The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development.

Schistosomiasis affects millions of people in developing countries and is responsible for more than 200,000 deaths annually. Because of toxicity and limited spectrum of activity of alternatives, there is effectively only one drug, praziquantel, available for its treatment. Recent data suggest that drug resistance could soon be a problem. There is therefore the need to identify new drug targets and develop drugs for the treatment of schistosomiasis. Analysis of the Schistosoma mansoni genome sequence for proteins involved in detoxification processes found that it encodes a single cytochrome P450 (CYP450) gene. Here we report that the 1452 bp open reading frame has a characteristic heme-binding region in its catalytic domain with a conserved heme ligating cysteine, a hydrophobic leader sequence present as the membrane interacting region, and overall structural conservation. The highest sequence identity to human CYP450s is 22%. Double stranded RNA (dsRNA) silencing of S. mansoni (Sm)CYP450 in schistosomula results in worm death. Treating larval or adult worms with antifungal azole CYP450 inhibitors results in worm death at low micromolar concentrations. In addition, combinations of SmCYP450-specific dsRNA and miconazole show additive schistosomicidal effects supporting the hypothesis that SmCYP450 is the target of miconazole. Treatment of developing S. mansoni eggs with miconazole results in a dose dependent arrest in embryonic development. Our results indicate that SmCYP450 is essential for worm survival and egg development and validates it as a novel drug target. Preliminary structure-activity relationship suggests that the 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol moiety of miconazole is necessary for activity and that miconazole activity and selectivity could be improved by rational drug design

Perceived barriers and benefits to physical activity in colorectal cancer patients

There is emerging evidence for the benefits of physical activity (PA) post-diagnosis for colorectal cancer (CRC) survivors. However, population studies suggest activity levels in these patients are very low. Understanding perceived barriers and benefits to activity is a crucial step in designing effective interventions

The Lifestyle Information and Intervention Preferences of Teenage and Young Adult Cancer Survivors: A Qualitative Study

Background: Little is currently known about how best to promote healthy lifestyle choices among teenage and young adult (TYA) cancer survivors. Such data gathered from a patient-centered perspective are instrumental for the development of health behavior change interventions for young people with cancer. Objective: This study aimed to explore the lifestyle information needs of TYA cancer survivors and their preferences regarding lifestyle information and intervention delivery. Lifestyle behaviors of interest were physical activity, diet, smoking, alcohol consumption, and sun safety. Methods: A total of 13 TYA cancer survivors (mean age, 22.9 years) participated in 10 individual interviews and 1 focus group (n = 3). Each interview and focus group followed the same semistructured interview guide, which was designed to explore young peoples’ motivation behind leading a healthy lifestyle, their past experience of searching for lifestyle information, and their preferences relating to lifestyle information delivery. Results: Three core themes emerged: cancer as a catalyst to lifestyle behavior change, factors influencing health behavior change, and health behavior information preferences. Social support emerged as facilitator of both health behavior change and self-efficacy. Conclusion: Young people with cancer want age-appropriate lifestyle information on a range of topics delivered in multiple formats at various time points. Implications for Practice: Health professionals working with TYA cancer survivors should address young peoples’ lifestyle information needs throughout the cancer care pathway and support young people to foster the confidence to make, and sustain, positive lifestyle behavior changes

A qualitative exploration of physical, mental and ocular fatigue in patients with primary Sjögren's Syndrome

Introduction Primary Sjögren's Syndrome (pSS) affects exocrine glands such as those producing the tear film, leading to dry and painful eyes, but is also associated with fatigue. The experience of fatigue in pSS, and its relationship with sicca symptoms, is poorly understood. Methods Twenty people diagnosed with pSS were recruited to participate in a semi-structured qualitative interview about their symptoms experience. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results People with pSS described physical tiredness, mental fatigue and ocular fatigue. Mental fatigue was characterised by difficulties in attention, particularly, the ability to follow conversations and short-term memory problems. Participants linked their experience of fatigue to feeling of depression, frustration, irritation and anxiety, and therefore, fatigue was suggested to have had a large impact on their psychological well-being. People with pSS also described a range of ocular symptoms including pain, dryness, and itching, which were compounded by fatigue. For some, eye fatigue was pervasive, and daily activities involving the eyes such as reading, using the computer and driving were impaired. In some cases, the level of ocular discomfort was so severe it prevented sleep, which in turn impacted on general fatigue levels. Conclusions People with pSS experience fatigue in a range of ways; physical, mental and ocular fatigue were described. Fatigue was suggested to exacerbate other ocular symptoms, posed serious physical limitations and caused psychological distress. Further research into the nature of fatigue and ocular symptoms in pSS is required

