Breast cancer survivors' perspectives on a weight loss and physical activity lifestyle intervention.

PURPOSE: The purpose of this study is to qualitatively describe the experiences of breast cancer survivors who took part in a successful 24-week lifestyle intervention aimed at weight loss. The aim was to inform future study designs and lifestyle interventions. METHODS: Nine women who completed the lifestyle intervention took part in either a focus group or telephone interviews with trained facilitators who were not involved in the delivery of the intervention. Interviews were transcribed verbatim and thematic analysis was conducted. RESULTS: Women appreciated the group-based nature of the program, the presence of other breast cancer survivors, and the safe and supportive environment provided by program leaders. The intervention supported women in reframing their dietary habits, and the exercise component had unexpected benefits on their psychological wellbeing. The logistics of fitting the intervention into busy work and family schedules was a challenge experienced by most women. Recommendations for future programming included offering the intervention to all survivors immediately following adjuvant treatment, integrating participants' social networks into the program and including a maintenance phase for sustainability of healthy behaviors. CONCLUSION: This qualitative study provides insight into breast cancer survivors' experiences in a group-based lifestyle intervention and offers suggestions for the development of future lifestyle programming in cancer care.

Attention to principles of exercise training: a review of exercise studies for survivors of cancers other than breast.

OBJECTIVES: Randomised controlled trials (RCTs) can evaluate how well a particular exercise programme reduces cancer treatment-related side effects. Adequate design and reporting of the exercise prescription employed in RCTs is central to interpreting study findings and translating effective interventions into practice. Our previous review on the quality and reporting of exercise prescriptions in RCTs in breast cancer survivors revealed several inadequacies. This review similarly evaluates exercise prescriptions used in RCTs in patients with cancers other than the breast. METHODS: The literature was searched for RCTs in persons diagnosed with a cancer other than breast. Data were extracted to evaluate the attention to the principles of exercise training in the study design and the reporting of and adherence to the exercise prescription used for the intervention. RESULTS: Of the 33 studies reviewed, none attended to all of the exercise training principles. Specificity was applied by 89%, progression by 26%, overload by 37%, initial values by 26%, diminishing returns by 9% and reversibility by 3%. Only 2 of 33 studies (6%) reported both the exercise prescription in full and adherence to each individual component of the prescription. CONCLUSIONS: Application of the principles of training in exercise RCTs of non-breast cancer survivors was incomplete and inconsistent. Given these observations, interpretation of findings from the reviewed studies should consider potential shortcomings in intervention design. Though the prescribed exercise programme was often described, adherence to the entire prescription was rarely reported providing a less accurate picture of dose-response and challenges in translating programmes to community settings.

Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors.

PURPOSE: Fatigue is one of the most commonly reported side effects during treatment for breast cancer and can persist following treatment completion. Cancer-related fatigue after treatment is multifactorial in nature, and one hypothesized mechanism is cardiorespiratory and neuromuscular deconditioning. The purpose of this study was to compare cardiorespiratory and neuromuscular function in breast cancer survivors who had completed treatment and met the specified criteria for cancer-related fatigue and a control group of breast cancer survivors without fatigue. METHODS: Participants in the fatigue (n = 16) and control group (n = 11) performed a maximal exercise test on a cycle ergometer for determination of peak power, power at lactate threshold, and VO(2) peak. Neuromuscular fatigue was induced with a sustained submaximal contraction of the right quadriceps. Central fatigue (failure of voluntary activation) was evaluated using twitch interpolation, and peripheral fatigue was measured with an electrically evoked twitch. RESULTS: Power at lactate threshold was lower in the fatigue group (p = 0.05). There were no differences between groups for power at lactate threshold as percentage of peak power (p = 0.10) or absolute or relative VO(2) peak (p = 0.08 and 0.33, respectively). When adjusted for age, the fatigue group had a lower power at lactate threshold (p = 0.02) and absolute VO(2) peak (p = 0.03). There were no differences between groups in change in any neuromuscular parameters after the muscle-fatiguing protocol. CONCLUSIONS: Findings support the hypothesis that cardiorespiratory deconditioning may play a role in the development and persistence of cancer-related fatigue following treatment. Future research into the use of exercise training to reduce cardiorespiratory deconditioning as a treatment for cancer-related fatigue is warranted to confirm these preliminary findings.

