Observations from a prospective small cohort study suggest that CGRP genes contribute to acute posttraumatic headache burden after concussion

Introduction: Post-traumatic headache (PTH) is commonly reported after concussion. Calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of migraine. We explored how single nucleotide polymorphisms (SNPs) from CGRP-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) related to headache burden during the first week after concussion. Methods: A prospective study was performed in 34 collegiate athletes who sustained a concussion. Participants completed the symptom evaluation checklist from the SCAT3 within 48 h of injury (V1), and again 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0–6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were reported and summed to calculate the headache burden. A saliva sample was obtained and genotyped for CALCA (rs3781719) and RAMP1 (rs10185142). RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) were dichotomized (A+, A- and T+, T-, respectively), and concatenated (T+A+, T+A-, T-A+, T-A-) for analyses. Results: Headache Burden at Visit 1 was greatest in T+A+ compared to T-A+, and trended toward a significant difference with T+A-. Repeated-measures ANOVA revealed the presence of significant visit main effects (p < 0.001, η2 = 0.404), but the group (p = 0.055) and interaction effects only trended (p = 0.094). Pearson's χ2-tests revealed that 88% of those with return-to play (RTP) exclusions ≥15 days had PTH with multi-sensory symptoms (PTH+SENS) as compared to 35% in those with RTP < 14 day. Conclusion: Knowledge of RAMP1 and CALCA genotypes appear to improve an understanding the presenting features and magnitude of headache burden after concussion injury

Strong mitochondrial DNA support for a Cretaceous origin of modern avian lineages

<p>Abstract</p> <p>Background</p> <p>Determining an absolute timescale for avian evolutionary history has proven contentious. The two sources of information available, paleontological data and inference from extant molecular genetic sequences (colloquially, 'rocks' and 'clocks'), have appeared irreconcilable; the fossil record supports a Cenozoic origin for most modern lineages, whereas molecular genetic estimates suggest that these same lineages originated deep within the Cretaceous and survived the K-Pg (Cretaceous-Paleogene; formerly Cretaceous-Tertiary or K-T) mass-extinction event. These two sources of data therefore appear to support fundamentally different models of avian evolution. The paradox has been speculated to reflect deficiencies in the fossil record, unrecognized biases in the treatment of genetic data or both. Here we attempt to explore uncertainty and limit bias entering into molecular divergence time estimates through: (i) improved taxon (<it>n </it>= 135) and character (<it>n = </it>4594 bp mtDNA) sampling; (ii) inclusion of multiple cladistically tested internal fossil calibration points (<it>n </it>= 18); (iii) correction for lineage-specific rate heterogeneity using a variety of methods (<it>n </it>= 5); (iv) accommodation of uncertainty in tree topology; and (v) testing for possible effects of episodic evolution.</p> <p>Results</p> <p>The various 'relaxed clock' methods all indicate that the major (basal) lineages of modern birds originated deep within the Cretaceous, although temporal intraordinal diversification patterns differ across methods. We find that topological uncertainty had a systematic but minor influence on date estimates for the origins of major clades, and Bayesian analyses assuming fixed topologies deliver similar results to analyses with unconstrained topologies. We also find that, contrary to expectation, rates of substitution are not autocorrelated across the tree in an ancestor-descendent fashion. Finally, we find no signature of episodic molecular evolution related to either speciation events or the K-Pg boundary that could systematically mislead inferences from genetic data.</p> <p>Conclusion</p> <p>The 'rock-clock' gap has been interpreted by some to be a result of the vagaries of molecular genetic divergence time estimates. However, despite measures to explore different forms of uncertainty in several key parameters, we fail to reconcile molecular genetic divergence time estimates with dates taken from the fossil record; instead, we find strong support for an ancient origin of modern bird lineages, with many extant orders and families arising in the mid-Cretaceous, consistent with previous molecular estimates. Although there is ample room for improvement on both sides of the 'rock-clock' divide (e.g. accounting for 'ghost' lineages in the fossil record and developing more realistic models of rate evolution for molecular genetic sequences), the consistent and conspicuous disagreement between these two sources of data more likely reflects a genuine difference between estimated ages of (i) stem-group origins and (ii) crown-group morphological diversifications, respectively. Further progress on this problem will benefit from greater communication between paleontologists and molecular phylogeneticists in accounting for error in avian lineage age estimates.</p

Concussion History and Heart Rate Variability During Bouts of Acute Stress

Context After a sport-related concussion, many athletes experience persisting neurophysiological alterations. These alterations may be absent at rest but emerge during moments of physiological stress. Unnoticed and untreated neurophysiological dysfunction may negatively affect long-term neurologic health in adolescent athletes, as they are at a critical point in development. Objective To assess cardio-autonomic functioning in athletes with and those without a history of concussion by quantifying measures of heart rate variability (HRV) during times of physical and mental exertion. Design Case-control study. Setting Research laboratory. Patients or Other Participants Thirty-four male Hockey Quebec Midget-AAA hockey players were separated into those with (n = 16; age = 16.06 ± 0.73 years, body mass index = 23.29 ± 1.79) and those without (n = 18; age = 15.98 ± 0.62 years, body mass index = 23.60 ± 2.49) a history of concussion. Intervention(s) All athletes underwent a series of HRV recording sessions (1) at rest, (2) while completing a cognitive task at rest, and (3) while completing a cognitive task after a bout of submaximal aerobic exercise. Main Outcome Measure(s) Time-domain measures of HRV, including mean NN intervals, SD of NN intervals, and root mean square of successive NN interval differences, were quantified for each assessment. Results No differences in characteristics were evident between groups. No between-groups differences in HRV at rest were observed. However, during the cognitive task at rest and after aerobic exercise, athletes with a history of concussion demonstrated a higher SD of NN intervals (78.1 ± 4.3 versus 63.2 ± 4.1 milliseconds and 71.2 ± 4.3 versus 65.2 ± 3.8 milliseconds, respectively; F1,31 = 4.31, P = .046) and root mean square of successive NN interval differences (75.8 ± 6.0 versus 59.0 ± 5.6 milliseconds and 74.0 ± 5.5 versus 59.0 ± 5.2 milliseconds, respectively; F1,31 = 4.88, P = .04) than athletes without a history of concussion. Conclusions Concussive injuries may result in long-term cardio-autonomic dysfunction. These deficits may not be present at rest but may be triggered by physiological stress

Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI).One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package.Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01) and 112±8 mg/dl (p<0.05), respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05) and 55±4 μmol/l (p<0.05)]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group.Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction