Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Year in review in Intensive Care Medicine 2012. II: Pneumonia and infection, sepsis, coagulation, hemodynamics, cardiovascular and microcirculation, critical care organization, imaging, ethics and legal issues.

Journal ArticleSCOPUS: re.jSCOPUS: re.jinfo:eu-repo/semantics/publishe

New materials and devices for preventing catheter-related infections

Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies

The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a Multicenter, Multinational, 14-Day Inception Cohort Study

PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients

Failure of available scoring systems to predict ongoing infection in patients with abdominal sepsis after their initial emergency laparotomy

<p>Abstract</p> <p>Background</p> <p>To examine commonly used scoring systems, designed to predict overall outcome in critically ill patients, for their ability to select patients with an abdominal sepsis that have ongoing infection needing relaparotomy.</p> <p>Methods</p> <p>Data from a RCT comparing two surgical strategies was used. The study population consisted of 221 patients at risk for ongoing abdominal infection. The following scoring systems were evaluated with logistic regression analysis for their ability to select patients requiring a relaparotomy: APACHE-II score, SAPS-II, Mannheim Peritonitis Index (MPI), MODS, SOFA score, and the acute part of the APACHE-II score (APS).</p> <p>Results</p> <p>The proportion of patients requiring a relaparotomy was 32% (71/221). Only 2 scores had a discriminatory ability in identifying patients with ongoing infection needing relaparotomy above chance: the APS on day 1 (AUC 0.61; 95%CI 0.52-0.69) and the SOFA score on day 2 (AUC 0.60; 95%CI 0.52-0.69). However, to correctly identify 90% of all patients needing a relaparotomy would require such a low cut-off value that around 80% of all patients identified by these scoring systems would have negative findings at relaparotomy.</p> <p>Conclusions</p> <p>None of the widely-used scoring systems to predict overall outcome in critically ill patients are of clinical value for the identification of patients with ongoing infection needing relaparotomy. There is a need to develop more specific tools to assist physicians in their daily monitoring and selection of these patients after the initial emergency laparotomy.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN 51729393">ISRCTN 51729393</a></p

Patient Destination after Discharge from Intensive Care Units: Wards or Intermediate Care Units?

This study characterizes patients hospitalized in Intensive Care Units (ICUs) of hospitals that have intermediate units (IU) regarding their demographic and clinical data and identifies factors related to discharge from these units. This prospective longitudinal study involved 600 adult patients hospitalized in general ICUs in four hospitals in São Paulo, SP, Brazil. Demographic and clinical characteristics were similar to those found in other studies addressing patients hospitalized in ICUs. Factors associated with discharge from ICU to IU were: age &#8805;60 years, diseases related to the nervous, circulatory or respiratory systems, originated from the IU, and Simplified Acute Physiologic Score II (SAPS II), Logistic Organ Dysfunction (LODS) and Nursing Activities Scores (NAS) at admission and discharge from the ICU. Age and risk of death at admission in the ICU, according to SAPS II, stood out as indicators of discharge to IUs in the Multiple Logistic Regression analysis.Este estudio tuvo como objetivos caracterizar a los pacientes internados en unidades de terapia intensiva (UTI) de hospitales con unidades intermediarias - en lo que se refiere a los datos demográficos y clínicos - e identificar los factores relacionados con el alta médica para esa unidad. Es estudio prospectivo longitudinal, con 600 pacientes adultos, internados en UTIs generales de cuatro hospitales del municipio de Sao Paulo. En los resultados, las características demográficas y clínicas fueron similares a las descritas en otros estudios sobre pacientes en UTIs. Los factores asociados con el alta hospitalaria para la unidad intermediaria fueron: edad &#8805;60 años, antecedentes relacionados al sistema nervioso, circulatorio o respiratorio, procedencia de la unidad intermediaria y valores del Simplified Acute Physiologic Score II (SAPS II), Logistic Organ Dysfunction (LODS) y Nursing Activities Score (NAS) en la admisión y el alta de la UTI. En el análisis de regresión logística múltiple la edad y el riesgo de muerte en la admisión, por el SAPS II, se destacaron como indicadores del alta médica para la unidad intermediaria.Este estudo teve como objetivos caracterizar os pacientes internados em unidade de terapia intensiva (UTI) de hospitais com unidades intermediárias, quanto aos dados demográficos e clínicos, e identificar os fatores relacionados à alta para essa unidade. É estudo prospectivo longitudinal, com 600 pacientes adultos, internados em UTIs gerais de quatro hospitais do município de São Paulo. Nos resultados, as características demográficas e clínicas foram similares às descritas em outros estudos sobre pacientes em UTIs. Os fatores associados à alta para unidade intermediária foram: idade &#8805;60 anos, antecedentes relacionados ao sistema nervoso, circulatório ou respiratório, procedência da unidade intermediária e valores do Simplified Acute Physiologic Score II (SAPS II), Logistic Organ Dysfunction (LODS) e Nursing Activities Score (NAS) na admissão e alta da UTI. Na análise de regressão logística múltipla a idade e o risco de morte na admissão, pelo SAPS II, destacaram-se como indicadores de alta para unidade intermediária