Catastrophic Cervical Spine Injuries in Contact Sports.

Study Design Systematic review. Objectives To determine the incidence of catastrophic cervical spine injuries (CCSIs) among elite athletes participating in contact team sports and whether the incidence varies depending on the use of protective gear or by player position. Methods Electronic databases and reference lists of key articles published from January 1, 2000, to January 29, 2016, were searched. Results Fourteen studies were included that reported CCSI in rugby (n = 10), American football (n = 3), and Irish hurling (n = 1). Among Rugby Union players, incidence of CCSI was 4.1 per 100,000 player-hours. Among National Football League players, the CCSI rate was 0.6 per 100,000 player-exposures. At the collegiate level, the CCSI rate ranged from 1.1 to 4.7 per 100,000 player-years. Mixed populations of elite and recreational rugby players in four studies report a CCSI rate of 1.4 to 7.2 per 100,000 player-years. In this same population, the scrum accounted for 30 to 51% of total reported CCSIs in Rugby Union versus 0 to 4% in Rugby League. The tackle accounted for 29 to 39% of injuries in Rugby Union and 78 to 100% of injuries in Rugby League. Making a tackle was responsible for 29 to 80% of injuries in American football. Conclusion CCSIs are infrequent among elite athletes. There is insufficient evidence to determine the effect of protective gear (e.g., helmets, padding) on CCSI incidence. Scrum and tackle in rugby and tackling in American football account for the majority of CCSIs in each respective sport.This article is freely available via Open Access. Click on the Additional link above to access the full-text via the publisher's site.Published (Open Access

Change in function, pain, and quality of life following structured nonoperative treatment in patients with degenerative cervical myelopathy: a systematic review

Study Design: Systematic review. Objectives: The objective of this study was to conduct a systematic review to determine (1) change in function, pain, and quality of life following structured nonoperative treatment for degenerative cervical myelopathy (DCM); (2) variability of change in function, pain, and quality of life following different types of structured nonoperative treatment; (3) differences in outcomes observed between certain subgroups (eg, baseline severity score, duration of symptoms); and (4) negative outcomes and harms resulting from structured nonoperative treatment. Methods: A systematic search was conducted in Embase, PubMed, and the Cochrane Collaboration for articles published between January 1, 1950, and February 9, 2015. Studies were included if they evaluated outcomes following structured nonoperative treatment, including therapeutic exercise, manual therapy, cervical bracing, and/or traction. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and strength of the overall body of evidence was rated using guidelines outlined by the Grading of Recommendation Assessment, Development and Evaluation Working Group. Results: Of the 570 retrieved citations, 8 met inclusion criteria and were summarized in this review. Based on our results, there is very low evidence to suggest that structured nonoperative treatment for DCM results in either a positive or negative change in function as evaluated by the Japanese Orthopaedic Association score. Conclusion: There is a lack of evidence to determine the role of nonoperative treatment in patients with DCM. However, in the majority of studies, patients did not achieve clinically significant gains in function following structured nonoperative treatment. Furthermore, 23% to 54% of patients managed nonoperatively subsequently underwent surgical treatment

<i>Drosophila</i> PRL-1 Is a Growth Inhibitor That Counteracts the Function of the Src Oncogene

<div><p>Phosphatase of Regenerating Liver (PRL) family members have emerged as molecular markers that significantly correlate to the ability of many cancers to metastasize. However, contradictory cellular responses to PRL expression have been reported, including the inhibition of cell cycle progression. An obvious culprit for the discrepancy is the use of dozens of different cell lines, including many isolated from tumors or cultured cells selected for immortalization which may have missing or mutated modulators of PRL function. We created transgenic <i>Drosophila</i> to study the effects of PRL overexpression in a genetically controlled, organismal model. Our data support the paradigm that the normal cellular response to high levels of PRL is growth suppression and furthermore, that PRL can counter oncogenic activity of Src. The ability of PRL to inhibit growth under normal conditions is dependent on a CAAX motif that is required to localize PRL to the apical edge of the lateral membrane. However, PRL lacking the CAAX motif can still associate indiscriminately with the plasma membrane and retains its ability to inhibit Src function. We propose that PRL binds to other membrane-localized proteins that are effectors of Src or to Src itself. This first examination of PRL in a model organism demonstrates that PRL performs as a tumor suppressor and underscores the necessity of identifying the conditions that enable it to transform into an oncogene in cancer.</p></div

dPRL-1 counters Src-induced lethality and overgrowth.

