932 research outputs found

    Accuracy of Pedicle Screw Placement Methods in Pediatrics and Adolescents Spinal Surgery: A Systematic Review and Meta-Analysis

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    STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Various methods of pedicle screw (PS) placement in spinal fusion surgery existed, which can be grouped into conventional freehand (FH), modified freehand (MF), and image-guided methods (including fluoroscopy-based navigation (FL), computed tomography-based navigation (CT-nav), robot-assisted (RA), and ultrasound-guided (UG)). However, the literature showed mixed findings regarding their accuracy and complications. This review aimed to discover which method of PS placement has the highest accuracy and lowest complication rate in pediatric and adolescent spinal fusion surgery. METHODS: A comprehensive search in MEDLINE (PubMed), EMBASE (OVID), CENTRAL, and Web of Science was conducted until May 2020 by 2 independent reviewers, followed by bias assessment with ROB 2 and ROBINS-I tools and quantification with meta-analysis. Overall evidence quality was determined with GRADE tool. RESULTS: Four RCTs and 2 quasi-RCTs/CCTs comprising 3,830 PS placed in 291 patients (4-22 years old) were analyzed. The lowest accuracy was found in FH (78.35%) while the highest accuracy was found in MF (95.86%). MF was more accurate than FH (OR 3.34 (95% CI, 2.33-4.79), P < .00 001, I2 = 0%). Three-dimensional printed drill template (as part of MF) was more accurate than FH (OR 3.10 (95% CI, 1.98-4.86), P < .00 001, I2 = 14%). Overall, complications occurred in 5.84% of the patients with 0.34% revision rate. Complication events in MF was lower compared to FH (OR 0.47 (95% CI, 0.10-2.15), P = .33, I2 = 0%). CONCLUSIONS: Meta-analysis shows that MF is more accurate than FH in pediatric and adolescent requiring PS placement for spinal fusion surgery

    Surgical management of mediastinal liposarcoma extending from hypopharynx to carina: Case report

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    We describe the complete resection of a giant, well-differentiated mediastinal liposarcoma extending retropharynx to envelop the aortic arch, trachea and esophagus following preoperative radiotherapy

    Form factors at strong coupling via a Y-system

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    We compute form factors in planar N=4 Super Yang-Mills at strong coupling. Namely we consider the overlap between an operator insertion and 2n gluons. Through the gauge/string duality these are given by minimal surfaces in AdS space. The surfaces end on an infinite periodic sequence of null segments at the boundary of AdS. We consider surfaces that can be embedded in AdS_3. We derive set of functional equations for the cross ratios as functions of the spectral parameter. These equations are of the form of a Y-system. The integral form of the Y-system has Thermodynamics Bethe Ansatz form. The area is given by the free energy of the TBA system or critical value of Yang-Yang functional. We consider a restricted set of operators which have small conformal dimension

    Phase transitions in the early and the present Universe

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    The evolution of the Universe is the ultimate laboratory to study fundamental physics across energy scales that span about 25 orders of magnitude: from the grand unification scale through particle and nuclear physics scales down to the scale of atomic physics. The standard models of cosmology and particle physics provide the basic understanding of the early and present Universe and predict a series of phase transitions that occurred in succession during the expansion and cooling history of the Universe. We survey these phase transitions, highlighting the equilibrium and non-equilibrium effects as well as their observational and cosmological consequences. We discuss the current theoretical and experimental programs to study phase transitions in QCD and nuclear matter in accelerators along with the new results on novel states of matter as well as on multi- fragmentation in nuclear matter. A critical assessment of similarities and differences between the conditions in the early universe and those in ultra- relativistic heavy ion collisions is presented. Cosmological observations and accelerator experiments are converging towards an unprecedented understanding of the early and present Universe.Comment: 41 pages, 16 figures, to appear in Ann. Rev. Nucl. Part. Sci 2006. Presentation improved, references adde

    Microtubules gate tau condensation to spatially regulate microtubule functions.

