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Munce T.A.,Sanford Sports Science Institute | Munce T.A.,Sanford Burnham Institute for Medical Research | Munce T.A.,University of South Dakota | Dorman J.C.,Sanford Sports Science Institute | And 8 more authors.
Medicine and Science in Sports and Exercise | Year: 2015

Football players are subjected to repetitive impacts that may lead to brain injury and neurologic dysfunction. Knowledge about head impact exposure (HIE) and consequent neurologic function among youth football players is limited. Purpose: This study aimed to measure and characterize HIE of youth football players throughout one season and explore associations between HIE and changes in selected clinical measures of neurologic function. Methods: Twenty-two youth football players (11-13 yr) wore helmets outfitted with a head impact telemetry (HIT) system to quantify head impact frequency, magnitude, duration, and location. Impact data were collected for each practice (27) and game (9) in a single season. Selected clinical measures of balance, oculomotor performance, reaction time, and self-reported symptoms were assessed before and after the season. Results: The median individual head impacts per practice, per game, and throughout the entire season were 9, 12, and 252, respectively. Approximately 50% of all head impacts (6183) had a linear acceleration between 10g and 20g, but nearly 2% were greater than 80g. Overall, the head impact frequency distributions in this study population were similar in magnitude and location as in high school and collegiate football, but total impact frequency was lower. Individual changes in neurologic function were not associated with cumulative HIE. Conclusion: This study provides a novel examination of HIE and associations with short-term neurologic function in youth football and notably contributes to the limited HIE data currently available for this population. Whereas youth football players can experience remarkably similar head impact forces as high school players, cumulative subconcussive HIE throughout one youth football season may not be detrimental to short-term clinical measures of neurologic function. Copyright © 2015 by the American College of Sports Medicine.

Greiman S.E.,University of North Dakota | Greiman S.E.,University of New Mexico | Rikihisa Y.,Ohio State University | Cain J.,Sanford Research | And 2 more authors.
Applied and Environmental Microbiology | Year: 2016

Neorickettsia spp. are bacterial endosymbionts of parasitic flukes (Digenea) that also have the potential to infect and cause disease (e.g., Sennetsu fever) in the vertebrate hosts of the fluke. One of the largest gaps in our knowledge of Neorickettsia biology is the very limited information available regarding the localization of the bacterial endosymbiont within its digenean host. In this study, we used indirect immunofluorescence microscopy to visualize Neorickettsia sp. within several life cycle stages of the digenean Plagiorchis elegans. Individual sporocysts, cercariae, metacercariae, and adults of P. elegans naturally infected with Neorickettsia sp. were obtained from our laboratory-maintained life cycle, embedded, sectioned, and prepared for indirect immunofluorescence microscopy using anti-Neorickettsia risticii horse serum as the primary antibody. Neorickettsia sp. was found within the tegument of sporocysts, throughout cercarial embryos (germ balls) and fully formed cercariae (within the sporocysts), throughout metacercariae, and within the tegument, parenchyma, vitellaria, uteri, testes, cirrus sacs, and eggs of adults. Interestingly, Neorickettsia sp. was not found within the ovarian tissue. This suggests that vertical transmission of Neorickettsia within adult digeneans occurs via the incorporation of infected vitelline cells into the egg rather than direct infection of the ooplasm of the oocyte, as has been described for other bacterial endosymbionts of invertebrates (e.g., Rickettsia and Wolbachia). © 2016, American Society for Microbiology. All Rights Reserved.

Munce T.A.,W Athletic | Munce T.A.,University of South Dakota | Munce T.A.,Sanford Burnham Institute for Medical Research | Dorman J.C.,W Athletic | And 9 more authors.
Journal of Child Neurology | Year: 2014

We assessed 10 youth football players (13.4 ± 0.7 y) immediately before and after their season to explore the effects of football participation on selected clinical measures of neurologic function. Postseason postural stability in a closed-eye condition was improved compared to preseason (P = .017). Neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery revealed that reaction time was significantly faster at postseason (P = .015). There were no significant preseason versus postseason differences in verbal memory (P = .507), visual memory (P = .750), or visual motor speed (P = .087). Oculomotor performance assessed by the King-Devick test was moderately to significantly improved (P = .047-.115). A 12-week season of youth football did not impair the postural stability, neurocognitive function, or oculomotor performance measures of the players evaluated. Though encouraging, continued and more comprehensive investigations of this at-risk population are warranted. © The Author(s) 2013.

De P.,Sanford Research | Miskimins K.,Cancer Biology Sanford Research | Dey N.,Sanford Research | Leyland-Jones B.,Sanford Research
Cancer Treatment Reviews | Year: 2013

The PI3K-AKT-mTOR network has been the major focus of attention for cancer researchers (both in the clinic and the laboratory) in the last decade. An incomplete knowledge of the molecular biology of this complex network has seen an expansion of first generation allosteric mTOR inhibitors, rapalogues, but also biomarker studies designed to identify the best responders of these agents. Currently, research in this pathway has focused on the dual nature of mTOR that is integrated by mTOR-RAPTOR complex (mTORC1) and mTOR-RICTOR complex (mTORC2). These two complexes are regulated by different upstream proteins and also regulated by multiple different compensatory feedback loops. The related advantage of feedback regulation of signaling systems is that it allows diversification in signal response. This deeper understanding has facilitated the development of a novel second generation of inhibitors that are able to affect both mTORC1 and mTORC2, and their downstream effectors, through inhibition of their catalytic activity (ATP competitive inhibitors, attacking the kinase domain of this protein) than binding to the FKBP12 regulatory proteins as for rapalogues. This article reviews the newest insight in the signaling network of the mTOR pathway, preclinical/clinical status of mTOR inhibitors (including second generation of kinase inhibitors) and then focuses on the development of a new wave of research related to combination therapies in subset specific breast tumors. © 2012 Elsevier Ltd.

Dey N.,Sanford Research | Dey N.,University of South Dakota | Barwick B.G.,Winship Cancer Institute | Moreno C.S.,Emory University | And 16 more authors.
BMC Cancer | Year: 2013

Background: Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies.Methods: We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease.Results: The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/β-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from β-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/β-catenin classifier had a greater risk of lung and brain, but not bone metastases.Conclusion: These data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways. © 2013 Dey et al.; licensee BioMed Central Ltd.

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