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1.
Artículo en Inglés | MEDLINE | ID: mdl-36483360

RESUMEN

Antibiotic stewardship initiatives usually occur in the inpatient setting and should be optimized during transitions of care. In this study, we assessed the appropriateness of oral antibiotic treatment duration at the time of discharge from our institution based on national guidelines and clinical parameters for common infections.

2.
Biol Open ; 9(8)2020 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32855167

RESUMEN

The mouse T-box transcription factors T and Tbx6 are co-expressed in the primitive streak and have unique domains of expression; T is expressed in the notochord, while Tbx6 is expressed in the presomitic mesoderm. T-box factors are related through a shared DNA binding domain, the T-domain, and can therefore bind to similar DNA sequences at least in vitro We investigated the functional similarities and differences of T and Tbx6 DNA binding and transcriptional activity in vitro and their interaction genetically in vivo We show that at one target, Dll1, the T-domains of T and Tbx6 have different affinities for the binding sites present in the mesoderm enhancer. We further show using in vitro assays that T and Tbx6 differentially affect transcription with Tbx6 activating expression tenfold higher than T, that T and Tbx6 can compete at target gene enhancers, and that this competition requires a functional DNA binding domain. Next, we addressed whether T and Tbx6 can compete in vivo First, we generated embryos that express Tbx6 at greater than wild-type levels embryos and show that these embryos have short tails, resembling the T heterozygous phenotype. Next, using the dominant-negative TWis allele, we show that Tbx6+/- TWis/+ embryos share similarities with embryos homozygous for the Tbx6 hypomorphic allele rib-vertebrae, specifically fusions of several ribs and malformation of some vertebrae. Finally, we tested whether Tbx6 can functionally replace T using a knockin approach, which resulted in severe T null-like phenotypes in chimeric embryos generated with ES cells heterozygous for a Tbx6 knockin at the T locus. Altogether, our results of differences in affinity for DNA binding sites and transcriptional activity for T and Tbx6 provide a potential mechanism for the failure of Tbx6 to functionally replace T and possible competition phenotypes in vivo.


Asunto(s)
Desarrollo Embrionario , Proteínas Fetales/metabolismo , Proteínas de Dominio T Box/metabolismo , Alelos , Animales , Secuencia de Bases , Sitios de Unión , Embrión de Mamíferos/anomalías , Embrión de Mamíferos/metabolismo , Elementos de Facilitación Genéticos/genética , Proteínas Fetales/química , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Humanos , Luciferasas/metabolismo , Ratones , Fenotipo , Dominios Proteicos , Proteínas de Dominio T Box/química , Transcripción Genética , Regulación hacia Arriba/genética
3.
IDCases ; 13: 4, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30181953

RESUMEN

Since its identification as a unique species in 1982, Escherichia hermannii has been implicated as a pathogenic organism in very few cases of human disease. Our report discusses a case of bacteremia with Escherichia hermannii identified by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and RapID™ ONE analysis in a patient getting TPN through a peripherally-inserted CVC (PICC). The PICC was removed. The bloodstream infection was successfully treated with empiric piperacillin-tazobactam, which was then narrowed to trimethoprim-sulfamethoxazole based on sensitivity data for a 14 day course of antimicrobial therapy. E. hermannii's association with bloodstream infection in patients with central venous catheters supports data implicating biofilm formation as a key pathogenic feature of E. hermannii. Of the 9 previous cases of E. hermannii infection reviewed in the literature, 4 cases occurred in immunocompromised hosts, 2 were associated with trauma or injection, 2 were associated with central lines, and only one case had no identifiable risk factor. E. hermannii appears to act as an opportunistic pathogen, causing disease in an immunocompromised host or through a central access catheter, injection, or trauma. E. hermannii likely causes catheter-related bloodstream infections in these hosts through biofilm formation, demonstrating the importance of catheter removal in addition to antimicrobial therapy in the treatment of these infections.

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