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1.
BMC Med Res Methodol ; 22(1): 17, 2022 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-35026996

RESUMEN

BACKGROUND: It is recognised that Black, Asian and Minority Ethnic (BAME) populations are generally underrepresented in research studies. The key objective of this work was to develop an evidence based, practical toolkit to help researchers maximise recruitment of BAME groups in research. METHODS: Development of the toolkit was an iterative process overseen by an expert steering group. Key steps included a detailed literature review, feedback from focus groups (including researchers and BAME community members) and further workshops and communication with participants to review the draft and final versions. RESULTS: Poor recruitment of BAME populations in research is due to complex reasons, these include factors such as inadequate attention to recruitment strategies and planning, poor engagement with communities and individuals due to issues such as cultural competency of researchers, historical poor experience of participating in research, and lack of links with community networks. Other factors include language issues, relevant expertise in research team and a lack of adequate resources that might be required in recruitment of BAME populations. CONCLUSIONS: A toolkit was developed with key sections providing guidance on planning research and ensuring adequate engagement of communities and individuals. Together with sections suggesting how the research team can address training needs and adopt best practice. Researchers highlighted the issue of funding and how best to address BAME recruitment in grant applications, so a section on preparing a grant application was also included. The final toolkit document is practical, and includes examples of best practice and 'top tips' for researchers.


Asunto(s)
Etnicidad , Grupos Minoritarios , Pueblo Asiatico , Grupos Focales , Humanos , Apoyo Social
2.
Nutr Metab Cardiovasc Dis ; 32(6): 1549-1559, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35459607

RESUMEN

BACKGROUND AND AIMS: Structured self-management education has been shown to be effective in type 2 diabetes (T2DM) but more research is needed to look at culturally appropriate programmes in ethnic minority groups, where prevalence of T2DM is higher and diagnosis earlier. The study tested the effectiveness of a group education programme for people with established T2DM in a multi-ethnic primary care population. METHODS AND RESULTS: Cluster randomised trial conducted in two multi-ethnic UK sites. Practices were randomised (1:1) to a structured T2DM group education programme or to continue with routine care. A culturally-adapted version was offered to South Asians, who formed the majority of ethnic minority participants. Other ethnic minority groups were invited to attend the standard programme. Primary outcome was change in HbA1c at 12 months. All analyses accounted for clustering and baseline value.367 participants (64(SD 10.8) years, 36% women, 34% from minority ethnic groups) were recruited from 31 clusters. At 12 months, there was no difference in mean change in HbA1c between the two groups (-0.10%; (95% CI: -0.37, 0.17). Subgroup analyses suggested the intervention was effective at lowering HbA1c in White European compared with ethnic minority groups. The intervention group lost more body weight than the control group (-0.82 kg at 6 months and -1.06 kg at 12 months; both p = 0.03). CONCLUSION: Overall, the programme did not result in HbA1c improvement but in subgroup analysis, a beneficial effect occurred in White Europeans. Findings emphasise a need to develop and evaluate culturally-relevant programmes for ethnic minority groups.


Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Etnicidad , Femenino , Hemoglobina Glucada , Humanos , Masculino , Grupos Minoritarios , Atención Primaria de Salud
3.
J Public Health (Oxf) ; 38(3): 493-501, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26311822

RESUMEN

BACKGROUND: We report development of a group-based lifestyle intervention, Let's Prevent, using the UK Medical Research Council (MRC) framework, and delivered by structured education to prevent type 2 diabetes mellitus (T2DM) in people with impaired glucose regulation (IGR) in a UK multi-ethnic population. METHODS: Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national T2DM programme that meets National Institute for Health and Care Excellence criteria and formed the basis for Let's Prevent. An iterative cycle of initial development, piloting, collecting and collating qualitative and quantitative data, and reflection and modification, was used to inform and refine lifestyle intervention until it was fit for evaluation in a definitive randomized controlled trial (RCT). The programme encouraged IGR self-management using simple, non-technical language and visual aids. RESULTS: Qualitative and quantitative data suggested that intervention resulted in beneficial short-term behaviour change such as healthier eating patterns, improved health beliefs and greater participant motivation and empowerment. We also demonstrated that recruitment strategy and data collection methods were feasible for RCT implementation. CONCLUSIONS: Let's Prevent was developed following successful application of MRC framework criteria and the subsequent RCT will determine whether it is feasible, reliable and transferable from research into a real-world NHS primary healthcare setting. TRIAL REGISTRATION: ISRCTN80605705.


Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Intolerancia a la Glucosa/prevención & control , Promoción de la Salud/métodos , Conducta de Reducción del Riesgo , Anciano , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Automanejo/métodos , Reino Unido
4.
N Engl J Med ; 364(7): 616-26, 2011 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-21323541

RESUMEN

BACKGROUND: Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population. METHODS: We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method). RESULTS: In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A(2) receptor (PLA(2)R1) (SNP rs4664308, P=8.6×10(-29)), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P=8.0×10(-93)). The association with HLA-DQA1 was significant in all three populations (P=1.8×10(-9), P=5.6×10(-27), and P=5.2×10(-36) in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2). CONCLUSIONS: An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA.


Asunto(s)
Estudio de Asociación del Genoma Completo , Glomerulonefritis Membranosa/genética , Antígenos HLA-DQ/genética , Polimorfismo de Nucleótido Simple , Receptores de Fosfolipasa A2/genética , Alelos , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 6 , Europa (Continente) , Femenino , Genotipo , Cadenas alfa de HLA-DQ , Humanos , Masculino , Oportunidad Relativa , Población Blanca/genética
5.
Cancer Res ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356622

RESUMEN

Resistance to endocrine therapies (ET) is common in estrogen receptor (ER) positive breast cancer, and most relapsed patients die with ET-resistant disease. While genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance. By analyzing histone H3 lysine 27 acetylation (H3K27ac) profiles and transcriptional reprogramming in models of ET resistance, we discovered that selective ER degraders (SERDs), such as fulvestrant, promote expression of VGLL1, a co-activator for TEAD transcription factors. VGLL1, acting via TEADs, promoted expression of genes that drive growth of fulvestrant-resistant breast cancer cells. Pharmacological disruption of VGLL1/TEAD4 interaction inhibited VGLL1/TEAD-induced transcriptional programs to prevent growth of resistant cells. EGFR was among the VGLL1/TEAD-regulated genes, and VGLL1-directed EGFR upregulation sensitized fulvestrant-resistant breast cancer cells to EGFR inhibitors. Taken together, these findings identify VGLL1 as a transcriptional driver in ET resistance and advance therapeutic possibilities for relapsed ER+ breast cancer patients.

6.
Blood ; 117(5): 1614-21, 2011 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-21106986

RESUMEN

Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginase to resist proteolytic cleavage and at the same time improve activity. We employed a novel combination of mutant sampling using a genetic algorithm in tandem with flexibility studies using molecular dynamics to investigate the impact of lid-loop and mutations on drug activity. Applying these methods, we successfully predicted the more active L-asparaginase mutants N24T and N24A. For the latter, a unique hydrogen bond network contributes to higher activity. Furthermore, interface mutations controlling secondary glutaminase activity demonstrated the importance of this enzymatic activity for drug cytotoxicity. All selected mutants were expressed, purified, and tested for activity and for their ability to form the active tetrameric form. By introducing the N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized drug design.


Asunto(s)
Asparaginasa/química , Asparaginasa/metabolismo , Proliferación Celular , Glutaminasa/metabolismo , Leucemia/patología , Ingeniería de Proteínas , Asparaginasa/genética , Dominio Catalítico , Simulación por Computador , Glutaminasa/química , Glutaminasa/genética , Humanos , Leucemia/enzimología , Leucemia/genética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Mutación Puntual/genética , Conformación Proteica , Multimerización de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células Tumorales Cultivadas
7.
Prim Care Diabetes ; 17(4): 309-313, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37246032

RESUMEN

AIMS: To implement a diabetes prevention programme in primary care METHODS: The programme was implemented for 12 months in two neighbouring towns, served by eight general practices. Practices requested a referral pathway involving an external administrator running electronic searches and sending postal invitations. If interested, people called and booked a place on the programme. Practices were also provided with resources to refer people directly. Six Educators were trained to deliver the programme. The RE-AIM constructs "Adoption", "Reach" and "Uptake" were assessed. RESULTS: All practices engaged in the searches and postal invitations. Overall, 3.9 % of those aged ≥ 25 years had an HbA1c level indicative of non-diabetic hyperglycaemia (NDH) and were invited. Overall uptake (attended as percentage of invited) was 16 % (practice range 10.5-26.6 %) and was highest in two practices where the invitation was followed by a telephone call. Four people were referred directly by their practice. Groups at risk of being excluded were the Bengali population and those unable to attend because of issues such as health, mobility and frailty. CONCLUSIONS: Comprehensive electronic searches meant everyone previously diagnosed with NDH was invited to attend. Follow-up telephone call improved uptake and providing practices with resources to make these calls themselves would likely increase uptake further.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Inglaterra , Atención Primaria de Salud
8.
Cell Rep Med ; 4(7): 101092, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37348499

