The Characteristic Response of the Human Leukocyte Transcriptome to 60 Days of Bed Rest and to Reambulation.

INTRODUCTION: We sought to isolate the microgravity effect of spaceflight from other space stressors by characterizing the leukocytes' transcriptome of participants to a 60-d bed rest study; an Earth model of microgravity. METHODS: Twenty healthy men received a nutritional supplement or not and 10 blood samples were collected throughout three study phases: baseline data collection (BDC) (BDC-12, BDC-11), head-down tilt (HDT) bed rest (HDT1, HDT2, HDT30, HDT60), and reambulation (R1, R2, R12, R30). We measured gene expression through RNA sequencing of leukocytes, applied generalized linear models to assess differential expression followed by enrichment analysis to identify temporal changes (model 1) and to measure the impact of a nutritional supplement (model 2). RESULTS: Baseline transcriptomes included 14,624 protein-coding transcripts and showed both high intraindividual correlations (mean Kendall coefficient, 0.91 ± 0.04) and interindividual homogeneity (0.89 ± 0.03). We identified 2415 differentially expressed protein-coding transcripts grouping into six clusters (C1-C6). At phase transitions, clusters showed either a decrease-then-increase (C3 and C5) or an increase-then-decrease (C1, C2, C6) pattern. All six clusters converged toward average expression at HDT30 and HDT60. Gene ontology terms at baseline related to immune functions while in bed rest and reambulation related to sequestration of ions, immune response, cellular stress, and mineralization. The nutritional intervention had no effect. CONCLUSIONS: The temporal profiles of leukocytes' transcriptomes emphasized the dynamic nature of gene expression occurring during and after bed rest. Enriched biological processes among the differentially expressed genes included immune related and unrelated responses. The convergence toward no differential expression at days 30 and 60 of bed rest suggests a hypometabolic state. Current findings can guide future work on the complex responses and adaptation mechanisms to microgravity.

Six degrees head-down tilt bed rest caused low-grade hemolysis: a prospective randomized clinical trial.

This study aimed to measure hemolysis before, during and after 60 days of the ground-based spaceflight analog bed rest and the effect of a nutritional intervention through a prospective randomized clinical trial. Twenty male participants were hospitalized for 88 days comprised of 14 days of ambulatory baseline, 60 days of 6° head-down tilt bed rest and 14 days of reambulation. Ten participants each received a control diet or daily polyphenol associated with omega-3, vitamin E, and selenium supplements. The primary outcome was endogenous carbon monoxide (CO) elimination measured by gas chromatography. Hemolysis was also measured with serial bilirubin, iron, transferrin saturation blood levels and serial 3-day stool collections were used to measure urobilinoid excretion using photometry. Total hemoglobin mass (tHb) was measured using CO-rebreathing. CO elimination increased after 5, 11, 30, and 57 days of bed rest: +289 ppb (95% CI 101-477 ppb; p = 0.004), +253 ppb (78-427 ppb; p = 0.007), +193 ppb (89-298 ppb; p = 0.001) and +858 ppb (670-1046 ppb; p < 0.000), respectively, compared to baseline. Bilirubin increased after 20 and 49 days of bed rest +0.8 mg/l (p = 0.013) and +1.1 mg/l (p = 0.012), respectively; and iron increased after 20 days of bed rest +10.5 µg/dl (p = 0.032). The nutritional intervention did not change CO elimination. THb was lower after 60 days of bed rest -0.9 g/kg (p = 0.001). Bed rest enhanced hemolysis as measured through all three by-products of heme oxygenase. Ongoing enhanced hemolysis over 60 days contributed to a 10% decrease in tHb mass. Modulation of red blood cell control towards increased hemolysis may be an important mechanism causing anemia in astronauts.

Marrow adipose tissue gradient is preserved through high protein diet and bed rest. A randomized crossover study.

