¿Es útil la estratificación de la sensibilidad antibiótica de los patógenos urinarios en el Servicio de Urgencias? / Is stratification of antibiotic susceptibility of urinary pathogens useful in the Emergency Department?

OBJETIVO: Determinar la sensibilidad antibiótica de los patógenos causantes de infección del tracto urinario (ITU) estratificándola en función de datos clínicos y demográficos de los pacientes. MATERIAL Y MÉTODOS: Se analizó sensibilidad antibiótica de las bacterias aisladas en orina de 144 pacientes con ITU escogidos al azar y se estratificó en función del sexo, la edad, el tipo de ITU, el haber padecido o no ITU previa y del tratamiento antibiótico previo. RESULTADOS: Se analizó la sensibilidad global de todas las cepas y de las cepas de E. coli observándose diferencias significativas en función del sexo (fluoroquinolonas), la edad (cefuroxima, ertapenem, gentamicina), el tipo de ITU (cefuroxima, cefotaxima, ertapenem, fluoroquinolonas), el haber tenido ITU previa y antibioterapia previa (cefotaxima, fluoroquinolonas, fosfomicina). CONCLUSIONES: El empleo de datos clínicos y demográficos adaptados a la población y a la epidemiología local de resistencia de los uropatógenos, podría ayudar a la elección del tratamiento empírico de la ITU

OBJECTIVE: The aim of the study wat to analyze the antibiotic susceptibility of the pathogens causing urinary tract infection (UTI) and to stratify the results in function of patient's clinical and demographic dates. MATERIAL AND METHODS: The susceptibility of the pathogens isolated in the urine of 144 patients with UTI randomly chosen was analyzed. The results were stratified in function of sex, age, type of UTI, previous UTI and previous antibiotic treatment. RESULTS: The susceptibility of the all isolates and of the Escherichia coli isolates was analyzed. There were significant differences between groups in function of sex (fluoroquinolones), age (cefuroxime, ertapenem and gentamicin), type of UTI (cefuroxime, cefotaxime, ertapenem and fluoroquinolones), previous UTI and previous antibiotic treatment (cefotaxime, fluoroquinolones and fosfomycin). CONCLUSIONS: The use of clinical and demographic data according to population and local resistance epidemiology of the pathogen causing UTI may help to select an adequate empirical treatment for UTI

The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth.

The Hippo signalling pathway restricts cell proliferation in animal tissues by inhibiting Yes-associated protein (YAP or YAP1) and Transcriptional Activator with a PDZ domain (TAZ or WW-domain-containing transcriptional activator [WWTR1]), coactivators of the Scalloped (Sd or TEAD) DNA-binding transcription factor. Drosophila has a single YAP/TAZ homolog named Yorkie (Yki) that is regulated by Hippo pathway signalling in response to epithelial polarity and tissue mechanics during development. Here, we show that Yki translocates to the nucleus to drive Sd-mediated cell proliferation in the ovarian follicle cell epithelium in response to mechanical stretching caused by the growth of the germline. Importantly, mechanically induced Yki nuclear localisation also requires nutritionally induced insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) via phosphatidyl inositol-3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1 or PDPK1), and protein kinase B (Akt or PKB) in the follicular epithelium. We find similar results in the developing Drosophila wing, where Yki becomes nuclear in the mechanically stretched cells of the wing pouch during larval feeding, which induces IIS, but translocates to the cytoplasm upon cessation of feeding in the third instar stage. Inactivating Akt prevents nuclear Yki localisation in the wing disc, while ectopic activation of the insulin receptor, PI3K, or Akt/PKB is sufficient to maintain nuclear Yki in mechanically stimulated cells of the wing pouch even after feeding ceases. Finally, IIS also promotes YAP nuclear localisation in response to mechanical cues in mammalian skin epithelia. Thus, the Hippo pathway has a physiological function as an integrator of epithelial cell polarity, tissue mechanics, and nutritional cues to control cell proliferation and tissue growth in both Drosophila and mammals.

Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability.

Mask family proteins were discovered in Drosophila to promote the activity of the transcriptional coactivator Yorkie (Yki), the sole fly homolog of mammalian YAP (YAP1) and TAZ (WWTR1). The molecular function of Mask, or its mammalian homologs Mask1 (ANKHD1) and Mask2 (ANKRD17), remains unclear. Mask family proteins contain two ankyrin repeat domains that bind Yki/YAP as well as a conserved nuclear localisation sequence (NLS) and nuclear export sequence (NES), suggesting a role in nucleo-cytoplasmic transport. Here we show that Mask acts to promote nuclear import of Yki, and that addition of an ectopic NLS to Yki is sufficient to bypass the requirement for Mask in Yki-driven tissue growth. Mammalian Mask1/2 proteins also promote nuclear import of YAP, as well as stabilising YAP and driving formation of liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction.

Mechanical strain regulates the Hippo pathway in Drosophila.

Animal cells are thought to sense mechanical forces via the transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1), the sole Drosophila homolog of which is named Yorkie (Yki). In mammalian cells in culture, artificial mechanical forces induce nuclear translocation of YAP and TAZ. Here, we show that physiological mechanical strain can also drive nuclear localisation of Yki and activation of Yki target genes in the Drosophila follicular epithelium. Mechanical strain activates Yki by stretching the apical domain, reducing the concentration of apical Crumbs, Expanded, Kibra and Merlin, and reducing apical Hippo kinase dimerisation. Overexpressing Hippo kinase to induce ectopic activation in the cytoplasm is sufficient to prevent Yki nuclear localisation even in flattened follicle cells. Conversely, blocking Hippo signalling in warts clones causes Yki nuclear localisation even in columnar follicle cells. We find no evidence for involvement of other pathways, such as Src42A kinase, in regulation of Yki. Finally, our results in follicle cells appear generally applicable to other tissues, as nuclear translocation of Yki is also readily detectable in other flattened epithelial cells such as the peripodial epithelium of the wing imaginal disc, where it promotes cell flattening.