RESUMEN

Tertiary lymphoid structure (TLS) is associated with prognosis in copy-number-driven tumors, including high-grade serous ovarian cancer (HGSOC), although the function of TLS and its interaction with copy-number alterations in HGSOC are not fully understood. In the current study, we confirm that TLS-high HGSOC patients show significantly better progression-free survival (PFS). We show that the presence of TLS in HGSOC tumors is associated with B cell maturation and cytotoxic tumor-specific T cell activation and proliferation. In addition, the copy-number loss of IL15 and CXCL10 may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed. Last, a radiomics-based signature is developed to predict the presence of TLS, which independently predicts PFS in both HGSOC patients and immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients. Overall, we reveal that TLS coordinates intratumoral B cell and T cell response to HGSOC tumor, while the cancer genome evolves to counteract TLS formation and function.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Cistadenocarcinoma Seroso , Neoplasias Pulmonares , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Pulmonares/patología , Pronóstico , Tejido Linfoide , Neoplasias Ováricas/patología
9.
EMBO Mol Med ; 13(5): e13366, 2021 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-33709473

RESUMEN

Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival compared to RAD51-Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR-proficient cancers (Myriad HRDscore < 42). Interestingly, overexpression of RAD51 modified expression of immune-regulatory pathways in vitro, while RAD51-High tumours showed exclusion of cytotoxic T cells in situ. Our findings highlight RAD51 expression as a determinant of platinum resistance and suggest possible roles for therapy to overcome immune exclusion in RAD51-High EOC. The qIHC approach is generalizable to other proteins with a continuum instead of discrete/bimodal expression.


Asunto(s)
Neoplasias Ováricas , Platino (Metal) , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Femenino , Humanos , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel , Recombinasa Rad51/genética
10.
Fam Pract ; 26(5): 365-71, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19589884

RESUMEN

BACKGROUND: Currently, body mass index (BMI) is widely used to identify health risk due to overweight or obesity. However, waist circumference is considered by many to be a better indicator of health risk than BMI. The primary health care team are ideally suited to screen for people at high risk of glucose intolerance and increased cardiovascular risk using waist circumference measurement (WCM). OBJECTIVES: To determine the knowledge and attitudes of patients and primary care practitioners concerning WCM, with particular reference to exploring barriers in a multi-ethnic setting. METHODS: A qualitative study using purposive sampling, semi-structured interviews and thematic analysis was conducted. Nine general practices were selected from Leicestershire, UK. The participants were 10 practitioners (four practice nurses, six general practitioners) and 18 patients (six south Asians). RESULTS: Two overarching themes were identified from patient and practitioner interviews: understanding of waist size measurement to assess or monitor risk and attitudes related to perceived barriers and facilitators to waist measurement. A few practitioners felt uncomfortable about carrying out WCM and some perceived that patients might feel embarrassed. Practical barriers raised by professionals included lack of time, extra workload and financial implications. In contrast, patients generally raised few barriers to WCM. Being given an explanation appeared to be what was most important to them. No clear differences emerged when comparing views of patients from different ethnic groups or general practitioners and practice nurses. CONCLUSIONS: This study adds to our understanding of views on WCM in a multi-ethnic setting, highlighting factors for consideration if WCM is to be facilitated in routine practice.


