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Find video protocols related to scientific articles indexed in Pubmed.
Care of the dying: how do we replace the Liverpool Care Pathway?
Br. Med. Bull.
PUBLISHED: 09-24-2014
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Death is an inescapable certainty of life. Variability in care for dying persons, however, is present. The Liverpool Care Pathway (LCP) sought to guide care for the last days of life but was phased out after intense scrutiny.
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Healing of a pyoderma gangrenosum at the site of a percutaneous endoscopically sited gastrostomy tube without tube removal.
BMJ Case Rep
PUBLISHED: 09-21-2014
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Pyoderma gangrenosum (PG) is a rare but important cause of pain and morbidity, and is associated with malignancy and shows pathergy. Occurrence at a percutaneous endoscopic gastrostomy (PEG) site is rare and may prompt PEG tube removal. This case describes management of PG at a PEG site in a man with squamous cell carcinoma of the orophayrnx. Successful healing of the lesion was achieved despite the PEG tube remaining in situ. Care was delivered within the hospice setting with support from the local dermatology service. Infection of the wound was treated with a recently licensed antimicrobial with a novel action. This allowed nutrition to continue, promoting healing further and ensuring a route of delivery for medications, avoiding intravenous therapy.
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Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway.
Evolution
PUBLISHED: 09-17-2014
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The mid-Cenozoic decline of atmospheric CO2 levels that promoted global climate change was critical to shaping contemporary arid ecosystems. Within angiosperms, two CO2 -concentrating mechanisms (CCMs)-CAM and C4 -evolved from the C3 photosynthetic pathway, enabling more efficient whole-plant function in such environments. Many angiosperm clades with CCMs are thought to have diversified rapidly due to Miocene aridification, but links between this climate change, CCM evolution, and increased net diversification rates (r) remain to be further understood. Euphorbia (?2000 species) includes a diversity of CAM-utilizing stem succulents, plus a single species-rich C4 subclade. We used ancestral state reconstructions with a dated molecular phylogeny to reveal that CCMs independently evolved 17-22 times in Euphorbia, principally from the Miocene onwards. Analyses assessing among-lineage variation in r identified eight Euphorbia subclades with significantly increased r, six of which have a close temporal relationship with a lineage-corresponding CCM origin. Our trait-dependent diversification analysis indicated that r of Euphorbia CCM lineages is approximately three-fold greater than C3 lineages. Overall, these results suggest that CCM evolution in Euphorbia was likely an adaptive strategy that enabled the occupation of increased arid niche space accompanying Miocene expansion of arid ecosystems. These opportunities evidently facilitated recent, replicated bursts of diversification in Euphorbia. This article is protected by copyright. All rights reserved.
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Characterization of Drug-Resistant Influenza A(H7N9) Variants Isolated From an Oseltamivir-Treated Patient in Taiwan.
J. Infect. Dis.
PUBLISHED: 08-14-2014
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?Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited.
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Coalescent versus Concatenation Methods and the Placement of Amborella as Sister to Water Lilies.
Syst. Biol.
PUBLISHED: 07-30-2014
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The molecular era has fundamentally reshaped our knowledge of the evolution and diversification of angiosperms. One outstanding question is the phylogenetic placement of Amborella trichopoda Baill., commonly thought to represent the first lineage of extant angiosperms. Here, we leverage publicly available data and provide a broad coalescent-based species tree estimation of 45 seed plants. By incorporating 310 nuclear genes, our coalescent analyses strongly support a clade containing Amborella plus water lilies (i.e., Nymphaeales) that is sister to all other angiosperms across different nucleotide rate partitions. Our results also show that commonly applied concatenation methods produce strongly supported, but incongruent placements of Amborella: slow-evolving nucleotide sites corroborate results from coalescent analyses, whereas fast-evolving sites place Amborella alone as the first lineage of extant angiosperms. We further explored the performance of coalescent versus concatenation methods using nucleotide sequences simulated on (i) the two alternate placements of Amborella with branch lengths and substitution model parameters estimated from each of the 310 nuclear genes and (ii) three hypothetical species trees that are topologically identical except with respect to the degree of deep coalescence and branch lengths. Our results collectively suggest that the Amborella alone placement inferred using concatenation methods is likely misled by fast-evolving sites. This appears to be exacerbated by the combination of long branches in stem group angiosperms, Amborella, and Nymphaeales with the short internal branch separating Amborella and Nymphaeales. In contrast, coalescent methods appear to be more robust to elevated substitution rates.
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Holoparasitic Rafflesiaceae possess the most reduced endophytes and yet give rise to the world's largest flowers.
Ann. Bot.
PUBLISHED: 06-18-2014
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Species in the holoparasitic plant family Rafflesiaceae exhibit one of the most highly modified vegetative bodies in flowering plants. Apart from the flower shoot and associated bracts, the parasite is a mycelium-like endophyte living inside their grapevine hosts. This study provides a comprehensive treatment of the endophytic vegetative body for all three genera of Rafflesiaceae (Rafflesia, Rhizanthes and Sapria), and reports on the cytology and development of the endophyte, including its structural connection to the host, shedding light on the poorly understood nature of this symbiosis.
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Long-term morphological stasis maintained by a plant-pollinator mutualism.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-04-2014
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Many major branches in the Tree of Life are marked by stereotyped body plans that have been maintained over long periods of time. One possible explanation for this stasis is that there are genetic or developmental constraints that restrict the origin of novel body plans. An alternative is that basic body plans are potentially quite labile, but are actively maintained by natural selection. We present evidence that the conserved floral morphology of a species-rich flowering plant clade, Malpighiaceae, has been actively maintained for tens of millions of years via stabilizing selection imposed by their specialist New World oil-bee pollinators. Nine clades that have lost their primary oil-bee pollinators show major evolutionary shifts in specific floral traits associated with oil-bee pollination, demonstrating that developmental constraint is not the primary cause of morphological stasis in Malpighiaceae. Interestingly, Malpighiaceae show a burst in species diversification coinciding with the origin of this plant-pollinator mutualism. One hypothesis to account for radiation despite morphological stasis is that although selection on pollinator efficiency explains the origin of this unique and conserved floral morphology, tight pollinator specificity subsequently permitted greatly enhanced diversification in this system.
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Substate federalism and fracking policies: does state regulatory authority trump local land use autonomy?
Environ. Sci. Technol.
PUBLISHED: 03-14-2014
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State officials responsible for the regulation of hydraulic fracturing (fracking) operations used in the production of oil and gas resources will inevitably confront a key policy issue; that is, to what extent can statewide regulations be developed without reducing land use autonomy typically exercised by local officials? Most state regulators have historically recognized the economic importance of industry jobs and favor the adoption of uniform regulatory requirements even if these rules preempt local policymaking authority. Conversely, many local officials seek to preserve land use autonomy to provide a greater measure of protection for public health and environmental quality goals. This paper examines how public officials in three states-Colorado, Pennsylvania, and Texas-address the question of state control versus local autonomy through their efforts to shape fracking policy decisions. While local officials within Texas have succeeded in developing fracking ordinances with relatively little interference from state regulators, Colorado and Pennsylvania have adopted a tougher policy stance favoring the retention of preemptive oil and gas statutes. Key factors that account for between state differences in fracking policy decisions include the strength of home rule provisions, gubernatorial involvement, and the degree of local experience with industrial economic activities.
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Leaf out times of temperate woody plants are related to phylogeny, deciduousness, growth habit and wood anatomy.
New Phytol.
