Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 ?l), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Digital platform and open resources on restorative justice

Se explica la elaboración de una plataforma digital sobre justicia restaurativa de la UCM, continuando los Proyectos de Innovación precedentes sobre la misma temática y con el fin de digitalizar el contenido precedente. El proyecto posee en dos dimensiones: de un lado, la formativa, que ha consistido en asegurar la formación teórico-práctica de los alumnos en materia de justicia restaurativa a través de la estrategia Aprendizaje y Servicio y contando con la red de contactos que hemos confeccionado a lo largo de estos años, apostando por la enseñanza virtual y la internacionalización. Por otro lado, se encuentra la dimensión estrictamente innovadora, pues el proyecto implica apostar por innovación de recursos en abierto y enseñanza virtual, confeccionando la plataforma digital sobre el tema que ha vertebrado sobre dos iniciativas: la creación de un MOOC por parte de alumnos y profesores y la puesta en marcha de una Web dentro de la UCM con material disponible y publico sobre esta dimensión tan importante de la justicia, enmarcándola dentro de todos los programas universitarios centrados en la Agenda 2030.The development of a digital platform on restorative justice of the UCM is explained, continuing the preceding Innovation Projects on the same theme and aiming to digitize the preceding content. The project possesses two dimensions: on the one hand, the formative, which has consisted of ensuring the theoretical-practical training of pupils in restorative justice through the Learning and Service strategy and counting on the network of contacts we have made throughout these years, betting on virtual teaching and internationalization. On the other hand, the strictly innovative dimension is found, as the project involves betting on open resource innovation and virtual teaching, making the digital platform on the theme that has vertebrated on two initiatives: the creation of a MOOC by students and professors and the launch of a Web site within UCM with available and public material on this so important dimension of justice, framing it within all university programs centered on the 2030 Agenda.Depto. de Derecho Internacional, Eclesiástico y Filosofía del DerechoFac. de DerechoFALSEsubmitte

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (?10 wbc/?l) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/?l). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ?80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

El derecho del trabajo y de la seguridad social en españa en 2018

En su quinta edición, el Informe “El Derecho del Trabajo y de la Seguridad Social en España 2018” le ofrece una síntesis, que por concreta no es menos rigurosa, de los principales hitos por los que ha transitado el iuslaboralismo a lo largo del último año. En concreto, en las páginas que siguen, los expertos integrantes de la Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social (AEDTSS) analizan para usted, en primer lugar, las principales resoluciones europeas y nacionales en materia de igualad y no discriminación, acoso en sus más diversas manifestaciones, liberad religiosa y libertad de expresión. Asimismo, se abordan también las cuestiones relativas al empleo y la contratación, casi monopolizadas por el impacto de las plataformas y las consecuencias del caso de Diego. En materia de vicisitudes, sin perder importancia el despido colectivo, observará un cierto auge de los casos relativos a sucesión empresarial, movilidad funcional y empleo público. En el ámbito del derecho colectivo, además de analizarse el IV AENC, encontrará un estudio pormenorizado de las principales resoluciones en materia de libertad sindical, representación unitaria y ultraactividad. La sección relativa a conciliación y corresponsabilidad incluye este año como novedad un apartado relativo a violencia de género, al hilo de los avances normativos derivados del Real Decreto-ley 9/2018. Los epígrafes concernientes a la protección social y la prevención de riesgos laborales crecen de forma significativa en esta edición, lo que ha permitido abordar la evolución jurisprudencial para buena parte de las prestaciones y riesgos previstos en la Ley. Por último, las expertas del apartado de derecho procesal se han encargado de revisar a fondo los casos más significativos en el marco de las modalidades procesales especiales, con especial hincapié en el ámbito concursal. También han abordado la jurisprudencia constitucional más reciente sobre el de recurso de reposición. En suma, tienen ante usted un trabajo científico consolidado en el tiempo y sólido en cuanto al contenido, fiel reflejo de, a pesar del difícil contexto, el buen hacer de la joven doctrina iuslaboralista española

El Derecho del Trabajo y de la Seguridad Social en España en 2016. Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social

En su quinta edición, el Informe “El Derecho del Trabajo y de la Seguridad Social en España 2018” le ofrece una síntesis, que por concreta no es menos rigurosa, de los principales hitos por los que ha transitado el iuslaboralismo a lo largo del último año. En concreto, en las páginas que siguen, los expertos integrantes de la Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social (AEDTSS) analizan para usted, en primer lugar, las principales resoluciones europeas y nacionales en materia de igualad y no discriminación, acoso en sus más diversas manifestaciones, liberad religiosa y libertad de expresión. Asimismo, se abordan también las cuestiones relativas al empleo y la contratación, casi monopolizadas por el impacto de las plataformas y las consecuencias del caso de Diego. En materia de vicisitudes, sin perder importancia el despido colectivo, observará un cierto auge de los casos relativos a sucesión empresarial, movilidad funcional y empleo público. En el ámbito del derecho colectivo, además de analizarse el IV AENC, encontrará un estudio pormenorizado de las principales resoluciones en materia de libertad sindical, representación unitaria y ultraactividad. La sección relativa a conciliación y corresponsabilidad incluye este año como novedad un apartado relativo a violencia de género, al hilo de los avances normativos derivados del Real Decreto-ley 9/2018. Los epígrafes concernientes a la protección social y la prevención de riesgos laborales crecen de forma significativa en esta edición, lo que ha permitido abordar la evolución jurisprudencial para buena parte de las prestaciones y riesgos previstos en la Ley. Por último, las expertas del apartado de derecho procesal se han encargado de revisar a fondo los casos más significativos en el marco de las modalidades procesales especiales, con especial hincapié en el ámbito concursal. También han abordado la jurisprudencia constitucional más reciente sobre el de recurso de reposición. En suma, tienen ante usted un trabajo científico consolidado en el tiempo y sólido en cuanto al contenido, fiel reflejo de, a pesar del difícil contexto, el buen hacer de la joven doctrina iuslaboralista española. The fifth edition of the report, "Labour and Social Security Law in Spain in 2018" analyses the key issues in the changing scenario of Labour Law and Social Security during last year. Elaborated by the Young Scholars’ Section of the Spanish Association of Labour and Social Security Law focuses on the following thematic blocks: non-specific fundamental rights; employment contracts and employment; issues related to employment relationship; collective rights; equality and co-responsibility; occupational risks prevention; and procedural law. In conclusion, you may find here a concrete but detailed analysis of the the main legal and case law novelties of Spanish Social Law

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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