Asunto(s)
Medicina Familiar y Comunitaria , Conocimientos, Actitudes y Práctica en Salud , Circunferencia de la Cintura , Adulto , Anciano , Asia Sudoriental/etnología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Investigación Cualitativa , Medición de Riesgo , Reino Unido/epidemiología , Circunferencia de la Cintura/fisiología
11.
Nat Commun ; 10(1): 2115, 2019 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-31073170

RESUMEN

Approximately 30% of ERα breast cancer patients relapse with metastatic disease following adjuvant endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain undergoes epigenetic reprogramming in aromatase inhibitors (AI)-resistant cells, leading to Keratin-80 (KRT80) upregulation. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion and cellular stiffening, collectively promoting cancer cell invasion. Shearwave elasticity imaging performed on prospectively recruited patients confirms KRT80 levels correlate with stiffer tumors. Immunohistochemistry showed increased KRT80-positive cells at relapse and, using several clinical endpoints, KRT80 expression associates with poor survival. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/patología , Citoesqueleto/patología , Queratinas Tipo II/genética , Recurrencia Local de Neoplasia/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Citoesqueleto/genética , Resistencia a Antineoplásicos/genética , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Queratinas Tipo II/metabolismo , Células MCF-7 , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Dominios Proteicos/genética , Regulación hacia Arriba
14.
J Racial Ethn Health Disparities ; 4(6): 1107-1119, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-27928772

RESUMEN

Minority ethnic populations experience a disproportionate burden of health inequalities compared with the rest of the population, including an increased risk of type 2 diabetes (T2DM). The purpose of this narrative review was to explore knowledge and attitudes around diabetes, physical activity and diet and identify barriers and facilitators to healthy lifestyle changes in minority ethnic populations in the UK. The narrative review focused on three key research topics in relation to barriers and facilitators to healthy lifestyle changes in minority adult ethnic populations: (i) knowledge and attitudes about diabetes risk; (ii) current behaviours and knowledge about physical activity and diet; and (iii) barriers and facilitators to living a healthier lifestyle. Nearly all of the studies that we identified reported on South Asian minority ethnic populations; we found very few studies on other minority ethnic populations. Among South Asian communities, there was generally a good understanding of diabetes and its associated risk factors. However, knowledge about the levels of physical activity required to gain health benefits was relatively poor and eating patterns varied. Barriers to healthy lifestyle changes identified included language barriers, prioritising work over physical activity to provide for the family, cultural barriers with regard to serving and eating traditional food, different perceptions of a healthy body weight and fear of racial harassment or abuse when exercising. Additional barriers for South Asian women included expectations to remain in the home, fear for personal safety, lack of same gender venues and concerns over the acceptability of wearing 'western' exercise clothing. Facilitators included concern that weight gain might compromise family/carer responsibilities, desire to be healthy, T2DM diagnosis and exercise classes held in 'safe' environments such as places of worship. Our findings suggest that South Asian communities are less likely to engage in physical activity than White populations and highlight the need for health promotion strategies to engage people in these communities. There is a gap in knowledge with regard to diabetes, physical activity, diet and barriers to healthy lifestyle changes among other ethnic minority populations in the UK; we recommend further research in this area.


Asunto(s)
Pueblo Asiatico/psicología , Etnicidad/psicología , Conocimientos, Actitudes y Práctica en Salud/etnología , Estilo de Vida Saludable , Grupos Minoritarios/psicología , Diabetes Mellitus/etnología , Diabetes Mellitus/psicología , Dieta/etnología , Dieta/psicología , Ejercicio Físico/psicología , Humanos , Reino Unido
15.
Endocr Connect ; 6(5): 323-330, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28515051

RESUMEN

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a lifelong condition. Its symptoms have been linked with psychological consequences, but less attention has been given to the daily implications of living with PCOS. We aimed to explore women's experiences living with PCOS, and the potential acceptability of group education sessions for this target group. METHODS: Women with PCOS were recruited from an ethnically diverse UK community. Twelve semi-structured interviews were conducted. Analysis was underpinned by the constant comparative approach and involved the identification and exploration of key themes. RESULTS: Participants reported a range of symptoms linked with PCOS, including problems relating to menstruation and weight difficulties. Hirsutism was reported as the most distressing symptom. Emergent themes included perceptions about symptoms and delays in receiving a diagnosis; psychological distress; practical implications of living with the condition; coping with PCOS and perceived support needs. Some findings were specific to cultural backgrounds. Participants were supportive of the idea of group education for women with PCOS and suggested a need to provide education within the community and health care providers. DISCUSSION: Women with PCOS experience high psychological distress and difficulties with coping with their condition. Suggested strategies to reduce the negative psychological impact include education at various levels.

