Unique Features of Alarmone Metabolism in Clostridioides difficile.

The "magic spot" alarmones (pp)pGpp, previously implicated in Clostridioides difficile antibiotic survival, are synthesized by the RelA-SpoT homolog (RSH) of C. difficile (RSHCd) and RelQCd. These enzymes are transcriptionally activated by diverse environmental stresses. RSHCd has previously been reported to synthesize ppGpp, but in this study, we found that both clostridial enzymes exclusively synthesize pGpp. While direct synthesis of pGpp from a GMP substrate, and (p)ppGpp hydrolysis into pGpp by NUDIX hydrolases, have previously been reported, there is no precedent for a bacterium synthesizing pGpp exclusively. Hydrolysis of the 5' phosphate or pyrophosphate from GDP or GTP substrates is necessary for activity by the clostridial enzymes, neither of which can utilize GMP as a substrate. Both enzymes are remarkably insensitive to the size of their metal ion cofactor, tolerating a broad array of metals that do not allow activity in (pp)pGpp synthetases from other organisms. It is clear that while C. difficile utilizes alarmone signaling, its mechanisms of alarmone synthesis are not directly homologous to those in more completely characterized organisms. IMPORTANCE Despite the role of the stringent response in antibiotic survival and recurrent infections, it has been a challenging target for antibacterial therapies because it is so ubiquitous. This is an especially relevant consideration for the treatment of Clostridioides difficile infection (CDI), as exposure to broad-spectrum antibiotics that harm commensal microbes is a major risk factor for CDI. Here, we report that both of the alarmone synthetase enzymes that mediate the stringent response in this organism employ a unique mechanism that requires the hydrolysis of two phosphate bonds and synthesize the triphosphate alarmone pGpp exclusively. Inhibitors targeted against these noncanonical synthetases have the potential to be highly specific and minimize detrimental effects to stringent response pathways in commensal microbes.

Adecuación de estancias e ingresos en un hospital pediátrico / Adequacy of the stays and admissions in a pediatric hospital

Fundamento y objetivo: El aumento constante de la demanda asistencial en los servicios de hospitalización general, y más concretamente en los servicios pediátricos, justifica el interés por conocer su situación real en relación con las necesidades de atención pediátrica por parte de la población. El objetivo de este estudio es determinar la adecuación de las estancias e ingresos del Hospital Infantil «La Fe» (Valencia). Materiales y métodos: Estudio transversal descriptivo con componentes analíticos. La unidad de análisis fue un día de hospitalización (13 de mayo de 2007) ante los informes de alta del servicio de urgencias generales de dicho hospital durante la tercera semana de octubre de 2007, a los que se aplicó la versión pediátrica del protocolo de adecuación de ingresos y estancias PAEP (Paediatric Appropriateness Evaluation Protocol).Resultados: El porcentaje de inadecuación de ingresos fue del 10,5% y el de inadecuación de las estancias del 18,4%. La causa más frecuente de inadecuación de los ingresos fueron «las necesidades diagnósticas y terapéuticas pueden ser realizadas como paciente externo». La causa más frecuente de inadecuación de estancias fueron los «problemas de programación de pruebas o procedimientos quirúrgicos». Discusión: Confirmamos la hipótesis de la existencia de hospitalizaciones innecesarias en pediatría. El porcentaje de ingresos y estancias inadecuados fue similar al de otros estudios. El protocolo PAEP resultó ser un instrumento fácil de utilizar. El conocimiento de los factores de riesgo para los ingresos y las estancias inadecuados nos permitirá establecerlas medidas correctoras para optimizar la utilización de los recursos hospitalarios pediátricos en nuestro medio (AU)

Foundation and objective: The constant increase of the welfare demand in the departments of general hospitalization and more concretely in the pediatric department justifies the interest to know its real situation in relation to the needs of pediatric attention by part of the population. The objective of this study is to determine the adequacy of the stays and admissions of the infantile hospital La Fe (Valencia).Materials and methods: Transverse descriptive study with analytical components. The unit of analysis was a day of hospitalization (05/13/2007) before the reports of discharge of the general emergency unit of the infantile hospital La Fe during the third week of October 2007, to those to whom the pediatric version of the protocol of adequacy of admissions and stays (Pediatric Appropriateness Evaluation Protocol) PAEP was applied. Results: The inadequacy of admissions was of 10.5%. The percentage of inadequacy of stays was of 18.4 %. The more frequent reason of inadequacy of admissions was “the diagnostic and therapeutic needs can be conducted as external patient”. The most frequent reason of inadequacy of stays was “problems of programming test or surgical procedures”. Discussion: We confirm the hypothesis of the existence of unnecessary hospitalization in pediatrics. The percentage of inadequate admissions and stays was similar to that of other studies. The procotol PAEP turned out to be an easy to use instrument. The knowledge of the risk factors for inadequate admissions and stays will allow us to introduce correcting measures to optimize the use of the hospital pediatric resources in environment (AU)