PUBLISHED: 03-07-2014
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Leaf out phenology affects a wide variety of ecosystem processes and ecological interactions and will take on added significance as leaf out times increasingly shift in response to warming temperatures associated with climate change. There is, however, relatively little information available on the factors affecting species differences in leaf out phenology. An international team of researchers from eight Northern Hemisphere temperate botanical gardens recorded leaf out dates of c. 1600 woody species in 2011 and 2012. Leaf out dates in woody species differed by as much as 3 months at a single site and exhibited strong phylogenetic and anatomical relationships. On average, angiosperms leafed out earlier than gymnosperms, deciduous species earlier than evergreen species, shrubs earlier than trees, diffuse and semi-ring porous species earlier than ring porous species, and species with smaller diameter xylem vessels earlier than species with larger diameter vessels. The order of species leaf out was generally consistent between years and among sites. As species distribution and abundance shift due to climate change, interspecific differences in leaf out phenology may affect ecosystem processes such as carbon, water, and nutrient cycling. Our open access leaf out data provide a critical framework for monitoring and modelling such changes going forward.
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Single-entity hydrocodone extended-release capsules in opioid-tolerant subjects with moderate-to-severe chronic low back pain: a randomized double-blind, placebo-controlled study.
Pain Med
PUBLISHED: 02-12-2014
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A single-agent, extended-release formulation of hydrocodone (HC) has been developed for treatment of chronic moderate-to-severe pain. This study was designed to examine the safety and efficacy of HC extended release in opioid-experienced adults with moderate-to-severe chronic low back pain (CLBP).
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Floral structure and development in Rafflesiaceae with emphasis on their exceptional gynoecia.
Am. J. Bot.
PUBLISHED: 02-08-2014
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The holoparasitic plant family Rafflesiaceae include the world's largest flowers. Despite their iconic status, relatively little is known about the morphology and development of their flowers. A recent study clarified the organization of the outer (sterile) floral organs, surprisingly revealing that their distinctive floral chambers arose via different developmental pathways in the two major genera of the family. Here, we expand that research to investigate the structure and development of the reproductive organs of Rafflesiaceae.
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Plastid phylogenomics and green plant phylogeny: almost full circle but not quite there.
BMC Biol.
PUBLISHED: 01-31-2014
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A study in BMC Evolutionary Biology represents the most comprehensive effort to clarify the phylogeny of green plants using sequences from the plastid genome. This study highlights the strengths and limitations of plastome data for resolving the green plant phylogeny, and points toward an exciting future for plant phylogenetics, during which the vast and largely untapped territory of nuclear genomes will be explored.
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Pulse lavage is inadequate at removal of biofilm from the surface of total knee arthroplasty materials.
J Arthroplasty
PUBLISHED: 01-21-2014
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In acute periprosthetic infection, irrigation and debridement with component retention has a high failure rate in some studies. We hypothesize that pulse lavage irrigation is ineffective at removing biofilm from total knee arthroplasty (TKA) components. Staphylococcus aureus biofilm mass and location was directly visualized on arthroplasty materials with a photon collection camera and laser scanning confocal microscopy. There was a substantial reduction in biofilm signal intensity, but the reduction was less than a ten-fold decrease. This suggests that irrigation needs to be further improved for the removal of biofilm mass below the necessary bioburden level to prevent recurrence of acute infection in total knee arthroplasty.
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Attenuated total reflection fourier transform infrared (ATR-FTIR) spectral discrimination of brain tumour severity from serum samples.
J Biophotonics
PUBLISHED: 01-07-2014
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Gliomas are the most frequent primary brain tumours in adults with over 9,000 people diagnosed each year in the UK. A rapid, reagent-free and cost-effective diagnostic regime using serum spectroscopy would allow for rapid diagnostic results and for swift treatment planning and monitoring within the clinical environment. We report the use of ATR-FTIR spectral data combined with a RBF-SVM for the diagnosis of gliomas (high-grade and low-grade) from non-cancer with sensitivities and specificities on average of 93.75 and 96.53% respectively. The proposed diagnostic regime has the ability to reduce mortality and morbidity rates.
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Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009-2011.
Emerging Infect. Dis.
PUBLISHED: 11-27-2013
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We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009-2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.
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Developmental origins of the worlds largest flowers, Rafflesiaceae.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-28-2013
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Rafflesiaceae, which produce the worlds largest flowers, have captivated the attention of biologists for nearly two centuries. Despite their fame, however, the developmental nature of the floral organs in these giants has remained a mystery. Most members of the family have a large floral chamber defined by a diaphragm. The diaphragm encloses the reproductive organs where pollination by carrion flies occurs. In lieu of a functional genetic system to investigate floral development in these highly specialized holoparasites, we used comparative studies of structure, development, and gene-expression patterns to investigate the homology of their floral organs. Our results surprisingly demonstrate that the otherwise similar floral chambers in two Rafflesiaceae subclades, Rafflesia and Sapria, are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl. In contrast, in Sapria it is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl, which, although developed to varying degrees among the genera, appears to be a synapomorphy of the Rafflesiaceae. Thus, the characteristic features that define the floral chamber in these closely related genera are not homologous. These differences refute the prevailing hypothesis that similarities between Sapria and Rafflesia are ancestral in the family. Instead, our data indicate that Rafflesia-like and Sapria-like floral chambers represent two distinct derivations of this morphology. The developmental repatterning we identified in Rafflesia, in particular, may have provided architectural reinforcement, which permitted the explosive growth in floral diameter that has arisen secondarily within this subclade.
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Streptophyte Algae and the Origin of Land Plants Revisited Using Heterogeneous Models with Three New Algal Chloroplast Genomes.
Mol. Biol. Evol.
PUBLISHED: 10-17-2013
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The phylogenetic branching order of the green algal groups that gave rise to land plants remains uncertain despite its fundamental importance to understanding plant evolution. Previous studies have demonstrated that land plants evolved from streptophyte algae, but different lineages of streptophytes have been suggested to be the sister group of land plants. To better understand the evolutionary history of land plants and to determine the potential effects of "long-branch attraction" in phylogenetic reconstruction, we analyzed a chloroplast genome data set including three new chloroplast genomes from streptophyte algae: Coleochaetae orbicularis (Coleochaetales), Nitella hookeri (Charales), and Spirogyra communis (Zygnematales). We further applied a site pattern sorting method together with site- and time-heterogeneous models to investigate the branching order among streptophytes and land plants. Our chloroplast phylogenomic analyses support previous hypotheses based on nuclear data in placing Zygnematales alone, or a clade consisting of Coleochaetales plus Zygnematales, as the closest living relatives of land plants.
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New world bats harbor diverse influenza A viruses.
PLoS Pathog.
PUBLISHED: 10-01-2013
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Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.
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Targeting of the Purine Biosynthesis Host Cell Pathway Enhances the Activity of Tenofovir Against Sensitive and Drug-Resistant HIV-1.
J. Infect. Dis.
PUBLISHED: 08-06-2013
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Background.?Targeting host-cell pathways to increase the potency of nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) is an important strategy for clinical investigation. Resveratrol is a natural product that inhibits cellular ribonucleotide reductase, prolonging the S phase of the cell cycle and preferentially lowering dATP levels. Methods.?We performed in vitro evaluation of resveratrol on the antiviral activity of adenosine analog tenofovir (TFV) against sensitive and drug-resistant human immunodeficiency virus type 1 (HIV-1), from subtypes B and C, in primary cells. Results.?Resveratrol enhanced the antiviral activity of TFV by up to 10-fold and restored susceptibility of TFV-resistant viruses. Resveratrol prevented wild-type HIV-1 from developing phenotypic resistance to TFV. Notably, resveratrol enhanced TFV activity against sensitive and resistant HIV-1 from both subtypes B and C. Conclusions.?Prolonged wide-scale use of thymidine analogs in the setting of viral failure has limited the efficacy of second-line NRTI-based regimens in Africa. Moreover, the extensive use of ddI and d4T has led to high frequencies of the K65R mutation, further compromising TFV efficacy. In light of increasing resistance to commonly used NRTIs in global HIV treatment programs, targeting nucleoside biosynthesis with resveratrol, or derivatives with improved bioavailabilities, is a potential strategy to maintain, enhance, and restore susceptibility of commonly used NRTIs.