16.
J Diabetes Res ; 2016: 8107108, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27703985

RESUMEN

Aims. To apply and assess the suitability of a model consisting of commonly used cross-cultural translation methods to achieve a conceptually equivalent Gujarati language version of the Leicester self-assessment type 2 diabetes risk score. Methods. Implementation of the model involved multiple stages, including pretesting of the translated risk score by conducting semistructured interviews with a purposive sample of volunteers. Interviews were conducted on an iterative basis to enable findings to inform translation revisions and to elicit volunteers' ability to self-complete and understand the risk score. Results. The pretest stage was an essential component involving recruitment of a diverse sample of 18 Gujarati volunteers, many of whom gave detailed suggestions for improving the instructions for the calculation of the risk score and BMI table. Volunteers found the standard and level of Gujarati accessible and helpful in understanding the concept of risk, although many of the volunteers struggled to calculate their BMI. Conclusions. This is the first time that a multicomponent translation model has been applied to the translation of a type 2 diabetes risk score into another language. This project provides an invaluable opportunity to share learning about the transferability of this model for translation of self-completed risk scores in other health conditions.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Emigrantes e Inmigrantes , Medición de Riesgo/métodos , Adulto , Índice de Masa Corporal , Competencia Cultural , Femenino , Humanos , India/etnología , Masculino , Persona de Mediana Edad , Traducciones , Reino Unido
17.
Chronic Illn ; 12(1): 3-17, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25827572

RESUMEN

OBJECTIVES: To explore the impact of Diabetes Education and Self Management for Ongoing and Newly Diagnosed (DESMOND) Foundation education, particularly from interviewees' narratives regarding recall of good and bad news messages and behaviour changes. METHODS: In-depth, semi-structured interviews were conducted with a purposive sample (n=19) of people who had attended education sessions as part of a randomised controlled trial in two UK sites with ethnically diverse populations. Data collection and analysis were informed by the constant comparative approach and facilitated through charting. RESULTS: Findings were similar in people from different ethnic backgrounds. Exploration of levels of recall of the sessions suggested that this was variable and sometimes very limited, but that interviewees had all assimilated some relevant learning. Key themes emerged relating to the way in which interviewees recalled and had been influenced by positive (good news) and negative (bad news) messages within the education sessions, including biomedical explanations. Both types of message appeared to have an important role in terms of motivation to change behaviour, but a notable observation was that none of the interviewees recalled receiving bad news messages when diagnosed. DISCUSSION: Our findings have highlighted the importance of providing and combining both negative and positive messages within education designed to promote self-management behaviour change.


Asunto(s)
Diabetes Mellitus Tipo 2/psicología , Conductas Relacionadas con la Salud , Motivación , Educación del Paciente como Asunto , Autocuidado , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Entrevistas como Asunto , Masculino , Investigación Cualitativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios
18.
Clin Cancer Res ; 22(23): 5929-5938, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27301701

RESUMEN

PURPOSE: CDK-activating kinase (CAK) is required for the regulation of the cell cycle and is a trimeric complex consisting of cyclin-dependent kinase 7 (CDK7), Cyclin H, and the accessory protein, MAT1. CDK7 also plays a critical role in regulating transcription, primarily by phosphorylating RNA polymerase II, as well as transcription factors such as estrogen receptor-α (ER). Deregulation of cell cycle and transcriptional control are general features of tumor cells, highlighting the potential for the use of CDK7 inhibitors as novel cancer therapeutics. EXPERIMENTAL DESIGN: mRNA and protein expression of CDK7 and its essential cofactors cyclin H and MAT1 were evaluated in breast cancer samples to determine if their levels are altered in cancer. Immunohistochemical staining of >900 breast cancers was used to determine the association with clinicopathologic features and patient outcome. RESULTS: We show that expressions of CDK7, cyclin H, and MAT1 are all closely linked at the mRNA and protein level, and their expression is elevated in breast cancer compared with the normal breast tissue. Intriguingly, CDK7 expression was inversely proportional to tumor grade and size, and outcome analysis showed an association between CAK levels and better outcome. Moreover, CDK7 expression was positively associated with ER expression and in particular with phosphorylation of ER at serine 118, a site important for ER transcriptional activity. CONCLUSIONS: Expressions of components of the CAK complex, CDK7, MAT1, and Cyclin H are elevated in breast cancer and correlate with ER. Like ER, CDK7 expression is inversely proportional to poor prognostic factors and survival. Clin Cancer Res; 22(23); 5929-38. ©2016 AACR.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas Portadoras/genética , Ciclina H/genética , Quinasas Ciclina-Dependientes/genética , Expresión Génica/genética , Receptores de Estrógenos/genética , Adulto , Proteínas de Ciclo Celular , Femenino , Humanos , Persona de Mediana Edad , Fosforilación/genética , Pronóstico , Transducción de Señal/genética , Factores de Transcripción , Transcripción Genética/genética , Quinasa Activadora de Quinasas Ciclina-Dependientes
19.
Clin Cancer Res ; 10(16): 5355-60, 2004 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-15328172

