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1.
EMBO J ; 40(14): e107182, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34086370

RESUMO

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.


Assuntos
Endossomos/metabolismo , Transporte Proteico/fisiologia , Transdução de Sinais/fisiologia , Tirosina/metabolismo , Linhagem Celular Tumoral , Endocitose/fisiologia , Receptores ErbB/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Fosforilação/fisiologia
2.
Crim Behav Ment Health ; 34(3): 271-295, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38389175

RESUMO

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.


Assuntos
Família , Amigos , Prisioneiros , Pesquisa Qualitativa , Humanos , Masculino , Prisioneiros/psicologia , Família/psicologia , Adulto , Amigos/psicologia , Solidão/psicologia , Prisões
3.
BMC Public Health ; 23(1): 158, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694149

RESUMO

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.


Assuntos
Comportamento Autodestrutivo , Humanos , Adolescente , Comportamento Autodestrutivo/diagnóstico , Estigma Social , Instituições Acadêmicas
4.
J Nurs Scholarsh ; 54(4): 485-492, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34967492

RESUMO

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.


Assuntos
Esgotamento Profissional , COVID-19 , Enfermeiras e Enfermeiros , Esgotamento Profissional/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Saúde Mental , Pandemias , Vacinação
5.
J Nurs Adm ; 51(11): 554-560, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34690302

RESUMO

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.


Assuntos
Esgotamento Profissional/epidemiologia , Emergências , Pessoal de Saúde/psicologia , Saúde Mental , Ansiedade/psicologia , COVID-19 , Estudos Transversais , Humanos , Estresse Psicológico/psicologia
6.
Alcohol Alcohol ; 53(4): 412-425, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29750413

RESUMO

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.


Assuntos
Consumo de Bebidas Alcoólicas/terapia , Prisioneiros , Psicoterapia , Consumo de Bebidas Alcoólicas/psicologia , Humanos , Prisioneiros/psicologia
7.
Postgrad Med J ; 94(1109): 131-136, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29103016

RESUMO

PURPOSE OF THE STUDY: To examine the use of alcohol and other substances among medical and law students at a UK university. STUDY DESIGN: Anonymous cross-sectional questionnaire survey of first, second and final year medical and law students at a single UK university. RESULTS: 1242 of 1577 (78.8%) eligible students completed the questionnaire. Over half of first and second year medical students (first year 53.1%, second year 59.7%, final year 35.9%) had an Alcohol Use Disorders Identification Test (AUDIT) score suggestive of an alcohol use disorder (AUDIT≥8), compared with over two-thirds of first and second year law students (first year 67.2%, second year 69.5%, final year 47.3%). Approximately one-quarter of medical students (first year 26.4%, second year 28.4%, final year 23.7%) and over one-third of first and second year law students (first year 39.1%, second year 42.4%, final year 18.9%) reported other substance use within the past year. Over one-third of medical students (first year 34.4%, second year 35.6%, final year 46.3%) and approximately half or more of law students (first year 47.2%, second year 52.7%, final year 59.5%) had a Hospital Anxiety and Depression Scale anxiety score suggestive of a possible anxiety disorder. CONCLUSIONS: Study participants had high levels of substance misuse and anxiety. Some students' fitness to practice may be impaired as a result of their substance misuse or symptoms of psychological distress. Further efforts are needed to reduce substance misuse and to improve the mental well-being of students.


Assuntos
Ansiedade/epidemiologia , Advogados , Estresse Psicológico/epidemiologia , Estudantes de Medicina , Transtornos Relacionados ao Uso de Substâncias , Adulto , Ansiedade/diagnóstico , Ansiedade/prevenção & controle , Estudos Transversais , Feminino , Humanos , Advogados/educação , Advogados/psicologia , Advogados/estatística & dados numéricos , Masculino , Saúde Mental/normas , Melhoria de Qualidade , Estresse Psicológico/diagnóstico , Estresse Psicológico/prevenção & controle , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inquéritos e Questionários , Reino Unido/epidemiologia , Universidades/estatística & dados numéricos
9.
J Cell Sci ; 127(Pt 6): 1346-56, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24424027

RESUMO

The target of rapamycin (TOR) kinase regulates cell growth and division. Rapamycin only inhibits a subset of TOR activities. Here we show that in contrast to the mild impact of rapamycin on cell division, blocking the catalytic site of TOR with the Torin1 inhibitor completely arrests growth without cell death in Schizosaccharomyces pombe. A mutation of the Tor2 glycine residue (G2040D) that lies adjacent to the key Torin-interacting tryptophan provides Torin1 resistance, confirming the specificity of Torin1 for TOR. Using this mutation, we show that Torin1 advanced mitotic onset before inducing growth arrest. In contrast to TOR inhibition with rapamycin, regulation by either Wee1 or Cdc25 was sufficient for this Torin1-induced advanced mitosis. Torin1 promoted a Polo and Cdr2 kinase-controlled drop in Wee1 levels. Experiments in human cell lines recapitulated these yeast observations: mammalian TOR (mTOR) was inhibited by Torin1, Wee1 levels declined and mitotic commitment was advanced in HeLa cells. Thus, the regulation of the mitotic inhibitor Wee1 by TOR signalling is a conserved mechanism that helps to couple cell cycle and growth controls.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Mitose/efeitos dos fármacos , Naftiridinas/farmacologia , Proteínas Nucleares/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/crescimento & desenvolvimento , Sequência de Aminoácidos , Domínio Catalítico , Morte Celular , Resistência a Medicamentos , Pontos de Checagem da Fase G1 do Ciclo Celular , Células HeLa , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Dados de Sequência Molecular , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/metabolismo , Mutagênese Sítio-Dirigida , Fosfatidilinositol 3-Quinases/metabolismo , Transporte Proteico , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/enzimologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
10.
J Biol Chem ; 289(42): 29386-96, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25164808

