Refinement of saliva microRNA biomarkers for sports-related concussion

Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.

Compact nano-void spectrometer based on a stable engineered scattering system

Random scattering of light in disordered media can be used for highly sensitive speckle-based wavemeters and spectrometers. However, the multiple scattering events that fold long optical paths within a compact space also make such devices exceedingly sensitive to vibrations and small disturbances to the disordered media. Here, we show how scattering can be engineered so that it can be used for a compact computational spectrometer that is largely insensitive to environmental factors. We designed and fabricated a three-dimensional pseudo-random nano-void pattern with 62% scattering efficiency. The controlled amount of multiple scattering ensured a sufficiently long optical path for the target resolution of 100 pm, with optimal long-term stability. The 200-μm-thick scattering silica substrate was integrated in a compact assembly with a low-cost camera sensor. The target resolution was achieved for full spectrum measurements while single wavelengths could be determined with 50 pm resolution. Such tailored scattering systems can improve the trade-off among cost, size, stability, and spectral resolution in computational spectrometers.