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BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Age is the strongest non-modifiable risk factor but it is estimated that over half of CRC cases are linked with lifestyle factors such as diet. The Biomarkers Of RIsk of Colorectal Cancer (BORICC) Study recruited 363 participants in 2005 to investigate the effects of lifestyle factors on biomarkers of CRC risk. AIM: In the present BORICC Follow-Up (BFU) Study, we are using a longitudinal study design to investigate the effects of ageing (12+ years) and lifestyle factors on biomarkers of CRC risk and on healthy ageing. METHODS: BFU Study participants attended a study visit at North Tyneside General Hospital (UK) for collection of biological samples, including blood and rectal biopsies, and information collected included anthropometric measurements, a Health & Medications Questionnaire, physical activity and sedentary behaviour, and habitual diet. Furthermore, musculoskeletal function was assessed by heel bone densitometry, timed up and go and hand grip strength as markers of healthy ageing. The BFU Study outcomes will be similar to those measured at baseline in the BORICC Study, such as DNA methylation and mitochondrial function, with additional measurements including the gut microbiome, faecal short-chain fatty acid concentrations and expression of genes associated with CRC. RESULTS: Participants' recruitment to BFU Study and all sample and data collection have been completed. Forty-seven of the original BORICC participants were re-recruited to the BFU Study (mean age 67 years, 51% female). The recruits included 37 initially healthy participants and 10 participants who had adenomatous polyps at baseline. Approximately 70% of participants were over-weight or obese. CONCLUSION: Ultimately, identifying lifestyle factors that can reduce CRC risk, and understanding the underlying mechanisms for the effects of lifestyle and ageing on CRC risk, could lead to early prevention strategies.

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Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.

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Pre-term delivery is the leading cause of neonatal mortality and morbidity. The aim of this study is to determine the diagnostic accuracy of the fetal fibronectin (FF) test in predicting pre-term birth, the test interpretation and subsequent action taken in normal clinical practice in a busy tertiary centre setting. A total of 133 symptomatic women were included in the study and underwent the FF test. The use of tocolysis and corticosteroids were significantly greater in test-positive patients (p < 0.001). A negative test for detecting pre-term delivery within 10 days of the test was 100% sensitive with 100% negative predictive value (NPV). Our study has confirmed that a negative FF is an excellent short-term test to exclude pre-term delivery. The use of FF testing in routine clinical practice results in test characteristics similar to those found in research studies. This implies that the conclusions reached by researchers can be reliably translated into clinical practice.

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OBJECTIVE: To understand differences in the context of, and reasons for, smoking initiation among boys and girls. STUDY DESIGN: Sex- and gender-based analysis of published literature. METHODS: A comprehensive search of the PUBMED database was conducted for studies (published in the English language) between January 1980 and October 2010 that assessed smoking initiation among children and adolescents (aged 8-19 years). Information on demographics and study design were extracted by two authors from each eligible article. A sex- and gender-based analysis was employed. RESULTS: Of 40 publications initially obtained, studies in adult or college-age populations (n = 9) and studies that did not examine the specific context of smoking initiation (n = 19) were excluded. Thus, this review is based on 12 eligible studies. Eligible studies represented data from 10,831 children and adolescents in nine countries. In most studies, boys had a lower age of smoking initiation than girls, with the exception of two studies from Yemen and China. In some countries, girls reported obtaining and smoking their first cigarette from family members at home. In most studies, the school was the main setting for initiation for boys, whereas the home setting was the main setting for girls. CONCLUSIONS: This study highlights gender and cultural differences in smoking initiation among children and adolescents. Smoking prevention programmes should thus include gender- and culture-specific content related to smoking initiation. Future studies may further examine gender- and culture-specific messaging to inform policies and enhance tailored programmes aimed at preventing smoking initiation.