CONTEXT: Marrow adipose tissue (MAT) has a peripheral to central distribution in adults, higher in peripheral bones. Similarly, the spine has a caudal to cephalad MAT distribution, higher in lumbar vertebras. Diet and the level of physical activities are known modulators of MAT with significant impact on bone; however, whether these can modulate the MAT gradient is unknown. OBJECTIVE: To measure the effect of high protein diet and bed rest interventions on the lumbar MAT gradient. DESIGN PARTICIPANTS INTERVENTION: In a prospective randomized crossover trial, 10 healthy men participated in 2 consecutive campaigns of 21days head-down-tilt-bed-rest (HDTBR). They received either whey protein and potassium bicarbonate-supplemented or control diet separated by a 4-month washout period. MAIN OUTCOME MEASURES: Ten serial MRI measures of lumbar vertebral fat fraction (VFF) were performed at baseline, 10days and 20days of HDTBR and 3 and 28days after HDTBR of each bed rest campaign. RESULTS: The mean L5-L1 VFF difference of 4.2 ± 1.2 percentage point higher at L5 (p = 0.008) constituted a caudal to cephalad lumbar MAT gradient. High protein diet did not alter the lumbar VFF differences during both HDTBR campaigns (all time points p > 0.05). Similarly, 2 campaigns of 21days of HDTBR did not change the lumbar VFF differences (all time points p > 0.05). CONCLUSIONS: This pilot study established that the lumbar vertebral MAT gradient was not altered by a high protein nor by 2 × 21days bed rest interventions. These findings demonstrated that this lack of mechanical stimulus was not an important modulator of the lumbar MAT gradient. The highly preserved MAT gradient needs to be measured in more situations of health and disease and may potentially serve to detect pathological situations.

Impact of pleasure-oriented messages on food choices: is it more effective than traditional health-oriented messages to promote healthy eating?

Some authors have suggested that eating pleasure is underused to promote healthy eating. However, little is known about the potential of pleasure-oriented messages to lead to healthier food choices. The aim of this study was to examine the effects of pleasure- and health-oriented messages on food choices made from a buffet. One hundred and ninety-eight participants (50% women), unaware of the real objective of the study, were randomized in three groups: 1) pleasure, 2) health, and 3) control. They first completed three 24 h food recalls to assess their overall diet quality using the Canadian Healthy Eating Index (C-HEI; score: 0 to 100). Thereafter, participants came to the research institute and those randomized in the "pleasure" and "health" groups read a leaflet on healthy eating, using either a pleasure or a health orientation respectively. Participants in the control group had no leaflet to read. All participants had subsequently to choose four food items in a buffet offering both healthy and unhealthy foods. Results showed a group by diet quality interaction (p = 0.02). Among participants with lower diet quality (C-HEI score below 50), those in the pleasure and health groups were more likely than participants in the control group to choose a healthier main course (prevalence ratios (PR) 1.71, 95% CI 1.12-2.62 and 1.83, 95% CI 1.21-2.77 for the pleasure and health group respectively) and a healthier beverage (PR 1.67, 95% CI 1.02-2.71 and 1.66, 95% CI 1.02-2.72, respectively). No such effect was observed among participants with higher C-HEI scores. In conclusion, our results suggest that in people with sub-optimal dietary habits, pleasure-oriented messages and traditional health messages are both useful to favor healthy main course and beverage choices.

Optimising conservative management of chronic low back pain: study protocol for a randomised controlled trial.

BACKGROUND: Lower back pain is a global health issue affecting approximately 80% of people at some stage in their life. The current literature suggests that any exercise is beneficial for reducing back pain. However, as pain is a subjective evaluation and physical deficits are evident in low back pain, using it as the sole outcome measure to evaluate superiority of an exercise protocol for low back pain treatment is insufficient. The overarching goal of the current clinical trial is to implement two common, conservative intervention approaches and examine their impact on deficits in chronic low back pain. METHODS/DESIGN: Forty participants, 25-45 years old with chronic (>3 months), non-specific low back pain will be recruited. Participants will be randomised to receive either motor control and manual therapy (n = 20) or general strength and conditioning (n = 20) exercise treatments for 6 months. The motor control/manual therapy group will receive twelve 30-min sessions, ten in the first 3 months (one or two per week) and two in the last 3 months. The general exercise group will attend two 1-hour sessions weekly for 3 months, and one or two a week for the following 3 months. Primary outcome measures are average lumbar spine intervertebral disc T2 relaxation time and changes in thickness of the transversus abdominis muscle on a leg lift using magnetic resonance imaging (MRI). Secondary outcomes include muscle size and fat content, vertebral body fat content, intervertebral disc morphology and water diffusion measured by MRI, body composition using dual energy X-ray absorptiometry, physical function through functional tests, changes in corticospinal excitability and cortical motor representation of the spinal muscles using transcranial magnetic stimulation and self-reported measure of pain symptoms, health and disability. Outcome measures will be conducted at baseline, at the 3-month follow-up and at 6 months at the end of intervention. Pain, depressive symptomology and emotions will be captured fortnightly by questionnaires. DISCUSSION: Chronic low back pain is ranked the highest disabling disorder in Australia. The findings of this study will inform clinical practice guidelines to assist with decision-making approaches where outcomes beyond pain are sought for adults with chronic low back pain. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615001270505 . Registered on 20 November 2015.