the potential to positively impact on alcohol use; however, because of small numbers and the use of different outcome measures we could not conduct a meta-analysis or generalise findings. Future studies are needed to standardise approaches to ensure greater rigour and efficacy.