A prospective study of physician-observed concussion during a varsity university hockey season: Metabolic changes in ice hockey players. Part 4 of 4

Object: Despite negative neuroimaging findings using traditional neuroimaging methods such as MRI and CT, sports-related concussions have been shown to cause neurometabolic changes in both the acute and subacute phases of head injury. However, no prospective clinical study has used an independent physician-observer design in the monitoring of these changes. The objective of this study was to evaluate the effects of repetitive concussive and subconcussive head impacts on neurometabolic concentrations in a prospective study of two Canadian Interuniversity Sports (CIS) ice hockey teams using MR spectroscopy (MRS). Methods: Forty-five ice hockey players (25 men and 20 women) participated in this study. All participants underwent pre- and postseason MRI, including spectroscopy imaging, using a 3-T MRI machine. The linear combination model was used to quantify the following ratios: glutamate/creatine-phosphocreatine (Cr), myoinositol/Cr, and N-acetylaspartate (NAA)/Cr. Individuals sustaining a medically diagnosed concussion were sent for MRI at 72 hours, 2 weeks, and 2 months after injury. Results: No statistically significant differences were observed between athletes who were diagnosed with a concussion and athletes who were not clinically diagnosed as sustaining a concussion. Although no statistically significant longitudinal metabolic changes were observed among athletes who were diagnosed with a concussion, the results demonstrated a predictable pattern of initial impairment, followed by a gradual return to ratios that were similar to, but lower than, baseline ratios. No significant pre- to postseason changes were demonstrated among men who were not observed to sustain a concussion. However, a substantively significant decrease in the NAA/Cr ratio was noted among the female hockey players (t(13) = 2.58, p = 0.02, ζ2 = 0.34). Conclusions: A key finding in this study, from the standpoint of future research design, is the demonstration of substantively significant metabolic changes among the players who were not diagnosed with a concussion. In addition, it may explain why there are few statistically significant differences demonstrated between players who were diagnosed with a concussion and players who were not diagnosed with a concussion (that is, the potency of the independent variable was diminished by the fact that the group of players not diagnosed with a concussion might be better described as a subgroup of the players who may have sustained a concussion but were not observed and diagnosed with a concussion). This result suggests that definitions of concussion may need to be revisited within sports with high levels of repetitive subconcussive head impacts. Future analysis of these data will examine the relationships between the modes of MRI (diffusion tensor imaging, MRS, and susceptibility-weighted MR imaging) used in this study, along with other more sensitive evaluative techniques. This type of intermodal comparison may improve the identification of concussions that were previously dependent on the unreliable self-reporting of recognized concussion symptomatology by the athlete or on poorly validated neuropsychological tests

A prospective study of physician-observed concussion during a varsity university ice hockey season: Incidence and neuropsychological changes. Part 2 of 4

Object: The primary objective of this study was to measure the incidence of concussion according to a relative number of athlete exposures among 25 male and 20 female varsity ice hockey players. The secondary objective was to present neuropsychological test results between preseason and postseason play and at 72 hours, 2 weeks, and 2 months after concussion. Methods: Every player underwent baseline assessments using the Sport Concussion Assessment Tool-2 (SCAT2), Immediate Post-Concussion Assessment and Cognitive Test (ImPACT), and MRI. Each regular season and postseason game was observed by 2 independent observers (a physician and a nonphysician observer). Players with a diagnosed concussion were removed from the game, examined in the team physician\u27s office using the SCAT2 and ImPACT, and sent to undergo MRI. Results: Eleven concussions occurred during the 55 physician-observed games (20%). The incidence of concussion, expressed as number of concussions per 1000 athlete exposures, was 10.70 for men and women combined in regular season play, 11.76 for men and women combined across both the regular season and playoff season, 7.50 for men and 14.93 for women in regular season play, and 8.47 for men across both the regular season and playoff season. One male player experienced repeat concussions. No concussions were reported during practice sessions, and 1 concussion was observed and diagnosed in an exhibition game. Neuropsychological testing suggested no statistically significant preseason/postseason differences between athletes who sustained a physician-diagnosed concussion and athletes who did not sustain a physician-diagnosed concussion on either the ImPACT or SCAT2. The athletes who sustained a physician-diagnosed concussion demonstrated few reliable changes postinjury. Conclusions: Although the incidence of game-related concussions per 1000 athlete exposures in this study was half the highest rate reported in the authors\u27 previous research, it was 3 times higher than the incidence reported by other authors within the literature concerning men\u27s collegiate ice hockey and 5 times higher than the highest rate previously reported for woman\u27s collegiate ice hockey. Interestingly, the present results suggest a substantively higher incidence of concussion among women (14.93) than men (7.50). The reproducible and significantly higher incidence of concussion among both men and woman ice hockey players, when compared with nonphysician-observed games, suggests a significant underestimation of sports concussion in the scientific literature

