80 research outputs found

    Spontaneous Iliopsoas Hematoma following Microvascular Free Tissue Transfer.

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    Spontaneous hematoma within the iliopsoas muscle (SIH) is a rare complication most commonly seen in coagulopathic patients. Often, patients undergoing microvascular free tissue transfer are anticoagulated for anastomotic patency. Here we describe two cases of postoperative SIH following contralateral anterolateral thigh (ALT) free tissue transfer for reconstruction of oncologic head and neck defects. Both patients described hip pain after mobilization and had a corresponding acute blood loss anemia. Diagnosis of SIH was confirmed by CT and both patients were managed conservatively. Given that anticoagulation is a common practice following head and neck free tissue transfer, surgeons should be aware of this potential complication

    Liquid‐Phase Synthesis of Highly Reactive Rare‐Earth Metal Nanoparticles

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    The first liquid-phase synthesis of high-quality, small-sized rare-earth metal nanoparticles (1–3 nm)—ranging from lanthanum as one of the largest (187 pm) to scandium as the smallest (161 pm) rare-earth metal—is shown. Size, oxidation state, and reactivity of the nanoparticles are examined (e.g., electron microscopy, electron spectroscopy, X-ray absorption spectroscopy, selected reactions). Whereas the nanoparticles are highly reactive (e.g. in contact to air and water), they are chemically stable as THF suspensions and powders under inert conditions. The reactivity can be controlled to obtain inorganic and metal–organic compounds at room temperature

    Spontaneous Iliopsoas Hematoma following Microvascular Free Tissue Transfer

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    Spontaneous hematoma within the iliopsoas muscle (SIH) is a rare complication most commonly seen in coagulopathic patients. Often, patients undergoing microvascular free tissue transfer are anticoagulated for anastomotic patency. Here we describe two cases of postoperative SIH following contralateral anterolateral thigh (ALT) free tissue transfer for reconstruction of oncologic head and neck defects. Both patients described hip pain after mobilization and had a corresponding acute blood loss anemia. Diagnosis of SIH was confirmed by CT and both patients were managed conservatively. Given that anticoagulation is a common practice following head and neck free tissue transfer, surgeons should be aware of this potential complication

    APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma

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    APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0–5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation

    Складова духовної культури та запорука стабільності політичного режиму Марокко

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    Головною тенденцією останніх десятиліть стали процеси глобалізації, які по-різному впливають на країни, так би мовити, „старого центру” та „периферії”. У „центрі” зосередились країни, в яких демократія має давні традиції, що зміцнювалися на засадах західноєвропейської християнської культури. Якщо взяти африканський континент, то побачимо там сукупність специфічних проблем, які одночасно наближають і віддаляють країни, що її складають, від глобалізаційних процесів. Отже, природно, що увага спеціалістів з проблем світового демократичного транзиту, культурології, політології, хоча й з різних причин, прикута до „чорного континенту”. Однією з проблем, що викликає небуденний інтерес дослідників, є стосунки, взаємодія західної та східної цивілізацій

    Routinely collected data for randomized trials: promises, barriers, and implications

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    This work was supported by Stiftung Institut für klinische Epidemiologie. The Meta-Research Innovation Center at Stanford University is funded by a grant from the Laura and John Arnold Foundation. The funders had no role in design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript or its submission for publication.Peer reviewedPublisher PD

    Involvement of the Glycogen Synthase Kinase-3 Signaling Pathway in TBI Pathology and Neurocognitive Outcome

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    BACKGROUND: Traumatic brain injury (TBI) sets in motion cascades of biochemical changes that result in delayed cell death and altered neuronal architecture. Studies have demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) effectively reduces apoptosis following a number of stimuli. The Wnt family of proteins, and growth factors are two major factors that regulate GSK-3 activity. In the absence of stimuli, GSK-3 is constitutively active and is complexed with Axin, adenomatous polyposis coli (APC), and casein kinase Iα (CK1α) and phosphorylates ß-Catenin leading to its degradation. Binding of Wnt to Frizzled receptors causes the translocation of GSK-3 to the plasma membrane, where it phosphorylates and inactivates the Frizzled co-receptor lipoprotein-related protein 6 (LRP6). Furthermore, the translocation of GSK-3 reduces ß-Catenin phosphorylation and degradation, leading to ß-Catenin accumulation and gene expression. Growth factors activate Akt, which in turn inhibits GSK-3 activity by direct phosphorylation, leading to a reduction in apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Using a rodent model, we found that TBI caused a rapid, but transient, increase in LRP6 phosphorylation that is followed by a modest decrease in ß-Catenin phosphorylation. Phospho-GSK-3β immunoreactivity was found to increase three days post injury, a time point at which increased Akt activity following TBI has been observed. Lithium influences several neurochemical cascades, including inhibiting GSK-3. When the efficacy of daily lithium was assessed, reduced hippocampal neuronal cell loss and learning and memory improvements were observed. These influences were partially mimicked by administration of the GSK-3-selective inhibitor SB-216763, as this drug resulted in improved motor function, but only a modest improvement in memory retention and no overt neuroprotection. CONCLUSION/SIGNIFICANCE: Taken together, our findings suggest that selective inhibition of GSK-3 may offer partial cognitive improvement. As a broad spectrum inhibitor of GSK-3, lithium offers neuroprotection and robust cognitive improvement, supporting its clinical testing as a treatment for TBI

    Antisera Against Certain Conserved Surface-Exposed Peptides of Nontypeable Haemophilus influenzae Are Protective

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    We thank Timothy VanWagoner for bioinformatics support, Huda Mussa for assistance with sequencing and Brett Cole for assistance with animal studies. We thank Arnold Smith for inspiration and persistence in understanding the basic biology of H. flu..The authors gratefully acknowledge the Children’s Hospital Foundation for promoting the Department of Pediatrics Research Infrastructure. The Foundation provided no financial support for this specific project.Nontypeable Haemophilus influenzae (NTHi) cause significant disease, including otitis media in children, exacerbations of chronic obstructive pulmonary disease, and invasive disease in susceptible populations. No vaccine is currently available to prevent NTHi disease. The interactions of NTHi and the human host are primarily mediated by lipooligosaccharide and a complex array of surface-exposed proteins (SEPs) that act as receptors, sensors and secretion systems. We hypothesized that certain SEPs are present in all NTHi strains and that a subset of these may be antibody accessible and represent protective epitopes. Initially we used 15 genomic sequences available in the GenBank database along with an additional 11 genomic sequences generated by ourselves to identify the core set of putative SEPs present in all strains. Using bioinformatics, 56 core SEPs were identified. Molecular modeling generated putative structures of the SEPs from which potential surface exposed regions were defined. Synthetic peptides corresponding to ten of these highly conserved surface-exposed regions were used to raise antisera in rats. These antisera were used to assess passive protection in the infant rat model of invasive NTHi infection. Five of the antisera were protective, thus demonstrating their in vivo antibody accessibility. These five peptide regions represent potential targets for peptide vaccine candidates to protect against NTHi infection.Yeshttp://www.plosone.org/static/editorial#pee
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