Placing the keystone: the LIMBIC Military and Tactical Athlete Research Study.

OBJECTIVE: The LIMBIC Military and Tactical Athletic Research Study (MATARS) framework was established to confirm and extend understanding of concussion with initial studies driven by clinical data collected between 2015 and 2020 in a collegiate sports setting. The LIMBIC MATARS framework will be leveraged to apply gold-standard and innovative research designs to advance the science of concussion. This manuscript provides the background, methodology, and initial demographic data associated with the LIMBIC MATARS. METHODS: Consensus-based common data elements were used to conduct a retrospective chart review, specific to collegiate athletes diagnosed with concussions between 2015 and 2020 at 11 universities. RESULTS: A final sample of 1,311 (47.8% female) concussions were diagnosed during the five-year study period from athletes participating in a variety of National Collegiate Athlete Association (NCAA) sports. The LIMBIC MATARS demographic data, align with the NCAA and other pioneering multi-site concussion-related studies in terms of biological sex, race and ethnicity, and sport participation. CONCLUSION: This pragmatic, methodological approach was used to address several a priori hypotheses related to concussion, align with other multi-site studies of concussion, and establish a consortium for future investigations.

Racial identity and concussion diagnosis and recovery trajectories in collegiate athletes: a LIMBIC MATARS investigation.

OBJECTIVE: To determine if there were concussion diagnosis and recovery disparities between collegiate athletes with Black and White racial identities. DESIGN: Retrospective cohort study. METHODS: Concussion information was extracted from NCAA athlete medical files at LIMBIC MATARS member institutions from the 2015-16' to 2019-20' academic years. A total of 410 concussions from 9 institutions were included that provided all independent (i.e. racial identity of Black or White) and dependent variable information (i.e. dates of injury, diagnosis, symptom resolution, and return to sport) that were analyzed using Mann-Whitney U tests. The sample consisted of 114 (27.8%) concussions sustained by Black athletes and 296 (72.1%) sustained by White athletes. RESULTS: The overall sample had a median of 0 days between injury occurrence to diagnosis, 7 days to symptom resolution, and 12 days to return to sport. No significant timing differences were observed for concussion diagnosis (p = .14), symptom resolution (p = .39), or return to sport (p = 0.58) between collegiate athletes with Black versus White racial identities. CONCLUSIONS: These findings may reflect equitable access to onsite sports medicine healthcare resources that facilitate concussion management in the collegiate sport setting. Future work should explore these associations with a larger and more diverse sample of collegiate athletes.

Analysis of N- and O-linked protein glycosylation in children with Prader-Willi syndrome.

BACKGROUND: Current genotype-phenotype correlations in Prader-Willi syndrome (PWS) are struggling to give an explanation of the diversity in phenotype and there is a need to move towards a molecular understanding of PWS. A range of functions related to glycoproteins are involved in the pathophysiology of PWS and it may be that abnormal glycosylation is contributing to the biological phenotype. The objective of this study was to investigate the state of N- and O-linked glycosylation in children with Prader-Willi syndrome. METHODS: Twenty-three children with PWS and 20 non-PWS controls were included in the study. Protein N-linked glycosylation was assessed by analysing serum transferrin through mass spectrometry and protein O-linked through isoelectric focusing (IEF) of serum apolipoprotein C-III (apoC-III), confirmed by mass spectrometry. RESULTS: The results of this analysis indicated that the N-linked glycosylation pathway in PWS is normal. A subgroup of PWS individuals was found to have a hyposialylated pattern of apoC-III isoforms. This was independent of the underlying genetic mechanism and is the first report of an apoC-III IEF abnormality in PWS. CONCLUSIONS: This is the first report of apoC-III hyposialylation in PWS. As this field is in its infancy, additional study is required before these findings may be used in clinical settings.

Alanine in HI: a silent mutation cries out!

It is a widely held paradigm in molecular biology that a change in the third base of a codon is silent in terms of expression. In this investigation, results are presented that challenge that paradigm, at least in terms of one polymorphism in KCNJ11, which is one of five genes that have been implicated in the disorder Hyperinsulinism of Infancy. In two cohorts of Australian patients, an uneven distribution of KCNJ11 SNP's was observed. A silent polymorphism at codon 190 was over-represented in the patients who responded well to medical treatment and under-represented in those that required radical surgical intervention. In an attempt to investigate this polymorphism, it was expressed in vitro and western blot analysis showed that there were virtually no bands from the homozygous variant samples, while strong bands were seen in normal controls. The human genome is highly redundant in terms of tRNA species for each amino acids but enigmatically under-represents a number of specific codons. The polymorphism in question occurs within one such codon. We propose that the presence of a base change at the third position of codon that is not represented by a corresponding anti-codon within the human nuclear tRNA leads to a decreased rate of expression of the protein.