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe

Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies

Engineered SH2 domains with tailored specificities and enhanced affinities for phosphoproteome analysis

Protein phosphorylation is the most abundant post-translational modification in cells. Src homology 2 (SH2) domains specifically recognize phosphorylated tyrosine (pTyr) residues to mediate signaling cascades. A conserved pocket in the SH2 domain binds the pTyr side chain and the EF and BG loops determine binding specificity. By using large phage-displayed libraries, we engineered the EF and BG loops of the Fyn SH2 domain to alter specificity. Engineered SH2 variants exhibited distinct specificity profiles and were able to bind pTyr sites on the epidermal growth factor receptor, which were not recognized by the wild-type Fyn SH2 domain. Furthermore, mass spectrometry showed that SH2 variants with additional mutations in the pTyr-binding pocket that enhanced affinity were highly effective for enrichment of diverse pTyr peptides within the human proteome. These results showed that engineering of the EF and BG loops could be used to tailor SH2 domain specificity, and SH2 variants with diverse specificities and high affinities for pTyr residues enabled more comprehensive analysis of the human phosphoproteome. Statement: Src Homology 2 (SH2) domains are modular domains that recognize phosphorylated tyrosine embedded in proteins, transducing these post-translational modifications into cellular responses. Here we used phage display to engineer hundreds of SH2 domain variants with altered binding specificities and enhanced affinities, which enabled efficient and differential enrichment of the human phosphoproteome for analysis by mass spectrometry. These engineered SH2 domain variants will be useful tools for elucidating the molecular determinants governing SH2 domains binding specificity and for enhancing analysis and understanding of the human phosphoproteome

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI;furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown. Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI. Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian lnteruniversity Sports (CIS) ice hockey season 2011-2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes. Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008). Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI

Sex differences in white matter alterations following repetitive subconcussive head impacts in collegiate ice hockey players☆

Objective: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI. Methods: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Results: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores. Conclusions: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI; furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown.Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI.Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p &lt; 0.007) and correlated to ImPACT scores for both sexes.Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008).Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI

A prospective study of physician-observed concussion during a varsity university hockey season: metabolic changes in ice hockey players.

Object. Despite negative neuroimaging findings using traditional neuroimaging methods such as MRI and CT, sports-related concussions have been shown to cause neurometabolic changes in both the acute and subacute phases of head injury. However, no prospective clinical study has used an independent physician-observer design in the monitoring of these changes. The objective of this study was to evaluate the effects of repetitive concussive and subconcussive head impacts on neurometabolic concentrations in a prospective study of two Canadian Interuniversity Sports (CIS) ice hockey teams using MR spectroscopy (MRS). Methods. Forty-five ice hockey players (25 men and 20 women) participated in this study. All participants underwent pre- and postseason MRI, including spectroscopy imaging, using a 3-T MRI machine. The linear combination model was used to quantify the following ratios: glutamate/creatine-phosphocreatine (Cr), myoinositol/Cr, and N-acetylaspartate (NAA)/Cr. Individuals sustaining a medically diagnosed concussion were sent for MRI at 72 hours, 2 weeks, and 2 months after injury. Results. No statistically significant differences were observed between athletes who were diagnosed with a concussion and athletes who were not clinically diagnosed as sustaining a concussion. Although no statistically significant longitudinal metabolic changes were observed among athletes who were diagnosed with a concussion, the results demonstrated a predictable pattern of initial impairment, followed by a gradual return to ratios that were similar to, but lower than, baseline ratios. No significant pre- to postseason changes were demonstrated among men who were not observed to sustain a concussion. However, a substantively significant decrease in the NAA/Cr ratio was noted among the female hockey players (t(13) = 2.58, p = 0.02, h2 = 0.34). Conclusions. A key finding in this study, from the standpoint of future research design, is the demonstration of substantively significant metabolic changes among the players who were not diagnosed with a concussion. In addition, it may explain why there are few statistically significant differences demonstrated between players who were diagnosed with a concussion and players who were not diagnosed with a concussion (that is, the potency of the independent variable was diminished by the fact that the group of players not diagnosed with a concussion might be better described as a subgroup of the players who may have sustained a concussion but were not observed and diagnosed with a concussion). This result suggests that definitions of concussion may need to be revisited within sports with high levels of repetitive subconcussive head impacts. Future analysis of these data will examine the relationships between the modes of MRI (diffusion tensor imaging, MRS, and susceptibility-weighted MR imaging) used in this study, along with other more sensitive evaluative techniques. This type of intermodal comparison may improve the identification of concussions that were previously dependent on the unreliable self-reporting of recognized concussion symptomatology by the athlete or on poorly validated neuropsychological tests