Regulation of Elovl and fatty acid metabolism

ABSTRACT Fatty acids are important regulators in the control of mammalian energy homeostasis. They are ingested in the diet but a significant amount are also endogenously produced by de novo lipogenesis. Fatty acid elongation beyond 16 carbons (palmitic acid) can occur to generate very long chain fatty acids (VLCFA), a process that is initiated by the rate-limiting condensation reaction. To date, six mammalian enzymes responsible for this reaction, ELOVL1-6 (Elongation of very long chain fatty acid), have been characterized. All of them exert substrate specificity and tissue-specific gene expression. In this thesis, factors that regulate fatty acid metabolism and, in particular, fatty acid synthesis and elongation will be presented. The enclosed papers discuss issues as to how Elovl3 is regulated in liver and in different adipose depots and what effects ablation of this enzyme causes to lipid homeostasis. In contrast to the expression of several other lipogenic genes, Elovl3 gene expression was not affected by fasting or refeeding. Instead, the gene expression was influenced by steroid hormones such as glucocorticoids and sex hormones. Also, hepatic Elovl3 gene expression followed a circadian rhythm, present exclusively in sexually mature male mice. Interestingly, despite reduced levels of leptin, Elovl3-ablated mice were shown to be resistant to diet induced weight gain, which seemed to be due to a decreased ratio between energy intake and energy expenditure. This phenotype was more pronounced in female mice. This thesis is based on the following papers, which are referred to in the text by their respective Roman numerals I-IV

A Review of Return to Play Issues and Sports-Related Concussion

Mild traumatic brain injury in sports has become a significant public health concern which has not only received the general public’s attention through multiple news media stories involving athletic concussions but has also resulted in local, state, and national legislative efforts to improve recogni-tion and management. The purpose of this article is to review the current literature for return to play (RTP) guidelines. State, regional, national, and professional legislation on sport-related concussion RTP management issues will be reviewed. This article will be helpful in developing a generalized systematic approach to concussion management and highlight specific RTP guidelines. The article will also touch upon specific contraindications to RTP, the role of neuropsychological testing in RTP, and other considerations and complications that affect an athlete’s ability to return to competition. Finally, considerations for terminating an athlete’s competitive season or ending a career after sus-taining a concussion resulting in prolonged and protracted symptomatology or repeated concussions will be reviewed. PubMed and Google were searched using the key terms mentioned below. In ad-dition, the author’s library of concussion-related articles was reviewed for the relevant literature

Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion

Recent research has suggested a possible link between sports-related concussions and neurodegen-erative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been sug-gested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 subconcussive and 57 concussive head impacts. The average subconcussive impact had a rotational acceleration of 1230 rad/s2 and a rotational ve-locity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion, and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention tech-niques

Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion

Recent research has suggested a possible link between sports-related concussions and neurodegen-erative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been sug-gested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 subconcussive and 57 concussive head impacts. The average subconcussive impact had a rotational acceleration of 1230 rad/s2 and a rotational ve-locity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion, and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention tech-niques

Test–retest, retest, and retest: Growth curve models of repeat testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)

Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test–retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test–retest reliability was demonstrated for all four composites as well

Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes

Objective: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes. Methods: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery. Results: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p \u3c 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics. Conclusion: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent

Can helmet design reduce the risk of concussion in football?

Of all sports, football accounts for the highest incidence of concussion in the US due to the large number of athletes participating and the nature of the sport. While there is general agreement that concussion incidence can be reduced through rule changes and teaching proper tackling technique, there remains debate as to whether helmet design may also reduce the incidence of concussion. A retrospective analysis was performed of head impact data collected from 1833 collegiate football players who were instrumented with helmet-mounted accelerometer arrays for games and practices. Data were collected between 2005 and 2010 from 8 collegiate football teams: Virginia Tech, University of North Carolina, University of Oklahoma, Dartmouth College, Brown University, University of Minnesota, Indiana University, and University of Illinois. Concussion rates were compared between players wearing Riddell VSR4 and Riddell Revolution helmets while controlling for the head impact exposure of each player. A total of 1,281,444 head impacts were recorded, from which 64 concussions were diagnosed. The relative risk of sustaining a concussion in a Revolution helmet compared with a VSR4 helmet was 46.1% (95% CI 28.1%–75.8%). When controlling for each player’s exposure to head impact, a significant difference was found between concussion rates for players in VSR4 and Revolution helmets (χ2 = 4.68, p = 0.0305). This study illustrates that differences in the ability to reduce concussion risk exist between helmet models in football. Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury

Analysis of head acceleration events in collegiate-level American football: A combination of qualitative video analysis and in-vivo head kinematic measurement

The contact nature of American football has made head acceleration exposure a concern. We aimed to quantify the head kinematics associated with direct helmet contact and inertial head loading events in collegiate-level American football. A cohort of collegiate-level players were equipped with instrumented mouthguards synchronised with time-stamped multiple camera-view video footage of matches and practice. Video-verified contact events were identified as direct helmet contact or inertial head loading events and categorised as blocking, blocked, tackling, tackled or ground contact. Linear mixed-effects models were utilised to compare peak head kinematics between contact event categories. The timestamp-based cross-verification of the video analysis and instrumented mouthguard approach resulted in 200 and 328 direct helmet contact and inertial head loading cases, respectively. Median linear acceleration, angular acceleration and angular velocity for inertial head loading cases was greater than direct helmet contact events by 8% (p = 0.007), 55% (p 0.05). The study highlights the potential of combining qualitative video analysis with in-vivo head kinematics measurements. The findings suggest that a number of direct helmet contact events sustained in American football are of lower magnitude to what is sustained during regular play (i.e. from inertial head loading). Additionally, the findings illustrate the importance of including all contact events, including direct helmet contact and inertial head loading cases, when assessing head acceleration exposure and player load during a season of American football

Timing of Concussion Diagnosis Is Related to Head Impact Exposure Prior to Injury

Concussions are commonly undiagnosed in an athletic environment because the post-injury signs and symptoms may be mild, masked by the subject, or unrecognized. This study compares measures of head impact frequency, location and kinematic response prior to cases of immediate and delayed concussion diagnosis

Head Impact Exposure Sustained by Football Players on Days of Diagnosed Concussion

This study compares the frequency and severity of head impacts sustained by football players on days with and without diagnosed concussion and to identify the sensitivity and specificity of single impact severity measures to diagnosed injury