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Temperature-dependent shifts in phenology contribute to the success of exotic species with climate change.
Am. J. Bot.
PUBLISHED: 06-23-2013
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The study of how phenology may contribute to the assembly of plant communities has a long history in ecology. Climate change has brought renewed interest in this area, with many studies examining how phenology may contribute to the success of exotic species. In particular, there is increasing evidence that exotic species occupy unique phenological niches and track climate change more closely than native species.
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Compliance with Opioid Treatment Guidelines for Chronic Non-Cancer Pain (CNCP) in Primary Care at a Veterans Affairs Medical Center (VAMC).
Pain Med
PUBLISHED: 06-07-2013
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OBJECTIVE: The primary objective of this study was to measure prescribing compliance with the Veterans Affairs/Department of Defense treatment guidelines for chronic non-cancer pain (CNCP) in the primary care setting. We also determined the proportion of subjects who demonstrated aberrant drug-related behaviors (ADRBs) and the patient characteristics associated with them. DESIGN: This is a retrospective chart review. SETTING: Primary care setting in Veterans Affairs Medical Center. SUBJECTS: All patients with CNCP between the ages of 18 and 87 years who received opioid prescriptions for 3 or more consecutive months during a 1-year period (July 2009 to August 2010) were eligible for inclusion. A random sample of 800 patients was selected using pharmacy prescription database. Chi-square test was utilized to analyze associations between ADRB and patient characteristics. RESULTS: About half the patients in our sample had a signed opioid pain care agreement (OPCA), and at least one urine drug test (UDT) was obtained. UDT was positive for an illicit drug/unreported opioid in 19.5% of the patients, and negative for the prescribed drug in 25.2% of the sample. About 10% of the sample population had morphine equivalent dose equal to or greater than 200?mg/day. ADRBs were identified in 22.9% of the patients. Younger age, psychiatric comorbidities, history of substance abuse, and high opioid dose were associated with high risk of ADRB, but the presence of OPCA lowered the risk of ADRB. CONCLUSION: This article studied the prescribing practices of opioids in a primary care setting and can be used to enhance provider education regarding chronic pain guidelines.
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Enzyme-mediated methodology for the site-specific radiolabeling of antibodies based on catalyst-free click chemistry.
Bioconjug. Chem.
PUBLISHED: 05-30-2013
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An enzyme- and click chemistry-mediated methodology for the site-selective radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal (89)Zr, and the chelator desferrioxamine has been employed. The methodology consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the radiolabeling of the chelator-modified antibody with (89)Zr. The site-selective labeling methodology has proven facile, reproducible, and robust, producing (89)Zr-labeled radioimmunoconjguates that display high stability and immunoreactivity in vitro (>95%) in addition to highly selective tumor uptake (67.5 ± 5.0%ID/g) and tumor-to-background contrast in athymic nude mice bearing PSMA-expressing subcutaneous LNCaP xenografts. Ultimately, this strategy could play a critical role in the development of novel well-defined and highly immunoreactive radioimmunoconjugates for both the laboratory and clinic.
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Revision Total Hip and Knee Arthroplasty Implant Identification: Implications for Use of Unique Device Identification 2012 AAHKS Member Survey Results.
J Arthroplasty
PUBLISHED: 05-20-2013
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FDAs Unique Device Identification (UDI) Rule will mandate manufacturers to assign unique identifiers to their marketed devices. UDI use is expected to improve implant documentation and identification. A 2012 American Association of Hip and Knee Surgeons membership survey explored revision total hip and knee arthroplasty implant identification processes. 87% of surgeons reported regularly using at least 3 methods to identify failed implants pre-operatively. Median surgeon identification time was 20min; median staff time was 30min. 10% of implants could not be identified pre-operatively. 2% could not be identified intra-operatively. UDI in TJA registry and UDI in EMR were indicated practices to best support implant identification and save time. FDAs UDI rule sets the foundation for UDI use in patient care settings as standard practice for implant documentation.
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Evolution: pollen or pollinators - which came first?
Curr. Biol.
PUBLISHED: 04-27-2013
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A new study provides the first broad timeline of bee diversification. Several ancient bee clades are identified as ghost lineages that have left little fossil evidence of their existence. This timeline suggests that the rise of bees coincided with the largest flowering plant clade, the eudicots.
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Investigating the rapid diagnosis of gliomas from serum samples using infrared spectroscopy and cytokine and angiogenesis factors.
Anal Bioanal Chem
PUBLISHED: 04-22-2013
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The ability to diagnose brain cancer rapidly from serum samples is of great interest; such a diagnosis would allow for rapid testing and time to results providing a responsive diagnostic environment, ability to monitor treatment efficacy, early detection of recurrent tumours and screening techniques. Current methods rely upon subjective, time-consuming tests such as histological grading and are particularly invasive with the diagnostic test requiring hospitalisation of 2-3 days. A rapid diagnostic method based upon serum samples would allow for a relatively non-invasive test and open up the possibility of screening for brain cancer. We report for the first time the use of a Bioplex immunoassay to provide cytokine and angiogenesis factor levels that differ between serum from glioma and non-cancer patients specifically angiopoietin, follistatin, HGF, IL-8, leptin, PDGF-BB and PECAM-1 providing sensitivities and specificities as high as 88 % and 81 %, respectively. We also report, for the first time, the use of serum ATR-FTIR combined with a RBF SVM for the diagnosis of gliomas from non-cancer patients with sensitivities and specificities as high as 87.5 % and 100 %, respectively. We describe the combination of these techniques in an orthogonal diagnostic regime, providing strength to the diagnosis through data combinations, in a rapid diagnostic test within 5 h from serum collection (10 min for ATR-FTIR and 4 h for the Bioplex Immunoassay). This regime has the ability to revolutionise the clinical environment by providing objective measures for diagnosis allowing for increased efficiency with corresponding decreases in mortality, morbidity and economic impact upon the health services.
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Effect of ethnicity and insurance type on the outcome of open thoracic aortic aneurysm repair.
Ann Vasc Surg
PUBLISHED: 03-26-2013
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Mortality and complication rates for open thoracic aortic aneurysm repair have declined but remain high. The purpose of this study is to determine the influence of ethnicity and insurance type on procedure selection and outcome after open thoracic aneurysm repair.
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Advances in the floral structural characterization of the major subclades of Malpighiales, one of the largest orders of flowering plants.
Ann. Bot.
PUBLISHED: 03-13-2013
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Malpighiales are one of the largest angiosperm orders and have undergone radical systematic restructuring based on molecular phylogenetic studies. The clade has been recalcitrant to molecular phylogenetic reconstruction, but has become much more resolved at the suprafamilial level. It now contains so many newly identified clades that there is an urgent need for comparative studies to understand their structure, biology and evolution. This is especially true because the order contains a disproportionally large diversity of rain forest species and includes numerous agriculturally important plants. This study is a first broad systematic step in this endeavour. It focuses on a comparative structural overview of the flowers across all recently identified suprafamilial clades of Malpighiales, and points towards areas that desperately need attention.
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Quantitation of influenza virus using field flow fractionation and multi-angle light scattering for quantifying influenza A particles.