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    Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

    Spinning sugars in antigen biosynthesis: characterization of the Coxiella burnetii and Streptomyces griseus TDP-sugar epimerases (article)

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe dataset associated with this article is available in ORE at https://doi.org/10.24378/exe.3724The sugars streptose and dihydrohydroxystreptose (DHHS) are unique to the bacteria Streptomyces griseus and Coxiella burnetii, respectively. Streptose forms the central moiety of the antibiotic streptomycin, whilst DHHS is found in the O-antigen of the zoonotic pathogen C. burnetii. Biosynthesis of these sugars has been proposed to follow a similar path to that of TDP-rhamnose, catalyzed by the enzymes RmlA, RmlB, RmlC, and RmlD, but the exact mechanism is unclear. Streptose and DHHS biosynthesis unusually requires a ring contraction step that could be performed by orthologues of RmlC or RmlD. Genome sequencing of S. griseus and C. burnetii has identified StrM and CBU1838 proteins as RmlC orthologues in these respective species. Here, we demonstrate that both enzymes can perform the RmlC 3'',5'' double epimerization activity necessary to support TDP-rhamnose biosynthesis in vivo. This is consistent with the ring contraction step being performed on a double epimerized substrate. We further demonstrate that proton exchange is faster at the 3''-position than the 5''-position, in contrast to a previously studied orthologue. We additionally solved the crystal structures of CBU1838 and StrM in complex with TDP, and show that they form an active site highly similar to those of the previously characterized enzymes RmlC, EvaD, and ChmJ. These results support the hypothesis that streptose and DHHS are biosynthesized using the TDP pathway and that an RmlD paralogue most likely performs ring contraction following double epimerization. This work will support the elucidation of the full pathways for biosynthesis of these unique sugars.Biotechnology and Biological Sciences Research Council (BBSRC)DstlJohn Innes FoundationInnovate U

    Expression of phosphorylated raf kinase inhibitor protein (pRKIP) is a predictor of lung cancer survival

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    <p>Abstract</p> <p>Background</p> <p>Raf-1 kinase inhibitor protein (RKIP) has been reported to negatively regulate signal kinases of major survival pathways. RKIP activity is modulated in part by phosphorylation on Serine 153 by protein kinase C, which leads to dissociation of RKIP from Raf-1. RKIP expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. The prognostic power has typically been based on total RKIP expression and has not considered the significance of phospho-RKIP.</p> <p>Methods</p> <p>The present study examined the expression levels of both RKIP and phospho-RKIP in human lung cancer tissue microarray proteomics technology.</p> <p>Results</p> <p>Total RKIP and phospho-RKIP expression levels were similar in normal and cancerous tissues. phospho-RKIP levels slightly decreased in metastatic lesions. However, the expression levels of phospho-RKIP, in contrast to total RKIP, displayed significant predictive power for outcome with normal expression of phospho-RKIP predicting a more favorable survival compared to lower levels (P = 0.0118); this was even more pronounced in more senior individuals and in those with early stage lung cancer.</p> <p>Conclusions</p> <p>This study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival.</p

    Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma

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    Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure. Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples. This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance

    Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus

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    Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival. Escape from DCs was independent from DHN-melanin, as A. terreus conidia expressing wA showed no increased intracellular germination. Within DCs A. terreus conidia were protected from antifungals, whereas A. fumigatus conidia were efficiently cleared. Furthermore, while A. fumigatus conidia triggered expression of DC activation markers such as CD80, CD83, CD54, MHCII and CCR7, persistent A. terreus conidia were significantly less immunogenic. Moreover, DCs confronted with A. terreus conidia neither produced pro-inflammatory nor T-cell stimulating cytokines. However, TNF-α addition resulted in activation of DCs and provoked the expression of migration markers without inactivating intracellular A. terreus conidia. Therefore, persistence within DCs and possibly within other immune cells might contribute to the low response of A. terreus infections to antifungal treatment and could be responsible for its high dissemination rates

    Vaccinia-Related Kinase 1 Is Required for the Maintenance of Undifferentiated Spermatogonia in Mouse Male Germ Cells

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    Vaccinia-related kinase 1 (VRK1) is a crucial protein kinase for mitotic regulation. VRK1 is known to play a role in germ cell development, and its deficiency results in sterility. Here we describe that VRK1 is essential for the maintenance of spermatogonial stem cells. To determine whether VRK1 plays a role in these cells, we assessed the population size of undifferentiated spermatogonia. Flow cytometry analyses showed that the number of undifferentiated spermatogonia was markedly reduced in VRK1-deficient testes. VRK1 was highly expressed in spermatogonial populations, and approximately 66% of undifferentiated spermatogonia that were sorted as an Ep-CAM+/c-kit−/alpha-6-integrin+ population showed a positive signal for VRK1. Undifferentiated stem cells expressing Plzf and Oct4 but not c-kit also expressed VRK1, suggesting that VRK1 is an intrinsic factor for the maintenance of spermatogonial stem cells. Microarray analyses of the global testicular transcriptome and quantitative RT-PCR of VRK1-deficient testes revealed significantly reduced expression levels of undifferentiated spermatogonial marker genes in early postnatal mice. Together, these results suggest that VRK1 is required for the proliferation and differentiation of undifferentiated spermatogonia, which are essential for spermatogenic cell maintenance
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