Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care.

BACKGROUND: An underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life. METHODS: Fifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48-72 h prior to each chemotherapy treatment and will perform 30-60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival. DISCUSSION: The DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03795493 , registered 7 January, 2019.

A post-exercise facilitation of executive function is independent of aerobically supported metabolic costs.

A single-bout of aerobic or resistance training facilitates executive function and is a benefit thought to be specific to exercise durations greater than 20 min. We sought to determine whether an executive benefit is observed for a session as brief as 10-min, and whether distinct and participant-specific exercise intensities - and associated metabolic costs - influence the magnitude of the benefit. Participants completed exercise sessions - via cycle ergometer - at moderate (80% of lactate threshold [LT]), heavy (15% of the difference between LT and VO2 peak) and very-heavy (50% of the difference between LT and VO2 peak) intensities determined via an incremental ramp test to volitional exhaustion. Pre- and post-exercise executive function was examined via antisaccades - an executive task requiring a saccade mirror-symmetrical to a visual stimulus. Antisaccades are an ideal tool for examining post-exercise executive changes due to the resolution of eye-tracking and because the task is mediated via the same frontoparietal networks as modified following single-bout and chronic exercise. A non-executive prosaccade task (i.e., saccade to veridical target location) was also completed to determine if the putative post-exercise benefit was specific to executive function. Results showed a 20 ms reduction in pre- to post-exercise antisaccade RTs (p < .02) and was independent of exercise intensity, whereas no such change was observed for prosaccades (p = .14). Furthermore, the antisaccade benefit occurred without concomitant changes in directional errors or endpoint accuracy; that is, participants did not decrease their post-exercise RTs at the cost of increased planning and execution errors (ps > 0.34). Accordingly, we propose that an exercise duration as brief as 10-min provides a reliable benefit to executive function and is an effect observed across the continuum of moderate to very-heavy intensities.

Improvement of enzyme transport in wood chips for thermomechanical pulp refining.

Wood chips, macerated wood chips and coarse wood fibers were compressed and allowed to decompress in enzyme solutions prior to mechanical refining. Electrical consumption in refining was monitored in order to investigate potential energy savings during refining. Wood treated with Celluclast(®) 1.5L showed a reduction in refining energy up to a 36%. Canadian Standard Freeness was used to track degree of refining. Decompressing in the enzyme solution gave a 15% reduction in energy consumption compared to having the already decompressed substrate treated with enzymes. This indicated that improving the transportation of enzymes into wood chips would further enhance the enzyme effect on refining. In this study, confocal laser scanning microscopy (CLSM) was used to track a dyed dextran of 70k molecular weight (the size of some of the larger enzymes) which was used as molecular probe to investigate the potential added penetration of enzymes induced by compression/decompression in the selected chip sizes.