J. Virol. Methods
PUBLISHED: 02-27-2013
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Recent advances in instrumentation and data analysis in field flow fractionation and multi-angle light scattering (FFF-MALS) have enabled greater use of this technique to characterize and quantitate viruses. In this study, the FFF-MALS technique was applied to the characterization and quantitation of type A influenza virus particles to assess its usefulness for vaccine preparation. The use of FFF-MALS for quantitation and measurement of control particles provided data accurate to within 5% of known values, reproducible with a coefficient of variation of 1.9%. The methods, sensitivity and limit of detection were established by analyzing different volumes of purified virus, which produced a linear regression with fitting value R2 of 0.99. FFF-MALS was further applied to detect and quantitate influenza virus in the supernatant of infected MDCK cells and allantoic fluids of infected eggs. FFF fractograms of the virus present in these different fluids revealed similar distribution of monomeric and oligomeric virions. However, the monomer fraction of cell grown virus had greater size variety. Notably, ?-propialactone (BPL) inactivation of influenza viruses did not influence any of the FFF-MALS measurements. Quantitation analysis by FFF-MALS was compared to infectivity assays and real-time RT-PCR (qRT-PCR) and the limitations of each assay were discussed.
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Massive mitochondrial gene transfer in a parasitic flowering plant clade.
PLoS Genet.
PUBLISHED: 02-14-2013
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Recent studies have suggested that plant genomes have undergone potentially rampant horizontal gene transfer (HGT), especially in the mitochondrial genome. Parasitic plants have provided the strongest evidence of HGT, which appears to be facilitated by the intimate physical association between the parasites and their hosts. A recent phylogenomic study demonstrated that in the holoparasite Rafflesia cantleyi (Rafflesiaceae), whose close relatives possess the worlds largest flowers, about 2.1% of nuclear gene transcripts were likely acquired from its obligate host. Here, we used next-generation sequencing to obtain the 38 protein-coding and ribosomal RNA genes common to the mitochondrial genomes of angiosperms from R. cantleyi and five additional species, including two of its closest relatives and two host species. Strikingly, our phylogenetic analyses conservatively indicate that 24%-41% of these gene sequences show evidence of HGT in Rafflesiaceae, depending on the species. Most of these transgenic sequences possess intact reading frames and are actively transcribed, indicating that they are potentially functional. Additionally, some of these transgenes maintain synteny with their donor and recipient lineages, suggesting that native genes have likely been displaced via homologous recombination. Our study is the first to comprehensively assess the magnitude of HGT in plants involving a genome (i.e., mitochondria) and a species interaction (i.e., parasitism) where it has been hypothesized to be potentially rampant. Our results establish for the first time that, although the magnitude of HGT involving nuclear genes is appreciable in these parasitic plants, HGT involving mitochondrial genes is substantially higher. This may represent a more general pattern for other parasitic plant clades and perhaps more broadly for angiosperms.
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Record-breaking early flowering in the eastern United States.
PLoS ONE
PUBLISHED: 01-16-2013
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Flowering times are well-documented indicators of the ecological effects of climate change and are linked to numerous ecosystem processes and trophic interactions. Dozens of studies have shown that flowering times for many spring-flowering plants have become earlier as a result of recent climate change, but it is uncertain if flowering times will continue to advance as temperatures rise. Here, we used long-term flowering records initiated by Henry David Thoreau in 1852 and Aldo Leopold in 1935 to investigate this question. Our analyses demonstrate that record-breaking spring temperatures in 2010 and 2012 in Massachusetts, USA, and 2012 in Wisconsin, USA, resulted in the earliest flowering times in recorded history for dozens of spring-flowering plants of the eastern United States. These dramatic advances in spring flowering were successfully predicted by historical relationships between flowering and spring temperature spanning up to 161 years of ecological change. These results demonstrate that numerous temperate plant species have yet to show obvious signs of physiological constraints on phenological advancement in the face of climate change.
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Deep Genetic Divergence between Disjunct Refugia in the Arctic-Alpine Kings Crown, Rhodiola integrifolia (Crassulaceae).
PLoS ONE
PUBLISHED: 01-01-2013
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Despite the strength of climatic variability at high latitudes and upper elevations, we still do not fully understand how plants in North America that are distributed between Arctic and alpine areas responded to the environmental changes of the Quaternary. To address this question, we set out to resolve the evolutionary history of the Kings Crown, Rhodiola integrifolia using multi-locus population genetic and phylogenetic analyses in combination with ecological niche modeling. Our population genetic analyses of multiple anonymous nuclear loci revealed two major clades within R. integrifolia that diverged from each other ~ 700 kya: one occurring in Beringia to the north (including members of subspecies leedyi and part of subspecies integrifolia), and the other restricted to the Southern Rocky Mountain refugium in the south (including individuals of subspecies neomexicana and part of subspecies integrifolia). Ecological niche models corroborate our hypothesized locations of refugial areas inferred from our phylogeographic analyses and revealed some environmental differences between the regions inhabited by its two subclades. Our study underscores the role of geographic isolation in promoting genetic divergence and the evolution of endemic subspecies in R. integrifolia. Furthermore, our phylogenetic analyses of the plastid spacer region trnL-F demonstrate that among the native North American species, R. integrifolia and R. rhodantha are more closely related to one another than either is to R. rosea. An understanding of these historic processes lies at the heart of making informed management decisions regarding this and other Arctic-alpine species of concern in this increasingly threatened biome.
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Phylogenomics and coalescent analyses resolve extant seed plant relationships.
PLoS ONE
PUBLISHED: 01-01-2013
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The extant seed plants include more than 260,000 species that belong to five main lineages: angiosperms, conifers, cycads, Ginkgo, and gnetophytes. Despite tremendous effort using molecular data, phylogenetic relationships among these five lineages remain uncertain. Here, we provide the first broad coalescent-based species tree estimation of seed plants using genome-scale nuclear and plastid data By incorporating 305 nuclear genes and 47 plastid genes from 14 species, we identify that i) extant gymnosperms (i.e., conifers, cycads, Ginkgo, and gnetophytes) are monophyletic, ii) gnetophytes exhibit discordant placements within conifers between their nuclear and plastid genomes, and iii) cycads plus Ginkgo form a clade that is sister to all remaining extant gymnosperms. We additionally observe that the placement of Ginkgo inferred from coalescent analyses is congruent across different nucleotide rate partitions. In contrast, the standard concatenation method produces strongly supported, but incongruent placements of Ginkgo between slow- and fast-evolving sites. Specifically, fast-evolving sites yield relationships in conflict with coalescent analyses. We hypothesize that this incongruence may be related to the way in which concatenation methods treat sites with elevated nucleotide substitution rates. More empirical and simulation investigations are needed to understand this potential weakness of concatenation methods.
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Structural and Antigenic Variation among Diverse Clade 2 H5N1 Viruses.
PLoS ONE
PUBLISHED: 01-01-2013
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Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-binding properties of three H5N1 HPAI virus hemagglutinins, which were recently selected by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1), A/Hubei/1/2010 (Hubei10, clade 2.3.2.1) and A/Anhui/1/2005 (Anhui05, clade 2.3.4)]. These analyses revealed that antigenic diversity among these three isolates was restricted to changes in the size and charge of amino acid side chains at a handful of positions, spatially equivalent to the antigenic sites identified in H1 subtype viruses circulating among humans. All three of the H5N1 viruses analyzed in this study were responsible for fatal human infections, with the most recently-isolated strains, Hubei10 and Egypt10, containing multiple residues in the receptor-binding site of the HA, which were suspected to enhance mammalian transmission. However, glycan-binding analyses demonstrated a lack of binding to human ?2-6-linked sialic acid receptor analogs for all three HAs, reinforcing the notion that receptor-binding specificity contributes only partially to transmissibility and pathogenesis of HPAI viruses and suggesting that changes in host specificity must be interpreted in the context of the host and environmental factors, as well as the virus as a whole. Together, our data reveal structural linkages with phylogenetic and antigenic analyses of recently emerged H5N1 virus clades and should assist in interpreting the significance of future changes in antigenic and receptor-binding properties.