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Cytochrome c oxidase or mitochondrial respiratory chain complex IV is where over 90% of oxygen is consumed. The relationship between complex IV activity and mitochondrial proteins, which provides a guide to understanding the mechanisms in primary mitochondrial disorders, has been determined by histochemistry (activity) and immunohistochemistry in serial sections. In the central nervous system (CNS), mitochondrial activity and immunoreactivity have been determined in populations of cells in serial sections as capturing cells in more than one section is difficult. In this report we describe a method to determine complex IV activity in relation to mitochondrial proteins at a single cell level in the CNS. We performed complex IV histochemistry and immunohistochemistry consecutively in snap frozen sections. Although the product of complex IV histochemistry reduces the sensitivity of standard immunohistochemistry (secondary antibody and ABC method) the biotin-free Menapath polymer detection system (A. Menarini Diagnostics, Wokingham, UK) enables mitochondrial proteins to be detected following complex IV histochemistry. The co-occurring chromogens may then be separately visualised and analysed using multi-spectral imaging (Nuance system CRi, Woburn, MA). Our technique is applicable for exploring mitochondrial defects within single cells in a variety of CNS disorders and animal models of those diseases.

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OBJECTIVES: To analyse the experiences of youths accessing sexually transmitted infection (STI) services and to examine the perspectives of service providers in four British Columbia communities. METHODS: In-depth qualitative interviews were completed with 70 young men and women (15-24 years). In total, 22 service providers (for example, clinicians, staff) were interviewed about their experiences providing STI testing services as well as the policies and practice guidelines that inform their work with youths. In addition, naturalistic observation was conducted at 11 clinic sites, including: youth clinics, doctors' offices, public health units and a large clinic specialising in STI testing. RESULTS: "Youth-friendly" STI testing services were rare despite being strongly desired by youth and service providers. Participants identified five barriers to accessing and/or providing youth-friendly STI testing: geography isolates many youths from testing service times or services, and presents privacy concerns, especially for rural youths. Clinic décor was perceived to be tailored for women and most service providers were female. Disclosing risky sexual behaviour to clinicians may be difficult for youths, especially for lesbian, gay, bisexual and transgender youths-particularly in contexts that are perceived to be homophobic. Many young women mistakenly believe that Pap smears include STI testing procedures, while many young men avoid testing because they fear the urethral swab and are unaware of alternative methods of specimen collection. CONCLUSION: This research reveals how structural and socio-cultural forces (for example, gender, place, physical space, culture) interact to shape the experiences of youths accessing STI testing services.

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UNLABELLED: Accurate measurement of cartilage deformation in loaded cadaver hip joints could be a valuable tool to answer clinically relevant research questions. MRI is a promising tool, but its use requires an understanding of cartilage deformation and recovery properties in the intact hip. Our objective was to answer the following questions: (1) How long does it take for hip cartilage to reach a deformed steady-state thickness distribution under simulated physiological load, and how much does the cartilage deform? (2) How long does it take for hip cartilage to return to the original cartilage thickness distribution once the load is removed? METHODS: Five human hip specimens were axially loaded to 1980N in a 7T MR scanner and scanned every 15min throughout loading. One specimen was scanned every hour throughout recovery from load. One repeatability specimen was loaded and scanned every day for 4 days. Hip cartilage was segmented as a single unit and thickness was measured radially. RESULTS: The hip cartilage reached a steady-state thickness distribution after 225min of load, and 16.5h of recovery. Mean strain after 225min of load was 30.9%. The repeatability specimen showed an average day-to-day change in mean cartilage thickness of 0.10mm over 4 days of data collection. The amount of deformation (0.96mm) was far greater than the image resolution (0.11mm) and error due to repeatability (0.10mm). CONCLUSION: Using an ex vivo model, this method has potential for assessing changes in hip cartilage strain due to injury or surgical intervention.

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Medical students frequently have questions about the specialty of family practice. Responses to 30 questions commonly asked about family practice are presented with a review of recent literature. These responses may assist medical students and their advisors in considering the choice of family practice as a career.

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In this study predictors of successful smoking cessation among 166 clients of a smoking cessation program were examined via multiple regression analyses. Results showed that seven significant predictors accounted for 25% of the variance in successful smoking cessation. Abstainers tended to have higher incomes, to rate pregnancy as a motivation more highly, to have made fewer previous attempts to quit, to be low on habit smoking, to crave cigarettes more in low-arousal situations, to be stimulus reducers, and to be older.

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