Determinants of sleep quality in 5835 individuals living with and beyond breast, prostate, and colorectal cancer: a cross-sectional survey

Purpose: The present study aimed to quantify the level of sleep problems in 5835 breast, prostate, and colorectal cancer survivors, and explore a number of potential determinants of poor sleep quality in the present sample. BMI, diet, and physical activity were of particular interest as potential determinants. / Methods: Participants who completed the ‘Health and Lifestyle after Cancer’ survey were adults who had been diagnosed with breast, prostate, or colorectal cancer (mean time since cancer diagnosis was 35.5 months, SD=13.56). Sleep quality was assessed using the Pittsburgh Sleep Quality Index. BMI was calculated from self-reported height and weight. Participants were categorised as meeting/not meeting the World Cancer Research Fund (WCRF) recommendations for fibre, fruit and vegetables, added sugar, red meat, processed meat, fat, alcohol, and physical activity. Analyses accounted for demographic and clinical factors. / Results: Fifty-seven percent of those with sleep data were classified as poor sleepers (response rate 79%). Being female, having a higher number of cancer treatments, more comorbid conditions, and being more anxious/depressed increased the odds of being a poor sleeper. After adjustment for these factors, there were no associations between diet/alcohol/physical activity and sleep. However, BMI was associated with sleep. Individuals in the overweight and obese categories had 22% and 79% higher odds of being poor sleepers than individuals in the underweight/healthy weight category, respectively. / Conclusions: The findings suggest that there may be a need to develop sleep quality interventions for cancer survivors with obesity. Even after adjustment for multiple clinical and demographic factors, BMI (particularly obesity) was associated with poor sleep. Thus, researchers and health professionals should find ways to support individuals with overweight and obesity to improve their sleep quality

Country differences in the diagnosis and management of coronary heart disease : a comparison between the US, the UK and Germany

Background The way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany. Methods Videotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions. Results Results show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice. Conclusion Although all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process

Community based rehabilitation: a strategy for peace-building

BACKGROUND: Certain features of peace-building distinguish it from peacekeeping, and make it an appropriate strategy in dealing with vertical conflict and low intensity conflict. However, some theorists suggest that attempts, through peace-building, to impose liberal values upon non-democratic cultures are misguided and lack an ethical basis. DISCUSSION: We have been investigating the peace-building properties of community based approaches to disability in a number of countries. This paper describes the practice and impact of peace-building through Community Based Rehabilitation (CBR) strategies in the context of armed conflict. The ethical basis for peace-building through practical community initiatives is explored. A number of benefits and challenges to using CBR strategies for peace-building purposes are identified. SUMMARY: During post-conflict reconstruction, disability is a powerful emotive lever that can be used to mobilize cooperation between factions. We suggest that civil society, in contrast to state-level intervention, has a valuable role in reducing the risks of conflict through community initiatives

The adapted Zelen was a feasible design to trial exercise in myeloma survivors

OBJECTIVE: We utilised a method rarely seen in cancer behavioural trials to explore methods of overcoming difficulties often seen in randomised controlled trials. We report our experiences of the adapted-Zelen design, so that other researchers can consider this approach for behavioural trials. STUDY DESIGN: & Setting:The adapted-Zelen design was used to explore the effects of exercise on multiple myeloma patients fatigue, quality of life and physical outcomes. All participants consented to an observational cohort study of lifestyle factors, but were unaware of subsequent randomisation to remain in cohort only group or be offered an exercise intervention requiring second consent. RESULTS: Due to lower than expected uptake rate to the exercise offered group (57%), the length of recruitment increased from 24 to 29 months to ensure power was reached. At enrolment patients were unaware of the potential increased commitment and as a result 62% of participants allocated to the intervention declined due to the extra time/travel commitment required. This emulates clinical settings and suggests improvements in intervention delivery are required. Dropout rates from the cohort only group were similar to designs that provide the control with the intervention. Our results from the main study do not suggest contamination occurred despite some anecdotal evidence. CONCLUSION: Future use of this design warrants careful consideration of the study resources and recruitment time frames required but holds potential value in reducing contamination, control group dissatisfaction and resulting drop out. Adapted-Zelen design reduces selection bias and therefore gives clinicians a better understanding of acceptability in clinical settings. Future studies should evaluate control group experiences of the design and formally record contamination throughout the study to confirm its acceptability