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Divergent genetic mechanisms underlie reversals to radial floral symmetry from diverse zygomorphic flowered ancestors.
Front Plant Sci
PUBLISHED: 01-01-2013
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Malpighiaceae possess flowers with a unique bilateral symmetry (zygomorphy), which is a hypothesized adaptation associated with specialization on neotropical oil bee pollinators. Gene expression of two representatives of the CYC2 lineage of floral symmetry TCP genes, CYC2A and CYC2B, demarcate the adaxial (dorsal) region of the flower in the characteristic zygomorphic flowers of most Malpighiaceae. Several clades within the family, however, have independently lost their specialized oil bee pollinators and reverted to radial flowers (actinomorphy) like their ancestors. Here, we investigate CYC2 expression associated with four independent reversals to actinomorphy. We demonstrate that these reversals are always associated with alteration of the highly conserved CYC2 expression pattern observed in most New World (NW) Malpighiaceae. In NW Lasiocarpus and Old World (OW) Microsteria, the expression of CYC2-like genes has expanded to include the ventral region of the corolla. Thus, the pattern of gene expression in these species has become radialized, which is comparable to what has been reported in the radial flowered legume clade Cadia. In striking contrast, in NW Psychopterys and OW Sphedamnocarpus, CYC2-like expression is entirely absent or at barely detectable levels. This is more similar to the pattern of CYC2 expression observed in radial flowered Arabidopsis. These results collectively indicate that, regardless of geographic distribution, reversals to similar floral phenotypes in this large tropical angiosperm clade have evolved via different genetic changes from an otherwise highly conserved developmental program.
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Plant evolution: pulses of extinction and speciation in gymnosperm diversity.
Curr. Biol.
PUBLISHED: 12-24-2011
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Living gymnosperms represent the survivors of ancient seed plant lineages whose fossil record reaches back 270 million years. Two recent studies find that recent pulses of extinction and speciation have shaped todays gymnosperm diversity, contradicting the widespread assumption that gymnosperms have remained largely unchanged for tens of millions of years.
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Study of effectiveness of mifepristone for glioma cell line growth suppression.
Br J Neurosurg
PUBLISHED: 11-21-2011
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Glioblastoma multiforme is a malignant primary brain tumour with very limited treatment options. Any addition to existing treatment options which can improve prognosis and life expectancy is useful. In our study, we look at the usefulness of anti-progestogen mifepristone in causing growth suppression of glioma cell lines in the laboratory.
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In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity.
Virology
PUBLISHED: 08-27-2011
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Acquisition of ?2-6 sialoside receptor specificity by ?2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding ?2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased ?2-6 and minimally decreased ?2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly ?2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans.
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Emergency department visits: we are not prepared.
Am J Emerg Med
PUBLISHED: 08-16-2011
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Emergency department (ED) staff comments frequently about how patients are poorly prepared to answer important medical questions. To determine if the impression that patients were or were not prepared, a total of 309 patients were all asked a series of important medical questions and were graded as positive (or prepared) if they answered the question completely or negative (unprepared) if they partially answered, did not answer, or changed their answer during the ED stay. The patient population was older (mean age, 60 years) and was seen at 1 specialty hospital. Results indicated that many people were not prepared with information about their allergies, medications, medical and surgical histories, and some, even their physicians names. Patients were least prepared to know about an advance directive (79%) or to know their complete medical history (70%). Results indicated that most patients (99%) were not prepared to answer at least 1 or more important medical questions. The discussion considers why patients and others are not prepared for an ED visit and provides examples of ways to help people better prepare for such a visit.
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The virulence of 1997 H5N1 influenza viruses in the mouse model is increased by correcting a defect in their NS1 proteins.
J. Virol.
PUBLISHED: 05-18-2011
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The NS1 protein of human influenza A viruses binds the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a protein required for 3 end processing of cellular pre-mRNAs, thereby inhibiting production of beta interferon (IFN-?) mRNA. The NS1 proteins of pathogenic 1997 H5N1 viruses contain the CPSF30-binding site but lack the consensus amino acids at positions 103 and 106, F and M, respectively, that are required for the stabilization of CPSF30 binding, resulting in nonoptimal CPSF30 binding in infected cells. Here we have demonstrated that strengthening CPSF30 binding, by changing positions 103 and 106 in the 1997 H5N1 NS1 protein to the consensus amino acids, results in a remarkable 300-fold increase in the lethality of the virus in mice. Unexpectedly, this increase in virulence is not associated with increased lung pathology but rather is characterized by faster systemic spread of the virus, particularly to the brain, where increased replication and severe pathology occur. This increased spread is associated with increased cytokine and chemokine levels in extrapulmonary tissues. We conclude that strengthening CPSF30 binding by the NS1 protein of 1997 H5N1 viruses enhances virulence in mice by increasing the systemic spread of the virus from the lungs, particularly to the brain.
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Angiosperm phylogeny: 17 genes, 640 taxa.
Am. J. Bot.
PUBLISHED: 04-08-2011
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Recent analyses employing up to five genes have provided numerous insights into angiosperm phylogeny, but many relationships have remained unresolved or poorly supported. In the hope of improving our understanding of angiosperm phylogeny, we expanded sampling of taxa and genes beyond previous analyses.
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A hetero-dimer model for concerted action of vitamin K carboxylase and vitamin K reductase in vitamin K cycle.
J. Theor. Biol.
PUBLISHED: 03-23-2011
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Vitamin K carboxylase (VKC) is believed to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form which then reacts with CO(2) and glutamate to generate ?-carboxyglutamic acid (Gla). Subsequently, vitamin K epoxide reductase (VKOR) is thought to convert the alkoxide-epoxide to a hydroquinone form. By recycling vitamin K, the two integral-membrane proteins, VKC and VKOR, maintain vitamin K levels and sustain the blood coagulation cascade. Unfortunately, NMR or X-ray crystal structures of the two proteins have not been characterized. Thus, our understanding of the vitamin K cycle is only partial at the molecular level. In this study, based on prior biochemical experiments on VKC and VKOR, we propose a hetero-dimeric form of VKC and VKOR that may explain the efficient oxidation and reduction of vitamin K during the vitamin K cycle.
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Phylogeny of the clusioid clade (Malpighiales): evidence from the plastid and mitochondrial genomes.
Am. J. Bot.
PUBLISHED: 01-26-2011
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The clusioid clade includes five families (i.e., Bonnetiaceae, Calophyllaceae, Clusiaceae s.s., Hypericaceae, and Podostemaceae) represented by 94 genera and ?1900 species. Species in this clade form a conspicuous element of tropical forests worldwide and are important in horticulture, timber production, and pharmacology. We conducted a taxon-rich multigene phylogenetic analysis of the clusioids to clarify phylogenetic relationships in this clade.
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Hemangioma causing deformational plagiocephaly.
J Craniofac Surg
PUBLISHED: 01-15-2011
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Hemangioma is the most common tumor of infancy, occurring mostly in the head and neck region. Intervention during the proliferating phase is indicated if the lesion poses a threat to life or function. Posterior head and neck hemangioma causing deformational plagiocephaly is a further indication for intervention.
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The development of vaccine viruses against pandemic A(H1N1) influenza.
Vaccine
PUBLISHED: 01-01-2011
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Wild type human influenza viruses do not usually grow well in embryonated hens eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses. Two approaches were followed, the classical reassortment approach and the more recent reverse genetics approach. This report describes the development and the characteristics of current pandemic H1N1 candidate vaccine viruses.
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A complete generic phylogeny of Malpighiaceae inferred from nucleotide sequence data and morphology.
Am. J. Bot.