Review of exercise studies in breast cancer survivors: attention to principles of exercise training.

OBJECTIVES: Research supports the use of exercise to improve quality of life and reduce the side effects of breast cancer treatment, such as fatigue and decreased aerobic capacity. Previously published reviews have focused on reporting the outcomes of exercise interventions, but have not critically examined the exercise prescriptions. The purpose of this review is to evaluate the application of the principles of exercise training in the exercise prescriptions reported in intervention studies for breast cancer survivors. METHODS: Databases were searched for randomised controlled trials of exercise in women diagnosed with breast cancer. Data were extracted to evaluate the application of the principles of exercise training, the reporting of the components of the exercise prescription and the reporting of adherence to the exercise prescription. RESULTS: Of the 29 papers included, none applied all principles of exercise training. Specificity was applied by 64%, progression by 41%, overload by 31%, initial values by 62% and diminishing returns and reversibility by 7% of trials. No study reported all components of the exercise prescription. CONCLUSION: The application of the principles of exercise training varied greatly, and reporting of the exercise prescribed and completed was incomplete. When principles of exercise training are applied to the development of exercise protocols, there is greater confidence that non-significant findings reflect lack of efficacy of exercise rather than deficiencies in the prescription. Incomplete reporting of the exercise prescription and adherence to the prescription limits the reproducibility of the intervention, and the ability to determine the dose of exercise received by participants.

High yield primary microglial cultures using granulocyte macrophage-colony stimulating factor from embryonic murine cerebral cortical tissue.

BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF. Microglial expression of CD45, CD11b, CD11c, MHC class I and II, CD40, CD80, and CD86 was analyzed by flow cytometry and compared to those isolated using different culture methods and to the BV-2 cell line. GM-CSF microglia immunoreactivity and cytokine production was examined in response to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). RESULTS: Our results demonstrate GM-CSF addition during microglial culture yields higher cell numbers with greater purity than conventionally cultured primary microglia. We found that the expression of immune markers by GM-CSF microglia more closely resemble adult microglia than other methods or an immortalized BV-2 cell line. Primary differences amongst the different groups were reflected in their levels of CD39, CD86 and MHC class I expression. GM-CSF microglia produce CCL2, tumor necrosis factor-α, IL-6 and IL-10 following exposure to LPS and alter costimulatory marker expression in response to LPS or IFN-γ. Notably, GM-CSF microglia were often more responsive than the commonly used BV-2 cell line which produced negligible IL-10. CONCLUSION: GM-CSF cultured microglia closely model the phenotype of adult microglia examined ex vivo. GM-CSF microglia are robust in their responses to inflammatory stimuli, altering immune markers including Iba-1 and expressing an array of cytokines characteristic of both pro-inflammatory and reparative processes. Consequently, the addition of GM-CSF for the culturing of primary microglia serves as a valuable method to increase the potential for studying microglial function ex vivo.

Reliability and validity of the Performance Recorder 1 for measuring isometric knee flexor and extensor strength.

BACKGROUND: Muscular strength is a key parameter of rehabilitation programs and a strong predictor of functional capacity. Traditional methods to measure strength, such as manual muscle testing (MMT) and hand-held dynamometry (HHD), are limited by the strength and experience of the tester. The Performance Recorder 1 (PR1) is a strength assessment tool attached to resistance training equipment and may be a time- and cost-effective tool to measure strength in clinical practice that overcomes some limitations of MMT and HHD. However, reliability and validity of the PR1 have not been reported. METHODS: Test-retest and inter-rater reliability was assessed using the PR1 in healthy adults (n = 15) during isometric knee flexion and extension. Criterion-related validity was assessed through comparison of values obtained from the PR1 and Biodex® isokinetic dynamometer. RESULTS: Test-retest reliability was excellent for peak knee flexion (intra-class correlation coefficient [ICC] of 0.96, 95% CI: 0.85, 0.99) and knee extension (ICC = 0.96, 95% CI: 0.87, 0.99). Inter-rater reliability was also excellent for peak knee flexion (ICC = 0.95, 95% CI: 0.85, 0.99) and peak knee extension (ICC = 0.97, 95% CI: 0.91, 0.99). Validity was moderate for peak knee flexion (ICC = 0.75, 95% CI: 0.38, 0.92) but poor for peak knee extension (ICC = 0.37, 95% CI: 0, 0.73). CONCLUSIONS: The PR1 provides a reliable measure of isometric knee flexor and extensor strength in healthy adults that could be used in the clinical setting, but absolute values may not be comparable to strength assessment by gold-standard measures.

