Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight.

Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investigating molecular changes in muscle cells exposed to spaceflight that may mimic the underlying pathophysiology of sarcopenia. We report the results from three-dimensional myobundles derived from muscle biopsies from young and older adults, integrated into an autonomous CubeLab™, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analyses comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation. The analyses also revealed downregulated differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were downregulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides an approach to studying the cell autonomous effects of spaceflight on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. We also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLabTM payloads on the ISS.

Proportionate universalism intervention is effective for tackling nutritional social gradient in adolescents: the PRALIMAP-INÈS mixed randomised trial.

OBJECTIVE: This study aimed to investigate the effectiveness of proportionate universalism intervention to reduce the slope of the nutritional social gradient in adolescents. STUDY DESIGN: A mixed (experimental and quasi-experimental) multicentre trial. METHODS: Data from 985 adolescents of the PRALIMAP-INÈS trial (North-eastern France, 2012-2015) were analysed. For this, adolescents were split into five social classes according to the Family Affluence Scale: Highly Less Advantaged (H.L.Ad; n = 33), Less Advantaged (L.Ad; n = 155), Intermediate (Int; n = 404), Advantaged (Ad; n = 324) and Highly Advantaged (H.Ad; n = 69). The overweight care management was a standard care for all and a strengthened one adapted to the social class of adolescents. The main outcome was the 1-year change of the body mass index z-score (BMIz) slope. Other nutritional outcomes were BMI, ΔBMIp95 (BMI minus 95th percentile of the WHO reference), %BMIp95 (percent of 95th percentile of the WHO reference), leisure-time sport, consumption of fruits and vegetables and consumption of sugary foods and drinks. RESULTS: The inclusion data confirmed a weight social gradient expressed by a significant BMIz linear regression coefficient (ß = -0.09 [-0.14 to -0.04], P < 0.0001). The higher the social class, the lower the BMIz. The 1-year BMIz linear regression coefficient was -0.07 [-0.12 to -0.02], corresponding to a significant weight social gradient reduction of 23.3% (ß = 0.021 [0.001 to 0.041]; P = 0.04). Consistent results were found for other nutritional outcomes. CONCLUSIONS: PRALIMAP-INÈS shows that proportionate universalism intervention is effective to reduce the adolescents' nutritional social gradient and suggests that equitable health programmes and policies are a realistic goal.

Economic evaluation of a school-based strategy to prevent overweight and obesity in French adolescents: insights from the PRALIMAP randomised trial.

OBJECTIVES: This study aimed to provide cost-effectiveness and budget impact analyses of a school-based overweight/obesity screening and care prevention strategy among adolescents. STUDY DESIGN: Cost-effectiveness and budget impact analyses. METHODS: Data from 3538 adolescents who participated in a school-based randomised controlled trial in the Northeast of France were used. Costs (from a public payer's perspective) included screening for overweight and obesity and subsequent care. Effectiveness was measured as the change in body mass index (kilogram per square metre), prevalence of overweight/obesity, moderate physical activity energy expenditure, duration and frequency and total sitting time. The incremental cost-effectiveness ratio was calculated, and a budget impact analysis was conducted. RESULTS: The screening and care strategy resulted in an incremental cost-effectiveness ratio of €1634.48 per averted case of overweight/obesity and €255.43 per body mass index unit decrease. The costs for increasing moderate physical activity by 1000 metabolic equivalent of task-min/week, duration by 60 min/week and frequency 1 day/week were €165.28, €39.21 and €93.66 per adolescent, respectively. Decreasing total sitting time by 60 min/week had a cost of €8.49 per adolescent. The cost of implementing the strategy nationally was estimated to be €50.1 million with a payback period from 3.6 to 7.3 years. CONCLUSIONS: The screening and care strategy could be an efficient way to prevent overweight and obesity among adolescents. Future studies should investigate how the current results could be achieved in schools with different settings and thus justify its relevance for overweight and obesity prevention to policy-makers.

Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells.

