Saliva microRNA Biomarkers of Cumulative Concussion

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p \u3c 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p \u3c 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects

Refinement of Saliva MicroRNA Biomarkers for Sports-Related Concussion

Purpose 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 whether 40 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, miR-182-5p) decreased (adjusted p \u3c 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, miR-29c-3p) were associated (R \u3e 0.5; adjusted p \u3c 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 \u3c 0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (AUC \u3e 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

Diagnosing Mild Traumatic Brain Injury Using Saliva RNA Compared to Cognitive and Balance Testing

BACKGROUND: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance. METHODS: This case‐control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4‐7, 8‐14, 15‐30, and 31‐60 days post‐mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi‐interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. RESULTS: A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross‐validated area under the curve (AUC) of .857 in the training set (95% CI, .816‐.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post‐Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross‐validated AUC of .835 (95% CI, .782‐.880) and .853 (95% CI, .803‐.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845‐.925) as symptom burden and four ncRNAs (.932; 95% CI, .890‐.965). CONCLUSION: Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI

Déclin de la végétation aquatique submergée au lac Saint-Pierre de 2002 à 2021

La végétation aquatique submergée (VAS) joue plusieurs rôles écologiques cruciaux et offre des services écosystémiques inestimables aux sociétés humaines. Cependant, une tendance mondiale montre un déclin de la VAS, généralement causé par la hausse des matières en suspension et des nutriments dans l’eau. L’étude de la VAS du lac Saint-Pierre de 2002 à 2021 a permis de documenter l’occurrence et la composition en espèces de cette végétation. La probabilité d’observer de la VAS aux différentes stations d’échantillonnage est passée de 75 % en 2002 à 20 % en 2021. Ce déclin de la VAS est accompagné d’un changement de composition de la communauté végétale principalement attribuable à la diminution de la vallisnérie d’Amérique (Vallisneria americana). Un potentiel refuge photique associé à la masse d’eau translucide des Grands Lacs supporterait le développement de la VAS dans le lac Saint-Pierre. Toute intervention réduisant la dispersion de cette masse d’eau dans le lac Saint-Pierre devrait être évitée. Des actions de gestion visant l’amélioration de la qualité de l’eau du lac Saint-Pierre et ses tributaires, en réduisant notamment la turbidité, sont nécessaires afin de protéger et de restaurer cette réserve mondiale de la biosphère de l’UNESCO.Submerged aquatic vegetation (SAV) plays several crucial ecological roles and provides invaluable ecosystem services to humans. However, it is declining globally, principally due to an increase in the amount of suspended matter and nutrients within water bodies. A series of studies of the SAV in Lake Saint-Pierre (Québec, Canada) conducted between 2002 and 2021, documented changes in the occurrence and species composition of this vegetation type. The probability of observing SAV at the different sampling stations decreased from 75% in 2002 to 20% in 2021. This decline was accompanied by a change in species composition, mainly associated with a decrease in the amount of American eelgrass (Vallisneria americana). The clearer mass of water flowing from the Great Lakes possibly offers a photic refuge for SAV in Lake Saint-Pierre. Any intervention that would potentially reduce the dispersion of this water mass within the lake should be avoided. Management actions aimed at improving the water quality of Lake Saint-Pierre and its tributaries, notably by reducing turbidity, are needed to restore and protect this UNESCO World Biosphere Reserve

Freshwater Crayfish: A Potential Benthic-Zone Indicator of Nanosilver and Ionic Silver Pollution

Nowadays, silver nanoparticles (AgNPs) are utilized in numerous applications, raising justified concerns about their release into the environment. This study demonstrates the potential to use freshwater crayfish as a benthic-zone indicator of nanosilver and ionic silver pollution. Crayfish were acclimated to 20 L aquaria filled with Hudson River water (HRW) and exposed for 14 days to widely used Creighton AgNPs and Ag⁺ at doses of up to 360 μg L^–1 to surpass regulated water concentrations. The uptake and distribution of Ag in over 650 exoskeletons, gills, hepatopancreas and muscles samples were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) in conjunction with two complementary U.S. EPA-endorsed methods: the external calibration and the standard additions. Reflecting the environmental plasticity of the two investigated species, <i>Orconectes virilis</i> accumulated in a dose-dependent manner more Ag than <i>Procambarus clarkii</i> (on average 31% more Ag). Both species showed DNA damage and severe histological changes in the presence of Ag. However, Ag⁺ generally led to higher Ag accumulations (28%) and was more toxic. By the harvest day, about 14 ± 9% of the 360 μg L^–1 of AgNP exposure in the HRW oxidized to Ag⁺ and may have contributed to the observed toxicities and bioaccumulations. The hepatopancreas (1.5–17.4 μg of Ag g^–1 of tissue) was identified as the best tissue-indicator of AgNP pollution, while the gills (4.5–22.0 μg g^–1) and hepatopancreas (2.5–16.7 μg g^–1) complementarily monitored the presence of Ag⁺