It Is a Mindboggling Dilemma: To Play or Not to Play Youth Sports Due to Concussion Risks?

Concussions and their long term effects resulting from football collisions have recently entered the forefront of social debate. Movies like Concussion as well as high-profile lawsuits due to post-concussion health effects have casted a spotlight on brain injuries at the collegiate and professional level. However, this debate has equal application in youth sports—recent studies show that sports-related concussions at the elementary, middle, and high school levels are equally concerning. Youth sports are safer when fewer athletes suffer from sports-related concussions. But litigation is not the best avenue to make youth sports safer. Youth sports can be improved by: 1) primary prevention efforts; 2) education and training; 3) continuous research; 4) development of better protective equipment; and 5) increased advocacy for greater safety across all youth sports. States should look at their own youth sports concussion laws to see where improvements can be made. This Article addresses whether parents and guardians should let their children play youth sports due to concussion risks. Part I discusses different perspectives on the pros, barriers, and cons of youth participating in sports, the participation rates in youth sports, and the impact that concussion lawsuits and movies like Concussion have had on those participation rates. Part II provides statistics on the rates of concussions in youth sports including variances based on gender and type of sport. Part III describes various concussion lawsuits filed within the previous seven years. Additionally, this Part highlights state laws on youth sports-related concussions. Part IV summarizes and provides a comprehensive analysis of the Pop Warner Settlement in March 2016, including the potential impact of the settlement on youth sports organizations. Finally, this Article concludes by proposing suggestions to youth athletes, parents, guardians, coaches, youth leagues, medical professionals, and legislatures to make youth sports safer and to help youth athletes successfully return to learn and to play should they sustain a sports-related concussion

Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2

Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia

Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites

Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

It Is a Mindboggling Dilemma: To Play or Not to Play Youth Sports Due to Concussion Risks?

Concussions and their long term effects resulting from football collisions have recently entered the forefront of social debate. Movies like Concussion as well as high-profile lawsuits due to post-concussion health effects have casted a spotlight on brain injuries at the collegiate and professional level. However, this debate has equal application in youth sports—recent studies show that sports-related concussions at the elementary, middle, and high school levels are equally concerning. Youth sports are safer when fewer athletes suffer from sports-related concussions. But litigation is not the best avenue to make youth sports safer. Youth sports can be improved by: 1) primary prevention efforts; 2) education and training; 3) continuous research; 4) development of better protective equipment; and 5) increased advocacy for greater safety across all youth sports. States should look at their own youth sports concussion laws to see where improvements can be made. This Article addresses whether parents and guardians should let their children play youth sports due to concussion risks. Part I discusses different perspectives on the pros, barriers, and cons of youth participating in sports, the participation rates in youth sports, and the impact that concussion lawsuits and movies like Concussion have had on those participation rates. Part II provides statistics on the rates of concussions in youth sports including variances based on gender and type of sport. Part III describes various concussion lawsuits filed within the previous seven years. Additionally, this Part highlights state laws on youth sports-related concussions. Part IV summarizes and provides a comprehensive analysis of the Pop Warner Settlement in March 2016, including the potential impact of the settlement on youth sports organizations. Finally, this Article concludes by proposing suggestions to youth athletes, parents, guardians, coaches, youth leagues, medical professionals, and legislatures to make youth sports safer and to help youth athletes successfully return to learn and to play should they sustain a sports-related concussion