Effect of 6-Month Exercise Training on Neurovascular Function in Spinal Cord Injury.

INTRODUCTION: Although previous data show exacerbated incidence of cognitive impairment after spinal cord injury (SCI), the physiology that underlies this postinjury cognitive decline is unknown. One potential culprit is impairment in the ability of cerebral vasculature to alter regional flow to sustain neural metabolism (i.e., "neurovascular coupling"). We hypothesized that cerebrovascular responses to a working memory task are impaired in individuals with SCI and can be improved by aerobic exercise training. METHODS: We assessed the effect of injury and 6-month full-body aerobic exercise training on the cerebral blood flow response to cognitive demand (i.e., neurovascular coupling) in 24 individuals with SCI and 16 controls. Cognitive demand was introduced in a graded fashion using a working memory task. RESULTS: Reaction time tended to be higher in individuals with SCI, especially those with high-level (≥T4) injuries, possibly due to upper motor impairments. Neurovascular coupling was graded across task difficulty (P < 0.01) and followed cognitive demand, and injury itself did not have a significant effect (group effect P = 0.99, interaction P = 0.70). Individuals with low-level injuries (

Inconsistent relation of nonlinear heart rate variability indices to increasing vagal tone in healthy humans.

BACKGROUND: Prior work has found that linear heart rate variability (HRV) indices do not accurately reflect cardiac vagal control, and nonlinear indices of HRV have been proposed as alternative tools that may better capture cardiac vagal effects. We used progressive low dose atropine to induce changes in cardiac vagal tone to test the hypotheses that nonlinear HRV indices accurately reflect cardiac vagal control, and that their changes in response to low dose atropine correlate with those in RR interval. METHODS: Changes in RR interval and HRV indices during intravenous injections of saline (control) and 6 cumulative doses of atropine (from 1.4 to 7.2 µg/kg) during controlled breathing at 15 breaths per minute were assessed in 14 young healthy individuals. RESULTS: As expected, low dose atropine increased average RR interval (vagotonic effect). There was no strong association between vagotonic changes in RR interval and the majority of nonlinear HRV indices, either within or among subjects. CONCLUSIONS: These data suggest an inconsistent relationship between responses of nonlinear HRV indices and RR interval to changes in cardiac vagal tone. Therefore, nonlinear HRV indices may not be reliable indices of cardiac vagal control in healthy humans.

Differing epidemiological dynamics of Chikungunya virus in the Americas during the 2014-2015 epidemic.

Chikungunya virus (CHIKV) has been detected sporadically since the 1950s and includes three distinct co-circulating genotypes. In late 2013, the Asian genotype of CHIKV was responsible for the Caribbean outbreak (CO) that rapidly became an epidemic throughout the Americas. There is a limited understanding of the molecular evolution of CHIKV in the Americas during this epidemic. We sequenced 185 complete CHIKV genomes collected mainly from Nicaragua in Central America and Florida in the United States during the 2014-2015 Caribbean/Americas epidemic. Our comprehensive phylogenetic analyses estimated the epidemic history of the Asian genotype and the recent Caribbean outbreak (CO) clade, revealed considerable genetic diversity within the CO clade, and described different epidemiological dynamics of CHIKV in the Americas. Specifically, we identified multiple introductions in both Nicaragua and Florida, with rapid local spread of viruses in Nicaragua but limited autochthonous transmission in Florida in the US. Our phylogenetic analysis also showed phylogeographic clustering of the CO clade. In addition, we identified the significant amino acid substitutions that were observed across the entire Asian genotype during its evolution and examined amino acid changes that were specific to the CO clade. Deep sequencing analysis identified specific minor variants present in clinical specimens below-consensus levels. Finally, we investigated the association between viral phylogeny and geographic/clinical metadata in Nicaragua. To date, this study represents the largest single collection of CHIKV complete genomes during the Caribbean/Americas epidemic and significantly expands our understanding of the emergence and evolution of CHIKV CO clade in the Americas.

The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.

While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). Symptom burden was assessed using the Post-Concussion Symptom Scale. Subsequently, we explored the relationship between vasoreactivity and the severity of post-concussion headache and cognitive difficulties by linear models. During rebreathing, CO2 increased from 32.6 ± 1.6 to 46.8 ± 1.8 mmHg and cerebrovascular conductance (i.e., flow velocity over pressure) increased from 0.48 ± 0.04 to 0.74 ± 0.06 cms-1 mmHg-1. There was a strong linear relationship between the increase in CO2 and in conductance (R2 = 0.81 ± 0.05; p < 0.05). On average, cerebral vasoreactivity was 0.018 ± 0.003 cm-1 s-1 mmHg CO2-1. Although vasoreactivity tended to be somewhat higher in the asymptotic participants (0.019 ± 0.003 vs. 0.015 ± 0.005 cm-1 s-1 mmHg CO2-1), this difference was not statistically significant (p = 0.48). Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.

Introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations.

UNLABELLED: The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus--A/sw/Saskatchewan/02903/2009(H3N2)--has likely circulated undetected in swine for at least 7 years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931 to 2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least 1 year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, suggesting an association between the acquisition of swine-origin internal genes via reassortment and the adaptation of human influenza viruses to new swine hosts. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multihost ecology of influenza and the disease threats that swine and humans pose to each other. IMPORTANCE: The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus evolves in these animals hosts. While the importance of reassortment in generating genetically diverse influenza viruses in swine is well documented, the role of human-to-swine transmission has not been as intensively studied. Through a large-scale sequencing effort, we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least 7 years. In addition, we demonstrate that human-to-swine transmission has occurred frequently on a global scale over the past decades but that there is little persistence of human virus internal gene segments in swine.