PUBLISHED: 11-24-2010
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• Premise of the study: The Malpighiaceae include ?1300 tropical flowering plant species in which generic definitions and intergeneric relationships have long been problematic. The goals of our study were to resolve relationships among the 11 generic segregates from the New World genus Mascagnia, test the monophyly of the largest remaining Malpighiaceae genera, and clarify the placement of Old World Malpighiaceae. • Methods: We combined DNA sequence data for four genes (plastid ndhF, matK, and rbcL and nuclear PHYC) from 338 ingroup accessions that represented all 77 currently recognized genera with morphological data from 144 ingroup species to produce a complete generic phylogeny of the family. • Key results and conclusions: The genera are distributed among 14 mostly well-supported clades. The interrelationships of these major subclades have strong support, except for the clade comprising the wing-fruited genera (i.e., the malpighioid+Amorimia, Ectopopterys, hiraeoid, stigmaphylloid, and tetrapteroid clades). These results resolve numerous systematic problems, while others have emerged and constitute opportunities for future study. Malpighiaceae migrated from the New to Old World nine times, with two of those migrants being very recent arrivals from the New World. The seven other Old World clades dispersed much earlier, likely during the Tertiary. Comparison of floral morphology in Old World Malpighiaceae with their closest New World relatives suggests that morphological stasis in the New World likely results from selection by neotropical oil-bee pollinators and that the morphological diversity found in Old World flowers has evolved following their release from selection by those bees.
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Outcomes of kidney transplantation in HIV-infected recipients.
N. Engl. J. Med.
PUBLISHED: 11-19-2010
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The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.
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Gene delivery of AAV2-neurturin for Parkinsons disease: a double-blind, randomised, controlled trial.
Lancet Neurol
PUBLISHED: 10-20-2010
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In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function in patients with advanced Parkinsons disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial.
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The importance of phylogeny to the study of phenological response to global climate change.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 09-08-2010
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Climate change has resulted in major changes in the phenology--i.e. the timing of seasonal activities, such as flowering and bird migration--of some species but not others. These differential responses have been shown to result in ecological mismatches that can have negative fitness consequences. However, the ways in which climate change has shaped changes in biodiversity within and across communities are not well understood. Here, we build on our previous results that established a link between plant species phenological response to climate change and a phylogenetic bias in species decline in the eastern United States. We extend a similar approach to plant and bird communities in the United States and the UK that further demonstrates that climate change has differentially impacted species based on their phylogenetic relatedness and shared phenological responses. In plants, phenological responses to climate change are often shared among closely related species (i.e. clades), even between geographically disjunct communities. And in some cases, this has resulted in a phylogenetically biased pattern of non-native species success. In birds, the pattern of decline is phylogenetically biased but is not solely explained by phenological response, which suggests that other traits may better explain this pattern. These results illustrate the ways in which phylogenetic thinking can aid in making generalizations of practical importance and enhance efforts to predict species responses to future climate change.
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Impact of the economic downturn on adult reconstruction surgery: a survey of the American Association of Hip and Knee Surgeons.
J Arthroplasty
PUBLISHED: 08-13-2010
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To evaluate the effects of the economic downturn on adult reconstruction surgery in the United States, a survey of the American Association of Hip and Knee Surgeons (AAHKS) membership was conducted. The survey evaluated surgical and patient volume, practice type, hospital relationship, total joint arthroplasty cost control, employee staffing, potential impact of Medicare reimbursement decreases, attitudes toward health care reform options and retirement planning. A surgical volume decrease was reported by 30.4%. An outpatient visit decrease was reported by 29.3%. A mean loss of 29.9% of retirement savings was reported. The planned retirement age increased to 65.3 years from 64.05 years. If Medicare surgeon reimbursement were to decrease up to 20%, 49% to 57% of AAHKS surgeons would be unable to provide care for Medicare patients, resulting in an unmet need of 92,650 to 160,818 total joint arthroplasty procedures among AAHKS surgeons alone. Decreases in funding for surgeons and inadequate support for subspecialty training will likely impact access and quality for Americans seeking adult reconstruction surgery.
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Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity.
Toxicol Pathol
PUBLISHED: 07-08-2010
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Several multikinase angiogenesis inhibitors demonstrate mitochondrial and/or cardiovascular toxicity, suggesting an on-target pharmacologic effect. To evaluate whether cardiotoxicity is directly related to vascular endothelial growth factor receptor inhibition, we investigated the effects of sunitinib, sorafenib, and pazopanib on myocardial function and structure. We used a rat model to assess myocardial effects of the inhibitors concurrently exposed to the cardiac stressor dobutamine. Echocardiographic abnormalities including premature ventricular contractions, decreases in heart rate, circumferential strain, and radial and circumferential strain rates were noted with sorafenib, but not with sunitinib or pazopanib. Ultrastructural analysis of ventricular cardiomyocytes by transmission electron microscopy revealed mitochondrial swelling, dense deposits, and matrix cavitation in rats given sunitinib and disrupted mitochondrial cristae in rats given sorafenib, but there were no effects with pazopanib. Effects on neonatal rat cardiomyocyte cultures were assessed, which identified decreases in mitochondrial membrane potential with sunitinib treatment, but not with sorafenib or pazopanib. Intracellular adenosine triphosphate depletion was observed with sunitinib and sorafenib, but not pazopanib. Our results show that cardiotoxicity is not necessarily related to a pharmacologic classwide effect of vascular endothelial growth factor receptor inhibition, and the rat myocardial structural and functional changes identified in this study may be instead a result of inhibition of other kinase pathways, the mechanism of which may be associated with mitochondrial toxicity.
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A molecular dynamics study of the early stages of amyloid-beta(1-42) oligomerization: the role of lipid membranes.
Proteins
PUBLISHED: 07-06-2010
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As research progresses toward understanding the role of the amyloid-beta (Abeta) peptide in Alzheimers disease, certain aspects of the aggregation process for Abeta are still not clear. In particular, the accepted constitution of toxic aggregates in neurons has shifted toward small oligomers. However, the process of forming these oligomers in cells is also not full clear. Even more interestingly, it has been implied that cell membranes, and, in particular, anionic lipids within those membranes, play a key role in the progression of Abeta aggregation, but the exact nature of the Abeta-membrane interaction in this process is unknown. In this work, we use a thermodynamic cycle and umbrella sampling molecular dynamics to investigate dimerization of the 42-residue Abeta peptide on model zwitterionic dipalmitoylphosphatidylcholine (DPPC) or model anionic dioleoylphosphatidylserine (DOPS) bilayer surfaces. We determined that Abeta dimerization was strongly favored through interactions with the DOPS bilayer. Further, our calculations showed that the DOPS bilayer promoted strong protein-protein interactions within the Abeta dimer, whereas DPPC favored strong protein-lipid interactions. By promoting dimer formation and subsequent dimer release into the solvent, the DOPS bilayer acts as a catalyst in Abeta aggregation.
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[Protomedicato and pharmacy in Castile at the end of the sixteenth century: "Catálogo de las Cosas que los Boticarios han de tener en sus Boticas" (Catalogue of the things that apothecaries must have in their shops), by Andrés Zamudio de Alfaro, Protomédi
Asclepio
PUBLISHED: 07-02-2010
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In this article we present a catalogue of medicinal products preserved in a manuscript copy among the papers of a druggist who died in Madrid in 1599. This catalogue, whose title expresses its normative character, contains 423 entries and is signed by Andrés Zamudio de Alfaro, Protomédico General of Castile from 1592 until his death in 1599. It was presumably issued by the Real Tribunal del Protomedicato during the last decade of the sixteenth century for the use of the protomédicos and examiners who carried out official visits to apothecaries under the aegis of the Tribunal, in accordance with the royal decrees of 1588 and 1593, and was also distributed among the apothecaries themselves and their suppliers, such as the druggist who possessed the copy edited here. The document offers valuable evidence of the policy of normalization of medical, and specifically pharmaceutical, practice imposed during this period by the State through the Protomedicato.
