History of concussion and lowered heart rate variability at rest beyond symptom recovery:a systematic review and meta-analysis

Introduction: Concussion is a growing concern in worldwide sporting culture. Heart rate variability (HRV) is closely tied with autonomic nervous system (ANS) deficits that arise from a concussion. The objective of this review was to determine if a history of concussion (HOC) can impact HRV values in the time-domain in individuals at rest. This review works to add to the literature surrounding HRV testing and if it can be used to check for brain vulnerabilities beyond the recovery of concussion symptoms. Materials and methods: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. A computer based systematic review scanned articles dating from 1996 to June 2023 through PubMed, Cochrane Library, Google Scholar, and EMBASE databases. A risk of bias assessment was conducted using the ROBINS-E tool. The average difference in time between heartbeats (MeanNN), the standard deviation of the differences (SDNN), and the root mean squared of the successive intervals (RMSSD) were measured. Results: Six total studies were found that fit the inclusion criteria including a total of 242 participants (133 without HOC, 109 with HOC). The average age of the control group was 23.3 ± 8.2, while the average age of the history of TBI group was 25.4 ± 9.7, with no significant difference between the groups (p = 0.202). Four of the studies reported no significant difference in any of the three measures, while two of the studies reported significant difference for all three measures. The meta-analysis was conducted and found that MeanNN (p = 0.03) and RMSSD (p = 0.04) reached statistical significance, while SDNN did not (p = 0.11). Conclusion: The results of this meta-analysis showed significant difference in two of the three HRV time-domain parameters evaluated. It demonstrates that there can be lowered HRV values that expand beyond the recovery of symptoms, reflecting an extensive period of ANS susceptibility after a concussion. This may be an important variable in determining an athlete’s return to play (RTP). Lack of homogenous study populations and testing methods introduces potential for bias and confounding factors, such as gender or age. Future studies should focus on baseline tests to compare individuals to themselves rather than matched controls

History of concussion and lowered heart rate variability at rest beyond symptom recovery: a systematic review and meta-analysis

IntroductionConcussion is a growing concern in worldwide sporting culture. Heart rate variability (HRV) is closely tied with autonomic nervous system (ANS) deficits that arise from a concussion. The objective of this review was to determine if a history of concussion (HOC) can impact HRV values in the time-domain in individuals at rest. This review works to add to the literature surrounding HRV testing and if it can be used to check for brain vulnerabilities beyond the recovery of concussion symptoms.Materials and methodsThe systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. A computer based systematic review scanned articles dating from 1996 to June 2023 through PubMed, Cochrane Library, Google Scholar, and EMBASE databases. A risk of bias assessment was conducted using the ROBINS-E tool. The average difference in time between heartbeats (MeanNN), the standard deviation of the differences (SDNN), and the root mean squared of the successive intervals (RMSSD) were measured.ResultsSix total studies were found that fit the inclusion criteria including a total of 242 participants (133 without HOC, 109 with HOC). The average age of the control group was 23.3 ± 8.2, while the average age of the history of TBI group was 25.4 ± 9.7, with no significant difference between the groups (p = 0.202). Four of the studies reported no significant difference in any of the three measures, while two of the studies reported significant difference for all three measures. The meta-analysis was conducted and found that MeanNN (p = 0.03) and RMSSD (p = 0.04) reached statistical significance, while SDNN did not (p = 0.11).ConclusionThe results of this meta-analysis showed significant difference in two of the three HRV time-domain parameters evaluated. It demonstrates that there can be lowered HRV values that expand beyond the recovery of symptoms, reflecting an extensive period of ANS susceptibility after a concussion. This may be an important variable in determining an athlete’s return to play (RTP). Lack of homogenous study populations and testing methods introduces potential for bias and confounding factors, such as gender or age. Future studies should focus on baseline tests to compare individuals to themselves rather than matched controls

Metastases risk in thin cutaneous melanoma: Prognostic value of clinical-pathologic characteristics and mutation profile

Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases. Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases. Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations. Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness < 0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases

A role for talin in presynaptic function

Talin, an adaptor between integrin and the actin cytoskeleton at sites of cell adhesion, was recently found to be present at neuronal synapses, where its function remains unknown. Talin interacts with phosphatidylinositol-(4)-phosphate 5-kinase type Iγ, the major phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]–synthesizing enzyme in brain. To gain insight into the synaptic role of talin, we microinjected into the large lamprey axons reagents that compete the talin–PIP kinase interaction and then examined their effects on synaptic structure. A dramatic decrease of synaptic actin and an impairment of clathrin-mediated synaptic vesicle endocytosis were observed. The endocytic defect included an accumulation of clathrin-coated pits with wide necks, as previously observed after perturbing actin at these synapses. Thus, the interaction of PIP kinase with talin in presynaptic compartments provides a mechanism to coordinate PI(4,5)P2 synthesis, actin dynamics, and endocytosis, and further supports a functional link between actin and clathrin-mediated endocytosis

Translating Material Science into Bone Regenerative Medicine Applications: State-of-The Art Methods and Protocols

In the last 20 years, bone regenerative research has experienced exponential growth thanks to the discovery of new nanomaterials and improved manufacturing technologies that have emerged in the biomedical field. This revolution demands standardization of methods employed for biomaterials characterization in order to achieve comparable, interoperable, and reproducible results. The exploited methods for characterization span from biophysics and biochemical techniques, including microscopy and spectroscopy, functional assays for biological properties, and molecular profiling. This review aims to provide scholars with a rapid handbook collecting multidisciplinary methods for bone substitute R&amp;D and validation, getting sources from an up-to-date and comprehensive examination of the scientific landscape

Serum miR-502: A potential biomarker in the diagnosis of concussion in a pilot study of patients with normal structural brain imaging

Establishing a diagnosis of concussion within the context of competitive sport is frequently difficult due to the heterogeneity of presentation. Over the years, many endogenous proteins, including the recent Food and Drug Administration approved for mild-to-moderate traumatic brain injury, glial fibrillary acid protein and ubiquitin carboxy-terminal hydrolase, have been studied as potential biomarkers for the diagnosis of mild traumatic brain injury. Recently, a new class of potential biomarkers, the microRNAs, has shown promise as indicators of traumatic brain injury. In this pilot study, we have analysed the ability of pre-validated serum microRNAs (mi-425-5p and miR-502) to diagnose concussion, in cases without structural pathology. Their performance has been assessed alongside a set of identified protein biomarkers for traumatic brain injury in cohort of 41 concussed athletes. Athletes with a confirmed concussion underwent blood sampling after 48 h from concussion along with magnetic resonance imaging. Serum mi-425-5p and miR-502 were analysed by quantitative reverse transcription polymerase chain reaction, and digital immunoassay was used to determine serum concentrations of ubiquitin carboxy-terminal hydrolase, glial fibrillary acid protein, neurofilament light and Tau. Results were matched with 15 healthy volunteers. No structural/haemorrhagic pathology was identified. Protein biomarkers demonstrated variability among groups reflecting previous performance in the literature. Neurofilament light was the only marker to positively correlate with symptoms reported and SCAT5 scores. Despite the sub optimal timing of sampling beyond the optimal window for many of the protein biomarkers measured, miR-502 was significantly downregulated at all time points within a week form concussion ictus, showing a diagnostic sensitivity in cases beyond 48 h and without structural pathology