¿Está justificado el cribado de aneurisma de aorta abdominal en pacientes con hernia inguinal? Estudio de prevalencia en la Comunidad Asturiana / Is abdominal aortic aneurysm screening justified in patients suffering from inguinal hernia? A prevalence study in the Asturian Community

Introducción. La importancia de la detección precoz de los aneurismas de aorta abdominal (AAA) como mediode reducir la elevada morbimortalidad asociada a su rotura, se encuentra ampliamente reconocida, especialmente engrupos de riesgo. Objetivo. Determinar si la hernia inguinal (HI) debe considerarse un factor de riesgo para el desarrollode un AAA. Sujetos y métodos. Se diseñó un estudio de casos y controles, prospectivo y muticéntrico en la comunidadasturiana. Se comparó 291 pacientes que iban a ser intervenidos por HI con 459 controles, obtenidos de la misma población(varones de 50 o más años de edad). La definición de AAA fue la de un diámetro máximo mayor o igual a 30 mm medidoscon ecografía. Se evaluó la asociación entre HI y AAA. Resultados. Se realizó un total de 750 ecografías abdominales,obteniéndose una prevalencia similar de AAA en ambos grupos: 3,8% en el grupo de pacientes con HI y 3,5% enel grupo control. Conclusiones. De acuerdo con los resultados, no podemos confirmar una asociación positiva entre AAAy HI; por lo tanto, con los datos presentes, no se puede justificar el cribado selectivo de pacientes con HI para la detecciónprecoz de AAA

Introduction. Early detection of abdominal aortic aneurysms is broadly accepted as a prominent issue toreduce the high morbimortality rates results from ruptured AAAs, especially in high-risk population. Aim. To estimatewhether inguinal hernia (IH) must be considered as a risk factor for the development of an abdominal aortic aneurysm(AAA). Subjects and methods. A multi centric, prospective case-control study was designed. 291 patients suffering fromIH expecting surgical repair were compared with 459 controls. We seek to evaluate the association between AAA and IH.AAA is defined by a maximum aortic diameter of 30 mm or more measured by ultrasonography. All male aged 50-yearsoldor older subjects were recruited from a single population. Results. An overall 750 abdominal duplex-scans wereperformed. We found a similar prevalence of AAA in both groups: 3.8 % for the hernia group and 3.5 % for the controls.Conclusion. According to the results, we can not confirm a positive association between AAA and IH. Thus, present datado not support selective screening in patients with IH for an early AAA detection

Aneurismas de aorta abdominal. Perspectivas de futuro

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[Cardiovascular risk factors in peripheral arterial disease. A study of 403 cases]. / Factores de riesgo cardiovascular en la enfermedad arterial periférica. Estudio de 403 casos.

We studied the prevalence of risk factors and related cardiovascular complications in 403 patients with periferal arterial disease (PAD) arising from atherosclerosis. The control group was made up of 126 patients of the same age and sex and without PAD. The average age was 66.9 +/- 12 years, and the percentage of men was 80%. Among the male subjects, smoking, the presence of diabetes, total cholesterol count, and age were the prevalent risk factors, even after logistic regression analysis. Among women, only smoking and diabetes showed significant differences. Among both sexes, the prevalence of arterial hypertension was similar to that of the controls. Greater prevalence of related cardiovascular complications was found only in men. We conclude that for PAD, smoking and diabetes are the most important cardiovascular risk factors, with total cholesterol level being an important additional factor in men.

[Epidemiology of critical ischemia of the limbs]. / Epidemiología de la isquemia crítica de las extremidades.

Authors report their results from a study made during 1991. The study was made in order to analyze the clinical complications (morbidity and mortality) and the socioeconomic consequences that are related to the cure of patients with highly developed ischemic diseases (critical ischemia). Economic expenses mean a 1.5% from the total budget of the Public Sanity into the Asturian Autonomic Community.