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Quantum Chemical Study of the Mechanism of Action of Vitamin K Carboxylase in Solvent.
Int J Quantum Chem
PUBLISHED: 06-25-2010
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We investigate the post-translational generation of Gla (?-carboxy glutamic acid) from Glu (glutamic acid) by vitamin K carboxylase (VKC) in solvent. VKC is thought to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form, which then reacts with CO(2) to generate an essential ingredient in blood coagulation, ?-carboxyglutamic acid (Gla). The generation of Gla from Glu is found to be exergenic (-15 kcal/mol) in aqueous solution with the SM6 method. We also produced the free energy profile for this model biochemical process with other solvent methods (polarizable continuum model, dielectric polarizable continuum model) and different dielectric constants. The biological implications are discussed.
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Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.
Cephalalgia
PUBLISHED: 06-15-2010
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Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism.
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Spring expansion is influenced by cranial biomechanics.
J Craniofac Surg
PUBLISHED: 05-21-2010
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Spring cranioplasty is used in selected cases of craniosynostosis. A rabbit model was used to determine (1) if cranial biomechanics modify the expected rate of spring expansion, (2) the residual spring force in situ after cranial expansion, and (3) if the spring weakens during clinical use.
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Floral symmetry genes and the origin and maintenance of zygomorphy in a plant-pollinator mutualism.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-02-2010
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The evolution of floral zygomorphy is an important innovation in flowering plants and is thought to arise principally from specialization on various insect pollinators. Floral morphology of neotropical Malpighiaceae is distinctive and highly conserved, especially with regard to symmetry, and is thought to be caused by selection by its oil-bee pollinators. We sought to characterize the genetic basis of floral zygomorphy in Malpighiaceae by investigating CYCLOIDEA2-like (CYC2-like) genes, which are required for establishing symmetry in diverse core eudicots. We identified two copies of CYC2-like genes in Malpighiaceae, which resulted from a gene duplication in the common ancestor of the family. A likely role for these loci in the development of floral zygomorphy in Malpighiaceae is demonstrated by the conserved pattern of dorsal gene expression in two distantly related neotropical species, Byrsonima crassifolia and Janusia guaranitica. Further evidence for this function is observed in a Malpighiaceae species that has moved to the paleotropics and experienced coincident shifts in pollinators, floral symmetry, and CYC2-like gene expression. The dorsal expression pat-tern observed in Malpighiaceae contrasts dramatically with their actinomorphic-flowered relatives, Centroplacaceae (Bhesa paniculata) and Elatinaceae (Bergia texana). In particular, B. texana exhibits a previously undescribed pattern of uniform CYC2 expression, suggesting that CYC2 expression among the actinomorphic ancestors of zygomorphic lineages may be much more complex than previously thought. We consider three evolutionary models that may have given rise to this patterning, including the hypothesis that floral zygomorphy in Malpighiaceae arose earlier than standard morphology-based character reconstructions suggest.
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Effects of ethnicity and insurance status on outcomes after thoracic endoluminal aortic aneurysm repair (TEVAR).
J. Vasc. Surg.
PUBLISHED: 03-30-2010
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Thoracic endoluminal aortic aneurysm repair (TEVAR) is associated with improved outcomes compared with open thoracic aortic aneurysm repair. This study was designed to better characterize TEVAR outcomes in a large population, and to determine if outcomes are independently influenced by patient ethnicity and insurance status.
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Impact of age, gender, and race on circulating ?? T cells.
Hum. Immunol.
PUBLISHED: 03-26-2010
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A major subset of human peripheral blood ?? T cells expresses the V?2V?2 T cell receptor and responds to malignant or infectious diseases. We noted significant differences in the numbers of V?2V?2 T cells in blood samples from healthy Caucasian CA or African American (AA) donors. On average, CA donors had 3.71% ± 4.37% V?2 cells (as a percentage of total lymphocytes) compared with 1.18% ± 2.14% V?2 cells for AA donors (p < 0.0001). Age and race had the greatest impact on V?2 cell levels; the effect of age was similar for both racial groups. The V?2 cell population was dominated, for both donor groups, by cells expressing the V?2-J?1.2 V?2 T cell receptor, an apparent result of strong positive selection and there was substantial overlap in the public V?2 clonotypes from both racial groups. Mechanisms for selection and amplification of V?2 cells are nearly identical for both groups, despite the significant difference in baseline levels. These data show that appropriate controls, matched for age and race, may be required for clinical studies of V?2V?2 T cells in infectious disease or cancer and raise important questions about the mechanisms regulating the levels of circulating V?2 cells.
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The biomechanical characteristics of cranial sutures are altered by spring cranioplasty forces.
Plast. Reconstr. Surg.
PUBLISHED: 03-26-2010
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The mechanical properties of the pediatric craniofacial complex allow dissipation of spring cranioplasty forces. Springs do not fully expand in situ and continue to transmit a continuous force until removal. The authors wished to investigate whether ongoing forces altered the biomechanical characteristics of cranial sutures.
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Cranial bone and suture strains incident to spring-assisted cranioplasty.
Plast. Reconstr. Surg.
PUBLISHED: 03-26-2010
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Spring-assisted cranioplasty transmits forces throughout the craniofacial complex that can be measured as strain. The strain magnitude in relation to normal background physiologic strains and the distribution of these strains are currently unknown.
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Favorable climate change response explains non-native species success in Thoreaus woods.
PLoS ONE
PUBLISHED: 01-26-2010
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Invasive species have tremendous detrimental ecological and economic impacts. Climate change may exacerbate species invasions across communities if non-native species are better able to respond to climate changes than native species. Recent evidence indicates that species that respond to climate change by adjusting their phenology (i.e., the timing of seasonal activities, such as flowering) have historically increased in abundance. The extent to which non-native species success is similarly linked to a favorable climate change response, however, remains untested. We analyzed a dataset initiated by the conservationist Henry David Thoreau that documents the long-term phenological response of native and non-native plant species over the last 150 years from Concord, Massachusetts (USA). Our results demonstrate that non-native species, and invasive species in particular, have been far better able to respond to recent climate change by adjusting their flowering time. This demonstrates that climate change has likely played, and may continue to play, an important role in facilitating non-native species naturalization and invasion at the community level.
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Pharmacotherapy of HIV-1 Infection: Focus on CCR5 Antagonist Maraviroc.
Clin Med Ther
PUBLISHED: 11-19-2009
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Sustained inhibition of HIV-1, the goal of antiretroviral therapy, is often impeded by the emergence of viral drug resistance. For patients infected with HIV-1 resistant to conventional drugs from the viral reverse transcriptase and protease inhibitor classes, the recently approved entry and integration inhibitors effectively suppress HIV-1 and offer additional therapeutic options. Entry inhibitors are particularly attractive because, unlike conventional antiretrovirals, they target HIV-1 extracellularly, thereby sparing cells from both viral- and drug-induced toxicities. The fusion inhibitor enfuvirtide and the CCR5 antagonist maraviroc are the first entry inhibitors licensed for patients with drug-resistant HIV-1, with maraviroc restricted to those infected with CCR5-tropic HIV-1 (R5 HIV-1) only. Vicriviroc (another CCR5 antagonist) is in Phase III clinical trials, whereas the CCR5 antibodies PRO 140 and HGS 004 are in early stages of clinical development. Potent antiviral synergy between maraviroc and CCR5 antibodies, coupled with distinct patterns of resistance, suggest their combinations might be particularly effective in patients. In addition, given that oral administration of maraviroc achieves high drug levels in cervicovaginal fluid, combinations of maraviroc and other CCR5 inhibitors could be effective in preventing HIV-1 transmission. Moreover, since CCR5 antagonists prevent rejection of transplanted organs, maraviroc could both suppress HIV-1 and prolong organ survival for the growing number of HIV-1 patients with kidney or liver failure necessitating organ transplantation. Thus, maraviroc offers an important treatment option for patients with drug-resistant R5 HIV-1, who presently account for >50% of drug-resistance cases.
