Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.Includes Wellcome, BHF, MRC, BBSRC and NIHR

Increasing incidence and mortality of infective endocarditis: a population-based study through a record-linkage system

<p>Abstract</p> <p>Background</p> <p>Few population-based studies provide epidemiological data on infective endocarditis (IE). Aim of the study is to analyze incidence and outcomes of IE in the Veneto Region (North-Eastern Italy).</p> <p>Methods</p> <p>Residents with a first hospitalization for IE in 2000-2008 were extracted from discharge data and linked to mortality records to estimate 365-days survival. Etiology was retrieved in subsets of this cohort by discharge codes and by linkage to a microbiological database. Risk factors for mortality were assessed through logistic regression.</p> <p>Results</p> <p>1,863 subjects were hospitalized for IE, with a corresponding crude rate of 4.4 per 100,000 person-years, increasing from 4.1 in 2000-2002 to 4.9 in 2006-2008 (p = 0.003). Median age was 68 years; 39% of subjects were hospitalized in the three preceding months. 23% of patients underwent a cardiac valve procedure in the index admission or in the following year. Inhospital mortality was 14% (19% including hospital transfers); 90-days and 365-days mortality rose through the study years. Mortality increased with age and the Charlson comorbidity index, in subjects with previous hospitalizations for heart failure, and (in the subcohort with microbiological data) in IE due to Staphylococci (40% of IE).</p> <p>Conclusions</p> <p>The study demonstrates an increasing incidence and mortality for IE over the last decade. Analyses of electronic archives provide a region-wide picture of IE, overcoming referral biases affecting single clinic or multicentric studies, and therefore represent a first fundamental step to detect critical issues related to IE.</p

Questões éticas envolvidas na prática profissional de enfermeiros da comissão de controle de infecção hospitalar Cuestiones éticas comprometidas en la práctica profesional de los enfermeros del comité de infecciones intrahospitalarias Ethical issues linked to the professional practice of nurses that are members of a hospital infection control commission

Este trabalho foi realizado segundo a metodologia qualitativa, utilizando-se o método da análise de conteúdo de Bardin(3). Objetivou-se resgatar, junto aos enfermeiros de Comissão de Controle de Infecção Hospitalar (CCIH), suas percepções sobre as questões éticas, inerentes a sua prática profissional; apreender, junto aos enfermeiros assistenciais, a visão deles em relação à prática profissional do enfermeiro da CCIH, tendo em vista os aspectos éticos. Como possibilidades de uma prática profissional ética, eficaz e eficiente, haveria a necessidade de transformações de cunho governamental, reconhecimento profissional por meio da autonomia, respeito e exclusividade no Serviço de Controle de Infecção Hospitalar, além de melhorias nos vários aspectos da informação, da assistência prestada ao paciente e do sigilo profissional. O predomínio de atividades burocráticas e o trabalho em equipe como fator diferenciador das atividades realizadas pelo enfermeiro da Comissão, foram aspectos relevantes apreendidos pelos enfermeiros assistenciais.<br>Este trabajo fue realizado según la metodología cualitativa, usando el método de análisis de contenido de Bardin(3). Relata las percepciones en relación con los aspectos éticos de la práctica profesional del enfermero del comité de infecciones intrahospitalarias. (CII), sus percepciones y expectativas en relación con la práctica profesional del enfermero de este comité, Como posibilidades de una práctica profesional ética, eficaz y eficiente, habría la necesidad de transformaciones gubernamentales, reconocimiento profesional por medio de la autonomía, respeto y exclusividad en el Servicio de Control de la Infección Intrahospitalaria, además de mejoras en muchos aspectos de la información, de la asistencia prestada al enfermo y del secreto profesional. El predominio de actividades burocráticas y el trabajo en equipo como factor diferenciado de las actividades realizadas por el enfermero del comité, fueron aspectos relevantes aprendidos por los enfermeros asistenciales.<br>This qualitative work was developed according to Bardin's(3) method of content analysis. It aimed at finding out the perceptions of nurses that are members of a Hospital Infection Control Commission about ethical issues that are inherent to their professional practice as well as understanding the clinical nurses opinion regarding the professional practice of the nurses that are members of the Hospital Infection Control Commission, considering the ethical aspects. In order to achieve an ethical, efficient and effective professional practice, there is a need for governmental changes and professional recognition through autonomy, respect and exclusivity in the Service of Hospital Infection Control, as well as improvements regarding information, the care provided to the patient and professional secret. The predominance of bureaucratic activities and team work were mentioned by the clinical nurses as differentiating factors of the activities performed by nurses that are members of the Commission

Rat cultured neuronal and glial cells respond differently to toxicity of unconjugated bilirubin

High levels of unconjugated bilirubin (UCB) can be neurotoxic. Nevertheless, the mechanism of UCB interaction with neural cells is still unknown. This study investigates whether cultured rat neurons and astrocytes respond differently to UCB exposure. UC