296 research outputs found

    Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review

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    A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes

    Clinical Evidence of Human Pathogens Implicated in Alzheimer’s Disease Pathology and the Therapeutic Efficacy of Antimicrobials: An Overview

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    A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer\u27s disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiome has also been proposed as a modulator of AD. In this review, we focus on human-based evidence demonstrating the elevated abundance of microbes and microbe-derived molecules in AD hosts as well as their interactions with AD hallmarks. Further, the direct-purpose and potential off-target effects underpinning the efficacy of anti-microbial treatments in AD are also addressed

    A Compact Solid State Detector for Small Angle Particle Tracking

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    MIDAS (MIcrostrip Detector Array System) is a compact silicon tracking telescope for charged particles emitted at small angles in intermediate energy photonuclear reactions. It was realized to increase the angular acceptance of the DAPHNE detector and used in an experimental program to check the Gerasimov-Drell-Hearn sum rule at the Mainz electron microtron, MAMI. MIDAS provides a trigger for charged hadrons, p/pi identification and particle tracking in the region 7 deg < theta < 16 deg. In this paper we present the main characteristics of MIDAS and its measured performances.Comment: 13 pages (9 figures). Submitted to NIM

    Dysfunctional Glymphatic System with Disrupted Aquaporin 4 Expression Pattern on Astrocytes Causes Bacterial Product Accumulation in the CSF during Pneumococcal Meningitis

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    Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel\u27s functionality

    Evaluation of the brain-derived neurotrophic factor, nerve growth factor and memory in adult rats survivors of the neonatal meningitis by Streptococcus agalactiae

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    AbstractStreptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10ÎŒL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×106cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis

    Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

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    Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10 mu l of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10 mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-alpha level in frontal cortex. Prolonged treatment with canabidiol, 10 mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel. (C) 2012 Elsevier B.V. All rights reserved.CNPqFAPEMIGFAPESCUNESCNENASC project (PRONEX program CNPq/FAPESC)INCT-TMResearch Support Center on Applied Neuroscience (NAPNA-USP) [2011.1.9333.1.3]L'Oreal-UNESCO Brazil Fellowship for Women in Scienc

    ISSUES IN REFORMING TARIFF-RATE IMPORT QUOTAS IN THE AGREEMENT ON AGRICULTURE IN THE WTO

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    Contents: The Economics of Tariff Rate Quotas and the Effects of Trade Liberalization; TRQs and GATT Rules; An Overview of Tariffs, Quotas and Imports Worldwide; TRQs in the European Union; U.S. TRQs for Sugar, Tobacco and Peanuts; Dairy TRQs in the United States; Tariff Rate Quota Implementation and Administration by Developing Countries; Management of Tariff Rate Quotas in Korea and Japan; Tariff Rate Quota Administration in Canadian Agriculture; The Case of Australia and New Zealand Facing TRQs; The 1999 WTO Panel Report on the EU's Common Market Organization for Bananas; AssessmentInternational Relations/Trade,

    Efeitos de fungos termĂłfilos sobre a madeira de Eucalyptus saligna: III. a população fĂșngica.

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    Este Ă© um trabalho complementar a uma sĂ©rie de estudos com fungos termĂłfilos, em madeira de eucalipto. Seu objetivo foi determinar a ação de uma população de fungos termĂłfilos sobre a madeira e a celulose, obtida com cavacos de madeira de Eucalyptus saligna. Amostras de cavacos secos ao ar foram esterilizados por autoclavagem. ApĂłs a inoculação, os cavacos foram incubados, por 30 dias, a 30, 40 e 50oC. O inĂłculo foi preparado com uma amostra de 20 g de cavacos naturalmente contaminados com os fungos: Aspergillus sp., Dactylomyces thermophilus, Penicillium bacillisporum, Rhizomucor sp., Sporotrichum sp. e Thermoascus aurantiacus. Os cavacos foram analisados quanto aos teores de holocelulose, lignina e extrativos. Preparou-se, tambĂ©m, celulose nĂŁo branqueada com os cavacos dos tratamentos e analisou-se o rendimento bruto da celulose. A anĂĄlise dos resultados mostrou que os teores de holocelulose e lignina permaneceram inalterados revelando que os fungos nĂŁo degradam celulose ou lignina. A diminuição nos teores de extrativos começaram a ser detectados a 40 e 50oC, exceção feita aos açĂșcares livres em etanol. O maior decrĂ©scimo ocorreu a 50oC. O decrĂ©scimo no teor foi observado na fração solĂșvel em etanol-tolueno (19,3%), em diclorometano (7,1%) e em ĂĄgua quente (4%); com extrativos totais e açĂșcares livres em etanol, o decrĂ©scimo foi de 8,6% e 4,8%, respectivamente. A anĂĄlise da produção de celulose nĂŁo branqueada verificou-se uma relação direta entre produção e a temperatura de incubação. Cavacos nĂŁo inoculados e os inoculados/incubados a 30oC produziram 50,8% de celulose, enquanto que os incubados a 40 e 50oC produziram 52 e 53,1%, respectivamente
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