Transcription specificity of Xenopus laevis RNA polymerase A

Based on a combination of an Ugi four component reaction and a ring closing metathesis, a library of novel artificial macrocyclic inhibitors of the p53-MDM2 interaction was designed and synthesized. These macrocycles, alternatively to stapled peptides, target for the first time the large hydrophobic surface area formed by Tyr67, Gln72, His73, Val93, and Lys94 yielding derivatives with affinity to MDM2 in the nanomolar range. Their binding affinity with MDM2 was evaluated using fluorescence polarization (FP) assay and 1H-15N two-dimensional HSQC nuclear magnetic resonance experiments

‘A false sense of security’? Understanding the role of the HPV vaccine on future cervical screening behaviour: a qualitative study of UK parents and girls of vaccination age

OBJECTIVES: The UK Human Papillomavirus (HPV) vaccination programme was introduced in 2008 for girls aged 12-13. The vaccine offers protection against HPV types 16 and 18, which together cause about 70% of cervical cancers. Vaccinated girls will receive future invitations to the NHS Cervical Screening Programme, to prevent cancers associated with HPV types not included in the vaccine, and in case of prior infection with HPV 16 or 18. Little is known about parents' and girls' understandings of the protection offered by the vaccine, or the need for future screening. DESIGN: Qualitative interviews with twenty-six parents, and nine girls aged 12-13 who were offered HPV vaccination through a Primary Care Trust (PCT) in the South-east of England, UK. SETTING: Thirty-nine schools, and four general practices. RESULTS: Uncertainty about the level of protection offered by the HPV vaccine was evident among parents, and to a lesser extent among vaccination-aged girls. There was a lack of understanding among parents and girls that cervical screening would be required irrespective of vaccination status; some parental decisions to accept the vaccine were made on the misunderstanding that vaccination provided complete protection against cervical cancer. CONCLUSIONS: Sufficient awareness of the issues related to screening is necessary for informed decision-making about whether or not to accept the HPV vaccine. Clearer information is needed concerning the incomplete protection offered by the vaccine, and that cervical screening will still be required. Future invitations for cervical screening should stress the necessity to attend regardless of HPV vaccination status, to ensure that high levels of prevention of cervical cancer through screening are maintained

Diagnosed with breast cancer whilst on a family history screening programme: an exploratory qualitative study

Mammographic screening is offered to many women under 50 in the UK who are at moderate or high risk of developing breast cancer because of their family history of the disease. Little is understood about the impact of screening on the emotional well-being of women with a family history of breast cancer. This qualitative study explores the value that women at increased risk placed on screening, both pre- and post-cancer diagnosis and the impact of the diagnosis. In-depth interviews were undertaken with 12 women, aged 35-50, diagnosed with breast cancer while on an annual mammographic screening programme. Women described the strong sense of reassurance gained from screening prior to diagnosis. This faith in screening was reinforced by early detection of their cancer. Reactions to diagnosis ranged from devastation to relief at having finally developed a long-expected condition. Despite their positive attitudes about screening, not all women wanted to continue with surveillance. For some, prophylactic mastectomy was preferable, to reduce future cancer risk and to alleviate anxieties about the detection of another cancer at each subsequent screen. This study illustrates the positive yet diverse attitudes towards mammographic screening in this group of women with a family history of breast cancer

What is the psychological impact of mammographic screening on younger women with a family history of breast cancer? Findings from a prospective cohort study (PIMMS)

PURPOSE: Studies are underway to establish the clinical effectiveness of annual mammographic screening in women younger than 50 years with a family history of breast cancer. This study investigated both the positive and negative psychological effects of screening on these women. PATIENTS AND METHODS: Women who received an immediate all-clear result after mammography (n = 1,174) and women who were recalled for additional tests before receiving an all-clear result (false positive; n = 112) completed questionnaires: 1 month before mammography, and 1 and 6 months after receiving final results. The questionnaires included measures of cancer worry, psychological consequences, and perceived benefits of breast screening. RESULTS: Women who received an immediate all-clear result experienced a decrease in cancer worry and negative psychological consequences immediately after the result, whereas women who were recalled for additional tests did not. By 6 months this cancer-specific distress had reduced significantly in both groups. Changes in levels of distress were significantly different between the two groups, but in absolute terms the differences were not large. Recalled women reported significantly greater positive psychological consequences of screening immediately after the result, and were also more positive about the benefits of screening compared with women who received an immediate all-clear result. CONCLUSION: For women receiving an immediate all-clear result, participating in annual mammographic screening is psychologically beneficial. Furthermore, women who are recalled for additional tests do not appear to be harmed by screening: these women's positive views about mammography suggest that they view any distress caused by recall as an acceptable part of screening

Barriers to early diagnosis of symptomatic breast cancer: a qualitative study of Black African, Black Caribbean and White British women living in the UK

Objectives: Understanding barriers to early diagnosis of symptomatic breast cancer among Black African, Black Caribbean and White British women in the UK. Design: In-depth qualitative interviews using grounded theory methods to identify themes. Findings validated through focus groups. Participants: 94 women aged 33–91 years; 20 Black African, 20 Black Caribbean and 20 White British women diagnosed with symptomatic breast cancer were interviewed. Fourteen Black African and 20 Black Caribbean women with (n=19) and without (n=15) breast cancer participated in six focus groups. Setting: Eight cancer centres/hospital trusts in London (n=5), Somerset (n=1), West Midlands (n=1) and Greater Manchester (n=1) during 2012–2013. Results: There are important differences and similarities in barriers to early diagnosis of breast cancer between Black African, Black Caribbean and White British women in the UK. Differences were influenced by country of birth, time spent in UK and age. First generation Black African women experienced most barriers and longest delays. Second generation Black Caribbean and White British women were similar and experienced fewest barriers. Absence of pain was a barrier for Black African and Black Caribbean women. Older White British women (≥70 years) and first generation Black African and Black Caribbean women shared conservative attitudes and taboos about breast awareness. All women viewed themselves at low risk of the disease, and voiced uncertainty over breast awareness and appraising non-lump symptoms. Focus group findings validated and expanded themes identified in interviews. Conclusions: Findings challenged reporting of Black women homogenously in breast cancer research. This can mask distinctions within and between ethnic groups. Current media and health promotion messages need reframing to promote early presentation with breast symptoms. Working with communities and developing culturally appropriate materials may lessen taboos and stigma, raise awareness, increase discussion of breast cancer and promote prompt help-seeking for breast symptoms among women with low cancer awareness

Development and Evaluation of Educational Materials for Primary Care on Familial Breast and/or Ovarian Cancer

This article has no abstract

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

Screening Uptake in a Well-Established Diabetic Retinopathy Screening Program: The role of geographical access and deprivation

OBJECTIVE—To identify criteria that affect uptake of diabetes retinal screening in a community screening program using mobile retinal digital photography units

Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma