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911.
912.
Sheliza Halani Panashe E. Tombindo Ryan OReilly Rafael N. Miranda Laura K. Erdman Clare Whitehead Joanna M. Bielecki Lauren Ramsay Raphael Ximenes Justin Boyle Carsten Krueger Shannon Willmott Shaun K. Morris Kellie E. Murphy Beate Sander 《PLoS neglected tropical diseases》2021,15(7)
BackgroundZika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally.MethodsThis review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools.FindingsWe identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS.ConclusionsThe ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae. 相似文献
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915.
Kuzmich D Kirrane T Proudfoot J Bekkali Y Zindell R Beck L Nelson R Shih CK Kukulka AJ Paw Z Reilly P Deleon R Cardozo M Nabozny G Thomson D 《Bioorganic & medicinal chemistry letters》2007,17(18):5025-5031
A new series of ligands for the glucocorticoid receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an unsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To identify compounds with an improved side effect profile over marketed steroids the functional activity of compounds was evaluated in cell based assays for transactivation (aromatase) and transrepression (IL-6). Through this effort, 36 has been identified as a partial agonist with a dissociated profile in these cell based assays. 相似文献
916.
Freeman-Cook KD Reiter LA Noe MC Antipas AS Danley DE Datta K Downs JT Eisenbeis S Eskra JD Garmene DJ Greer EM Griffiths RJ Guzman R Hardink JR Janat F Jones CS Martinelli GJ Mitchell PG Laird ER Liras JL Lopresti-Morrow LL Pandit J Reilly UD Robertson D Vaughn-Bowser ML Wolf-Gouviea LA Yocum SA 《Bioorganic & medicinal chemistry letters》2007,17(23):6529-6534
Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved by incorporation of an extended aryl-heteroaryl P1'group. When dosed as the sodium salt, these compounds displayed excellent oral absorption and pharmacokinetic properties. Despite the selectivity, a representative of this series produced fibroplasia in a 14 day rat study. 相似文献
917.
Norman BH Richardson TI Dodge JA Pfeifer LA Durst GL Wang Y Durbin JD Krishnan V Dinn SR Liu S Reilly JE Ryter KT 《Bioorganic & medicinal chemistry letters》2007,17(18):5082-5085
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERalpha, thus improving ERbeta subtype selectivity. X-ray cocrystal structures with ERalpha and ERbeta are supportive of this approach to improve selectivity in this structural class. 相似文献
918.
Reilly HB Wang H Steuter JA Marx AM Ferdig MT 《International journal for parasitology》2007,37(14):1599-1607
Measurement of parasite proliferation in cultured red blood cells underpins many facets of malaria research, from drug sensitivity assays to assessing the impact of experimentally altered genes on parasite growth, virulence and fitness. Pioneering efforts to grow Plasmodium falciparum in cultured red blood cells revolutionised malaria research and spurred the development of semi-high-throughput growth assays using radio-labelled hypoxanthine (Hx), an essential nucleic acid precursor, as a reporter of whole-cycle proliferation [Trager, W., Jensen, J.B., 1976. Human malaria parasites in continuous culture. Science 193, 673–675; Desjardins, R.E., Canfield, C.J., Haynes, J.D., Chulay, J.D., 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob. Agents Chemother. 16, 710–718]. The isotopic Hx assay remains the standard quantitative growth assay with which newer non-radioactive procedures based on fluorescent DNA dyes or ELISA are compared. All of these readouts are surrogate reporters of changes in bulk parasitemias, reflecting proliferation over entire asexual reproductive cycles. While quantitatively robust and amenable to semi-high-throughput applications, these methods are blind to the underlying developmental and cellular events of growth in human red blood cells. Modern whole-genome tools including gene knockouts, mutagenesis and small molecule screens promise to reveal much about basic parasite biology; however methods to precisely quantify the within-cycle growth process are needed. Here we elaborate on the classical growth index, i.e. changes in parasitemia, by quantifying sub-phenotypes of a rapid proliferator, the multi-drug resistant clone Dd2, and a standard wild-type clone, HB3. These data illustrate differences in cycle duration, merozoite production, and invasion rate and efficiency that underpin Dd2’s average 2-fold proliferation advantage over HB3 per erythrocytic cycle. The ability to refine growth phenotypes will inform the search for molecular determinants of differential parasite growth rates and broaden our understanding of killing mechanisms and cellular targets of antimalarial drugs. 相似文献
919.
Challacombe JF Altherr MR Xie G Bhotika SS Brown N Bruce D Campbell CS Campbell ML Chen J Chertkov O Cleland C Dimitrijevic M Doggett NA Fawcett JJ Glavina T Goodwin LA Green LD Han CS Hill KK Hitchcock P Jackson PJ Keim P Kewalramani AR Longmire J Lucas S Malfatti S Martinez D McMurry K Meincke LJ Misra M Moseman BL Mundt M Munk AC Okinaka RT Parson-Quintana B Reilly LP Richardson P Robinson DL Saunders E Tapia R Tesmer JG Thayer N Thompson LS Tice H Ticknor LO Wills PL Gilna P Brettin TS 《Journal of bacteriology》2007,189(9):3680-3681
Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003). 相似文献
920.
Claire Roddie Maeve OReilly Juliana Dias Alves Pinto Ketki Vispute Mark Lowdell 《Cytotherapy》2019,21(3):327-340
Clinical trials of adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have delivered unprecedented responses in patients with relapsed refractory B-cell malignancy. These results have prompted Food and Drug Administration (FDA) approval of two CAR T-cell products in this high-risk patient population. The widening range of indications for CAR T-cell therapy and increasing patient numbers present a significant logistical challenge to manufacturers aiming for reproducible delivery systems for high-quality clinical CAR T-cell products. This review discusses current and novel CAR T-cell processing methodologies and the quality control systems needed to meet the increasing clinical demand for these exciting new therapies. 相似文献