Microphysiological systems (MPS), also referred to as tissue chips, incorporating 3D skeletal myobundles are a novel approach for physiological and pharmacological studies to uncover new medical treatments for sarcopenia. We characterize a MPS in which engineered skeletal muscle myobundles derived from donor-specific satellite cells that model aged phenotypes are encapsulated in a perfused tissue chip platform containing platinum electrodes. Our myobundles were derived from CD56+ myogenic cells obtained via percutaneous biopsy of the vastus lateralis from adults phenotyped by age and physical activity. Following 17 days differentiation including 5 days of a 3 V, 2 Hz electrical stimulation regime, the myobundles exhibited fused myotube alignment and upregulation of myogenic, myofiber assembly, signaling and contractile genes as demonstrated by gene array profiling and localization of key components of the sarcomere. Our results demonstrate that myobundles derived from the young, active (YA) group showed high intensity immunofluorescent staining of α-actinin proteins and responded to electrical stimuli with a ~1 µm displacement magnitude compared with non-stimulated myobundles. Myobundles derived from older sedentary group (OS) did not display a synchronous contraction response. Hypertrophic potential is increased in YA-derived myobundles in response to stimulation as shown by upregulation of insulin growth factor (IGF-1), α-actinin (ACTN3, ACTA1) and fast twitch troponin protein (TNNI2) compared with OS-derived myobundles. Our MPS mimics disease states of muscle decline and thus provides an aged system and experimental platform to investigate electrical stimulation mimicking exercise regimes and may be adapted to long duration studies of compound efficacy and toxicity for therapeutic evaluation against sarcopenia.

Finding gaps in routine TB surveillance activities in Bangladesh.

BACKGROUND: TB was the leading cause of death from a single infectious pathogen globally between 2014 and 2019. Fine-scale estimates of TB prevalence and case notifications can be combined to guide priority-setting for strengthening routine surveillance activities in high-burden countries. We produce policy-relevant estimates of the TB epidemic at the second administrative unit in Bangladesh.METHODS: We used a Bayesian spatial framework and the cross-sectional National TB Prevalence Survey from 2015-2016 in Bangladesh to estimate prevalence by district. We used case notifications to calculate prevalence-to-notification ratio, a key metric of under-diagnosis and under-reporting.RESULTS: TB prevalence rates were highest in the north-eastern districts and ranged from 160 cases per 100,000 (95% uncertainty interval [UI] 80-310) in Jashore to 840 (UI 690-1020) in Sunamganj. Despite moderate prevalence rates, the Rajshahi and Dhaka Divisions presented the highest prevalence-to-notification ratios due to low case notifications. Resolving subnational disparities in case detection could lead to 26,500 additional TB cases (UI 8,500-79,400) notified every year.CONCLUSION: This study is the first to produce and map subnational estimates of TB prevalence and prevalence-to-notification ratios, which are essential to target prevention and treatment efforts in high-burden settings. Reaching TB cases currently missing from care will be key to ending the TB epidemic.

Obesity phenotype and patient-reported outcomes in moderate and severe chronic kidney disease: a cross-sectional study from the CKD-REIN cohort study.

PURPOSE: To evaluate the association between obesity phenotypes and health-related quality of life (HRQoL) in non-dialysis-dependent CKD patients. METHODS: Data from the national CKD-REIN cohort which included 3033 patients with stage 3-4 CKD were used. Patients were divided into three groups: non-obese (NO) patients (BMI < 30 kg/m2), metabolically healthy obese (MHO) (BMI ≥ 30 kg/m2 and ≤ 1 criterion NCEP/ATP III), and metabolically unhealthy obese (MUO) (BMI ≥ 30 kg/m2 and ≥ 2 criteria NCEP/ATP III). HRQoL was measured by the KDQOL-36™ which comprised three disease-specific dimensions: symptoms, effects, and burden and two summaries scores: physical (PCS) and mental (MCS). We used a mixed effect model with adjustment on sociodemographic characteristics and comorbidities. RESULTS: A total of 2693 patients completed the self-administered questionnaires. MHO patients accounted for 3.4% of the cohort and for 12% of obese patients. In the NO group, average HRQoL scores were 77.2 ± 15.9 for symptoms, 83.5 ± 16.5 for effects, 76.8 ± 22.7 for burden, 43.5 ± 9.7 for PCS, and 47.9 ± 7.0 for MCS. In the multivariate analysis, scores were similar in MHO and NO patients, but significantly different with those in MUO patients: symptoms (- 0.7; p = 0.71 vs. - 3.0; p = 0.0025), effects (+ 1.2; p = 0.57 vs. - 4.3; p < 0.0001), burden (+ 2.7; p = 0.31 vs. - 3.6; p = 0.0031), and PCS (- 0.6; p = 0.58 vs. - 4.3; p < 0.0001). MCS was not associated with obesity phenotypes. CONCLUSIONS: This study demonstrated an association between obesity phenotypes and QoL in non-dialysis-dependent CKD patients. MUO patients had worse QoL than NO and MHO patients even after adjustment on comorbidities.