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Viral load decay in antiretroviral-naïve patients receiving once-daily tenofovir and emtricitabine plus twice-daily nevirapine.
HIV Clin Trials
PUBLISHED: 11-13-2009
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The once-daily nucleoside reverse transcriptase inhibitor backbone of tenofovir and emtricitabine has been proven effective in combination with efavirenz and protease inhibitors in large clinical trials. This study evaluated tenofovir and emtricitabine in combination with nevirapine.
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Surgical management of craniofacial and skull base rhabdomyosarcomas.
J Craniofac Surg
PUBLISHED: 10-10-2009
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Craniofacial and skull base rhabdomyosarcomas (RMSs) are rare. Surgeons are involved both in the resection and the reconstruction of these tumors and in the management of late sequelae of earlier treatment. These tumors are highly heterogeneous, and the initial presentation may be insidious. We wished to determine how diagnostic difficulties could be overcome and how management outcomes could be optimized.
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Structure of the amyloid-beta (1-42) monomer absorbed to model phospholipid bilayers: a molecular dynamics study.
J Phys Chem B
PUBLISHED: 10-08-2009
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The amyloid-beta (Abeta) peptide, the 39 to 43 amino acid peptide that plays a substantial role in Alzheimers disease, has been shown to interact strongly with lipids both in vitro and in vivo. Abeta-lipid interactions have been proposed as a considerable factor in accelerating Abeta aggregation through the templating role of membranes in aggregation disorders. Previous work has shown that anionic lipids are able to significantly increase Abeta aggregation rate and induce a structural conversion in Abeta from a random coil to a beta-structure that is similar to the monomer structure observed in mature fibrils. However, it is unclear if this structural change occurs with the Abeta monomer because of direct interactions with the lipids or if the structural change results from protein-protein interactions during oligomerization. We use extensive replica exchange molecular dynamics simulations of an Abeta monomer bound to a homogeneous model zwitterionic or anionic lipid bilayer. From these simulations, we do not observe any significant beta-structure formation except for a small, unstable beta-hairpin formed on the anionic dioleylphosphatidylserine bilayer. Further, we see that the Asp23-Lys28 salt bridge that plays a role in beta-hairpin formation is not substantially formed on the bilayer surface and that Lys28 preferentially interacts with lipids when bound to the bilayer. These results suggest that the structural conversion seen in experiments are not due to the ordering of monomeric Abeta on the bilayer surface but are a result of protein-protein interactions enhanced by Abeta binding to the cell membrane.
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Avian influenza virus A (H5N1), detected through routine surveillance, in child, Bangladesh.
Emerging Infect. Dis.
PUBLISHED: 09-16-2009
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We identified avian influenza virus A (H5N1) infection in a child in Bangladesh in 2008 by routine influenza surveillance. The virus was of the same clade and phylogenetic subgroup as that circulating among poultry during the period. This case illustrates the value of routine surveillance for detection of novel influenza virus.
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Interaction of macrolide antibiotics with intestinally expressed human and rat organic anion-transporting polypeptides.
Drug Metab. Dispos.
PUBLISHED: 09-09-2009
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The macrolide antibiotics azithromycin and clarithromycin are large molecular weight compounds that exhibit moderate to excellent oral bioavailability in preclinical species and humans. Previous concomitant dosing studies in rats using rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor, suggested that the high oral absorption of azithromycin and clarithromycin may be caused by facilitative uptake by intestinal Oatps. In this study, we used OATP/Oatp-expressing cells to investigate the interaction of macrolides with rat Oatp1a5, human OATP1A2, and human/rat OATP2B1/Oatp2b1. These experiments showed that azithromycin and clarithromycin were potent inhibitors of rat Oatp1a5-mediated taurocholate uptake with apparent inhibitor constant (K(i)) values of 3.3 and 2.4 microM, respectively. The macrolides functioned as noncompetitive inhibitors but were not transport substrates for rat Oatp1a5, as assessed by direct uptake measurements of radiolabeled azithromycin and clarithromycin. cis-Inhibition and direct uptake studies further showed that azithromycin and clarithromycin were only very weak inhibitors and not substrates for human OATP1A2 and human/rat OATP2B1/Oatp2b1. In summary, these results indicate that the macrolides azithromycin and clarithromycin potently inhibit rat Oatp1a5 but do not significantly interact with OATP1A2 and OATP2B1/Oatp2b1. These intestinally expressed OATP/Oatp(s) are not responsible for the postulated facilitative uptake of azithromycin and clarithromycin, and alternative facilitative pathways must exist for their intestinal absorption.
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Malpighiales phylogenetics: Gaining ground on one of the most recalcitrant clades in the angiosperm tree of life.
Am. J. Bot.
PUBLISHED: 08-01-2009
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The eudicot order Malpighiales contains ?16000 species and is the most poorly resolved large rosid clade. To clarify phylogenetic relationships in the order, we used maximum likelihood, Bayesian, and parsimony analyses of DNA sequence data from 13 gene regions, totaling 15604 bp, and representing all three genomic compartments (i.e., plastid: atpB, matK, ndhF, and rbcL; mitochondrial: ccmB, cob, matR, nad1B-C, nad6, and rps3; and nuclear: 18S rDNA, PHYC, and newly developed low-copy EMB2765). Our sampling of 190 taxa includes representatives from all families of Malpighiales. These data provide greatly increased support for the recent additions of Aneulophus, Bhesa, Centroplacus, Ploiarium, and Rafflesiaceae to Malpighiales; sister relations of Phyllanthaceae + Picrodendraceae, monophyly of Hypericaceae, and polyphyly of Clusiaceae. Oxalidales + Huaceae, followed by Celastrales are successive sisters to Malpighiales. Parasitic Rafflesiaceae, which produce the worlds largest flowers, are confirmed as embedded within a paraphyletic Euphorbiaceae. Novel findings show a well-supported placement of Ctenolophonaceae with Erythroxylaceae + Rhizophoraceae, sister-group relationships of Bhesa + Centroplacus, and the exclusion of Medusandra from Malpighiales. New taxonomic circumscriptions include the addition of Bhesa to Centroplacaceae, Medusandra to Peridiscaceae (Saxifragales), Calophyllaceae applied to Clusiaceae subfamily Kielmeyeroideae, Peraceae applied to Euphorbiaceae subfamily Peroideae, and Huaceae included in Oxalidales.
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First isolation of an H1N1 avian influenza virus from wild terrestrial non-migratory birds in Argentina.
Virology
PUBLISHED: 07-30-2009
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A type A avian influenza (AI) virus was isolated from dead or severely ill red-winged tinamous (Rhynchotus rufescens) found in a hunting ground in April 2008 in Argentina. The subtype of A/red-winged tinamou/Argentina/MP1/2008 was determined as H1N1 by sequence analysis. The cleavage site of the viral hemagglutinin corresponded to a low pathogenic influenza virus, although the clinical presentation and pathological studies suggest that the virus was pathogenic for red-winged tinamous. Phylogenetic analysis of the viral genome suggested that while the hemagglutinin and neuraminidase genes were related to AIV from North America, the internal genes were most closely related to other South American isolates. These findings support the postulated South American phylogenetic lineage for AIV PB2, PB1, PA, M and NS genes, and suggest that the evolutionary pathways of HA and NA genes involve exchanges between the Northern and Southern hemispheres.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.