So Different, yet So Similar: Meta-Analysis and Policy Modeling of Willingness to Participate in Clinical Trials among Brazilians and Indians

BACKGROUND: With the global expansion of clinical trials and the expectations of the rise of the emerging economies known as BRICs (Brazil, Russia, India and China), the understanding of factors that affect the willingness to participate in clinical trials of patients from those countries assumes a central role in the future of health research. METHODS: We conducted a systematic review and meta-analysis (SRMA) of willingness to participate in clinical trials among Brazilian patients and then we compared it with Indian patients (with results of another SRMA previously conducted by our group) through a system dynamics model. RESULTS: Five studies were included in the SRMA of Brazilian patients. Our main findings are 1) the major motivation for Brazilian patients to participate in clinical trials is altruism, 2) monetary reimbursement is the least important factor motivating Brazilian patients, 3) the major barrier for Brazilian patients to not participate in clinical trials is the fear of side effects, and 4) Brazilian patients are more likely willing to participate in clinical trials than Indians. CONCLUSION: Our study provides important insights for investigators and sponsors for planning trials in Brazil (and India) in the future. Ignoring these results may lead to unnecessary fund/time spending. More studies are needed to validate our results and for better understanding of this poorly studied theme

Microglial brain region−dependent diversity and selective regional sensitivities to aging

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration

Performance, complexity and dynamics of force maintenance and modulation in young and older adults

International audienceThe present study addresses how task constraints and aging influence isometric force control. We used two tasks requiring either force maintenance (straight line target force) or force modulation (sine-wave target force) around different force levels and at different modulation frequencies. Force levels were defined relative the individual maximum voluntary contraction. A group of young adults (mean age ± SD = 25 ± 3.6 years) and a group of elderly (mean age = 77 ± 6.4 years) took part in the study. Age-and task-related effects were assessed through differences in: (i) force control accuracy, (ii) time-structure of force fluctuations, and (iii) the contribution of deterministic (predictable) and stochastic (noiselike) dynamic components to the expressed behavior. Performance-wise, the elderly showed a pervasive lower accuracy and higher variability than the young participants. The analysis of fluctuations showed that the elderly produced force signals that were less complex than those of the young adults during the maintenance task, but the reverse was observed in the modulation task. Behavioral complexity results suggest a reduced adaptability to task-constraints with advanced age. Regarding the dynamics, we found comparable generating mechanisms in both age groups for both tasks and in all conditions, namely a fixed-point for force maintenance and a limit-cycle for force modulation. However, aging increased the stochasticity (noise-driven fluctuations) of force fluctuations in the cyclic force modulation, which could be related to the increased complexity found in elderly for this same task. To our knowledge this is the first time that these different perspectives to motor control are used simultaneously to characterize force control capacities. Our findings show their complementarity in revealing distinct aspects of sensorimotor adaptation to task constraints and age-related declines. Although further research is still needed to identify the physiological underpinnings, the used task and methodology are shown to have both fundamental and clinical applications