<p>(A) Overexpression of Src in the dorsal compartment(s) of developing larva (<i>w; ap-Gal4; UAS-Src</i>) results in adult lethality, which is strongly rescued by co-expression of dPRL-1 or dPRL-1^NC. In contrast, overexpression of Ras in the dorsal compartment (<i>ap-GAL4, UAS-Ras</i>) resulted in lethality during pupal stages, which was accelerated by co-expression of dPRL-1. Data is presented as average +/− standard error of viable adults for animals overexpressing Src or viable prepupae for animals overexpressing Ras. Larval wings overexpressing Src are grossly overgrown (B) and have elevated levels of apoptosis (C); both phenotypes are suppressed by coexpression of dPRL-1. (D) Total Src protein (anti-Src) or activated Src (anti-phosphoSrc) are both elevated in animals overexpressing Src (top panels). Co-expression of dPRL-1 or dPRL-1^NC do not affect the levels, activation or localization of Src (middle, bottom panels).</p

Overexpression of dPRL-1 inhibits growth.

<p>Expression of dPRL-1 in the posterior compartment of the wing (<i>w; en-Gal4/UAS-dPRL-1; +</i>) reduces surface area by 20% (A) whereas expression in the dorsal compartment of the wing (<i>w; ap-Gal4, UAS-dPRL-1; +</i>) leads to an upward curvature (B). Expression in developing eyes (<i>ey-flp; UAS-dPRL-1; act>CD2>Gal4</i>) reduces the size of the adult head (C) while constitutive expression (<i>w; UAS-dPRL-1; act-Gal4</i>) prevents larvae from gaining mass (D). Lastly, expression of dPRL-1 in clones of cells in the developing wing disc (<i>hs-flp; UAS-dPRL-1; act>CD2>Gal4</i>) reduced proliferation (D).</p

Endogenous dPRL-1 levels and localization throughout <i>Drosophila</i> development.

<p>(A) Immunodetection of dPRL-1 (red) during embryo development. Directing dPRL-1 under the control of engrailed (<i>w; en-Gal4/UAS-dPRL-1</i>) demonstrates specificity of antibody (top, left corner) while subsequent images demonstrate that endogenous dPRL-1 is located in cytoplasmic compartments from 1 to 14 hours after egg laying. The bracket marks the location of first cellularization of the blastoderm, where individual cells first form and the arrow highlights the amnioserosa. (B) Higher magnification (600×) of dPRL-1 cytoplasmic localization during nascent cell formation. (C–G) dPRL-1 expression is cytoplasmic and membranous in various third instar larval tissues. (C) dPRL-1 in the midintestine throughout larval development (L1→L3) show the most variation in cytoplasmic staining (those with higher levels are indicated by asterisk). A selection of additional larval tissues— the wing disc (D–D'), eye/antenna disc (E–E', with morphogenetic furrow indicated by arrow), salivary gland (F–F') and proventriculus/gastric caecum (G–G') all shown. Blue staining marks nuclei and gray staining (D–G) is dPRL-1.</p

Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides

DNA vaccines or peptides are capable of inducing specific immunity; however, their translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein, we demonstrate that a novel immunization strategy, encompassing sequential exposure of the lymph node milieu to plasmid and peptide in a heterologous prime-boost fashion, results in considerable MHC class I-restricted immunity in mice. Plasmid-primed antigen expression was essential for the generation of a population of central memory T cells, expressing CD62L and low in PD-1, with substantial capability to expand and differentiate to peripheral memory and effector cells, following subsequent exposure to peptide. These vaccine-induced T cells dominated the T cell repertoire, were able to produce large amounts of chemokines and pro-inflammatory cytokines, and recognized tumor cells effectively. In addition to outlining a feasible and effective method to transform plasmid DNA vaccination into a potentially viable immunotherapeutic approach for cancer, this study sheds light on the mechanism of heterologous prime-boost and the considerable heterogeneity of MHC class I-restricted T cell responses

CAAX motif required for PRL-1 localization and function.

<p>Immunodetection of dPRL-1 (red) expressed in the dorsal compartment of the wing (<i>w; ap-GAL4, UAS-dPRL-1; +</i>) indicates that removal of the CAAX motif allows dPRL-1 to remain associated with the membrane (A, middle panels) but that it is no longer concentrated at the apical edge of epithelia (B, middle panel). (C) Co-staining with E-cadherin (green) indicates some overlap in dPRL-1 and E-cadherin localization. (D) Quantification of relative levels and position of dPRL-1 shows that co-expression of dPRL-1 and dPRL-1^NC resumes a restricted distribution although the ability of dPRL-1 to suppress growth is compromised (E).</p