RESUMEN

PURPOSE: TEL (ETV6)-AML1 (RUNX1) chimeric gene fusions are frequent genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). They often arise prenatally as early events or initiating events and are complemented by secondary postnatal genetic events of which deletion of the non-rearranged, second TEL allele is the most common. This consistent sequence of molecular pathogenesis facilitates an analysis of the clonal origins of relapse in this leukemia, which has some unusual clinical features. EXPERIMENTAL DESIGN: We compared the boundaries, by microsatellite mapping, of TEL deletions at relapse versus diagnosis in 15 informative patients. Moreover, we compared the relatedness of diagnostic and relapse clones using immunoglobulin and T-cell receptor genes rearrangements and clonotypic TEL-AML1 genomic fusion. RESULTS: Five patients retained the apparent same size TEL deletion, seven had larger deletions, and three had smaller deletions at relapse. In all of the cases evaluated, the clonal relatedness of diagnostic and relapse cells was confirmed by the retention of clonotypic TEL-AML1 genomic sequence and/or at least one identical immunoreceptor gene rearrangement. CONCLUSIONS: These data provide further evidence that TEL deletions are secondary to TEL-AML1 fusions in ALL. They are compatible with the novel idea that in at least some cases of childhood ALL, remission occurs with persistence of a preleukemic "fetal" clone, and subsequent relapse reflects the emergence of a new subclone from this reservoir after an independent "second hit," i.e., independent TEL deletion. To our knowledge, the study is the most extensive and comprehensive analysis of the relationship between diagnostic and relapse clones in childhood ALL presented thus far.


Asunto(s)
Proteínas de Unión al ADN/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Eliminación de Secuencia , Factores de Transcripción/genética , Fusión Artificial Génica , Niño , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Bases de Datos Genéticas , Reordenamiento Génico de Linfocito T , Humanos , Repeticiones de Microsatélite , Proteínas Proto-Oncogénicas c-ets , Recurrencia , Proteína ETS de Variante de Translocación 6
20.
Patient Educ Couns ; 98(9): 1123-30, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26054453

RESUMEN

OBJECTIVES: To develop and pilot-test the feasibility and effectiveness of an interactive DVD about misconceptions within South Asian communities regarding insulin treatment in type 2 diabetes, for educating patients and community members and training healthcare providers. METHODS: The project setting was a South Asian (mainly Indian) community in Leicester, UK. Qualitative evidence from our previous studies was used to inform the content of the DVD script and accompanying resources. The intervention involved three components: facilitating DVD viewings for people with/without diabetes in community settings; training healthcare providers involved in managing South Asian patients with diabetes in primary care; and using the DVD and resources in primary care patient consultations. Evaluation involved a range of approaches including face-to-face interviews, telephone feedback and questionnaires. RESULTS: Analysis of questionnaires and qualitative feedback from community participants showed some significant changes in attitudes and understanding about insulin and high acceptability of the DVD. Healthcare providers who attended the training found it informative and perceived the DVD and visual resources as potentially useful for facilitating acceptance of insulin. Primary care patient recruitment was challenging, but participants described the DVD as an acceptable and informative way of learning about insulin therapy. CONCLUSION: The DVD intervention was effective and feasible at community and healthcare provider levels. PRACTICE IMPLICATIONS: Although based on a small sample, at patient level our findings suggested that the DVD worked at different levels helping some to accept the need for insulin and others to consolidate a decision to commence this treatment. Consideration needs to be given to patient engagement strategies for implementation in primary care consultations.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Personal de Salud/educación , Educación del Paciente como Asunto , Pueblo Asiatico , Actitud del Personal de Salud , Discos Compactos , Diabetes Mellitus Tipo 2/etnología , Femenino , Humanos , Insulina , Masculino , Selección de Paciente , Atención Primaria de Salud , Derivación y Consulta , Encuestas y Cuestionarios , Reino Unido
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