Feasibility of a lifestyle intervention on body weight and serum biomarkers in breast cancer survivors with overweight and obesity.

Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre-post test design, conducted from November 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle intervention modeled on the Diabetes Prevention Program in early stage breast cancer survivors (N=14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were completed at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were postmenopausal women aged 54.6±8.3 years with obesity (body mass index 30.1±3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8±5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8±1.2 kg at 36 weeks. In exploratory analysis, participants who lost >7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Prevention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs.

Whole-genome profiling of mutagenesis in Caenorhabditis elegans.

Deep sequencing offers an unprecedented view of an organism's genome. We describe the spectrum of mutations induced by three commonly used mutagens: ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), and ultraviolet trimethylpsoralen (UV/TMP) in the nematode Caenorhabditis elegans. Our analysis confirms the strong GC to AT transition bias of EMS. We found that ENU mainly produces A to T and T to A transversions, but also all possible transitions. We found no bias for any specific transition or transversion in the spectrum of UV/TMP-induced mutations. In 10 mutagenized strains we identified 2723 variants, of which 508 are expected to alter or disrupt gene function, including 21 nonsense mutations and 10 mutations predicted to affect mRNA splicing. This translates to an average of 50 informative mutations per strain. We also present evidence of genetic drift among laboratory wild-type strains derived from the Bristol N2 strain. We make several suggestions for best practice using massively parallel short read sequencing to ensure mutation detection.

Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis.

OBJECTIVES: Our aim was to determine the frequency of genomic imbalances in neonates with birth defects by using targeted array-based comparative genomic hybridization, also known as chromosomal microarray analysis. METHODS: Between March 2006 and September 2007, 638 neonates with various birth defects were referred for chromosomal microarray analysis. Three consecutive chromosomal microarray analysis versions were used: bacterial artificial chromosome-based versions V5 and V6 and bacterial artificial chromosome emulated oligonucleotide-based version V6 Oligo. Each version had targeted but increasingly extensive genomic coverage and interrogated>150 disease loci with enhanced coverage in genomic rearrangement-prone pericentromeric and subtelomeric regions. RESULTS: Overall, 109 (17.1%) patients were identified with clinically significant abnormalities with detection rates of 13.7%, 16.6%, and 19.9% on V5, V6, and V6 Oligo, respectively. The majority of these abnormalities would not be defined by using karyotype analysis. The clinically significant detection rates by use of chromosomal microarray analysis for various clinical indications were 66.7% for "possible chromosomal abnormality"+/-"others" (other clinical indications), 33.3% for ambiguous genitalia+/-others, 27.1% for dysmorphic features+multiple congenital anomalies+/-others, 24.6% for dysmorphic features+/-others, 21.8% for congenital heart disease+/-others, 17.9% for multiple congenital anomalies+/-others, and 9.5% for the patients referred for others that were different from the groups defined. In all, 16 (2.5%) patients had chromosomal aneuploidies, and 81 (12.7%) patients had segmental aneusomies including common microdeletion or microduplication syndromes and other genomic disorders. Chromosomal mosaicism was found in 12 (1.9%) neonates. CONCLUSIONS: Chromosomal microarray analysis is a valuable clinical diagnostic tool that allows precise and rapid identification of genomic imbalances and mosaic abnormalities as the cause of birth defects in neonates. Chromosomal microarray analysis allows for timely molecular diagnoses and detects many more clinically relevant genomic abnormalities than conventional cytogenetic studies, enabling more informed decision-making and management and appropriate assessment of recurrence risk.