RESUMO

Folylpoly-γ-glutamate synthetase (FPGS) catalyze the addition of multiple glutamates to tetrahydrofolate derivatives. Two mRNAs for the fpgs gene direct isoforms of FPGS to the cytosol and to mitochondria in mouse and human tissues. We sought to clarify the functions of these two compartmentalized isoforms. Stable cell lines were created that express cDNAs for the mitochondrial and cytosolic isoforms of human FPGS under control of a doxycycline-inducible promoter in the AUXB1 cell line. AUXB1 are devoid of endogenous FPGS activity due to a premature translational stop at codon 432 in the fpgs gene. Loss of folates was not measurable from these doxycycline-induced cells or from parental CHO cells over the course of three CHO cell generations. Likewise, there was no detectable transfer of folate polyglutamates either from the cytosol to mitochondria, or from mitochondria to the cytosol. The cell line expressing cytosolic FPGS required exogenous glycine but not thymidine or purine, whereas cells expressing the mitochondrial isoform required exogenous thymidine and purine but not glycine for optimal growth and survival. We concluded that mitochondrial FPGS is required because folate polyglutamates are not substrates for transport across the mitochondrial membrane in either direction and that polyglutamation not only traps folates in the cytosol, but also in the mitochondrial matrix.


Assuntos
Citosol/enzimologia , Ácido Fólico/química , Mitocôndrias/enzimologia , Peptídeo Sintases/metabolismo , Sequência de Aminoácidos , Animais , Transporte Biológico , Células CHO , Cricetinae , Cricetulus , DNA Complementar/metabolismo , Humanos , Membranas Mitocondriais/metabolismo , Dados de Sequência Molecular , Mutação , Isoformas de Proteínas/metabolismo , Homologia de Sequência de Aminoácidos
11.
Curr Neurol Neurosci Rep ; 14(10): 488, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25138026

RESUMO

A new appreciation of the microbiome is changing the way we perceive human health and disease. The holobiontic nature of humans is even etched into our DNA in the form of viral symbionts. Empirical evidence for the presence of endogenous retroviruses (ERVs) in the human genome and their activity in homeostatic and pathologic states has accumulated; however, no causal relationship with human disease has been established to date. In this review, we will focus on the role of endogenous retrovirus-K in neurologic disease. Specifically, we will attempt to reconcile the pathologic contribution of ERVK in disparate neurologic diseases by providing evidence as to inter-individual differences in ERVK genotypes, addressing the molecular regulation of ERVK, and provide detailed examples of ERVK-mediated processes in nervous system diseases.


Assuntos
Retrovirus Endógenos/genética , Doenças do Sistema Nervoso/virologia , Retrovirus Endógenos/fisiologia , Humanos , Doenças do Sistema Nervoso/genética , Fenótipo , Fatores de Transcrição/metabolismo , Transcrição Gênica
12.
Can J Diet Pract Res ; 75(4): 206-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26067075

RESUMO

PURPOSE: To describe and provide recommendations for the implementation of an evaluation for an already existing, in-store Nutrition Label Education Program (NLEP). METHODS: We describe the development and implementation of an evaluation consisting of a pre- and postsurvey and one month follow-up. The evaluation was designed to assess satisfaction with the NLEP as well as changes in participant nutrition label knowledge, confidence in using nutrition labels, and actual changes in nutrition label use. RESULTS: Nineteen participants took part in the pilot evaluation. The evaluation was successful in demonstrating high levels of satisfaction with the NLEP as well as positive changes in participant confidence and some increased knowledge in using nutrition labels. However, only 3 people participated in the follow-up, limiting the ability to assess behaviour change. CONCLUSIONS: Ideally, NLEPs should include ongoing evaluation that extends beyond just assessing participant satisfaction. Recommendations are provided for conducting such evaluations, including the importance of incorporating the evaluation into the program itself, using existing questionnaires when possible, and employing pre- and postsurveys as well as follow-up interviews to assess change.


Assuntos
Informação de Saúde ao Consumidor/métodos , Rotulagem de Alimentos , Política Nutricional , Ciências da Nutrição/educação , Adulto , Idoso , Comportamento do Consumidor , Informação de Saúde ao Consumidor/economia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nova Escócia , Projetos Piloto , Avaliação de Programas e Projetos de Saúde/métodos , Inquéritos e Questionários
13.
J Stud Alcohol Drugs ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669136

RESUMO

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.

14.
Sci Rep ; 13(1): 7771, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173381

RESUMO

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.

15.
Public Health Res (Southampt) ; 11(3): 1-77, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37254608

RESUMO

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.


Assuntos
COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Qualidade de Vida , Estudos Prospectivos , Direito Penal , Pandemias , Intervenção Psicossocial , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Front Psychiatry ; 13: 900186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873244

RESUMO

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.

17.
Nat Commun ; 13(1): 6589, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329028

RESUMO

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.


Assuntos
Endossomos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Ligantes , Endossomos/metabolismo , Endocitose/fisiologia , Autofagia , Fator 10 de Crescimento de Fibroblastos/metabolismo
18.
Cell Rep ; 39(12): 110995, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35732120

RESUMO

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.


Assuntos
Diacilglicerol O-Aciltransferase , Melanoma , Animais , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Proteínas Oncogênicas/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , Triglicerídeos , Peixe-Zebra/metabolismo
19.
Am J Lifestyle Med ; 15(2): 165-172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786032

RESUMO

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.

20.
Contemp Clin Trials ; 107: 106461, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34098038

RESUMO

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.


Assuntos
Abandono do Hábito de Fumar , Mídias Sociais , Humanos , Fumantes , Fumar , Fumar Tabaco
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