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

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

The role of minocycline in cognitive impairment and dysfunction of the blood brain barrier in experimental pneumococcal meningitis

Artigo submetido ao Curso de Medicina da UNESC como requisito parcial para obtenção do Título de Bacharel em Medicina.Bacterial meningitis is a life threatening infection associated with cognitive impairment in many survivors. The pathogen invades the CNS by penetrating through the luminal side of the cerebral endothelium, which is an integral part of the BBB. Microglia are the resident macrophages of the CNS which can trigger a host of immunological pathways. The inflammatory response from microglial activation can facilitate the elimination of invasive microorganisms; however, excessive or extended microglial activation can result in neuronal damage and eventually cell death. The inhibition of microglia using minocycline can be a relevant pharmacological tool to study the role of microglia in different CNS diseases. In this study, animals received either artificial cerebrospinal fluid or a Streptococcus pneumoniae suspension. The animals receive minocycline or saline immediately after induction. For the evaluation of the BBB integrity, the animals were killed at 12, 18 and 24 h after induction. For the behavioural tests, ten days after meningitis was induced, were subjected to open-field habituation and the step-down inhibitory task. In both cerebral structures the use of the minocycline prevented BBB disruption. In the behavioural tests the use of minocycline prevented habituation and aversive memory impairment in the meningitis/minocycline group when compared with meningitis/saline. Our results demonstrate that the minocycline was able to decrease long-term cognitive impairment and BBB dysfunction in rats survivors of meningitis representing a new pharmacological approach towards pneumococcal meningitis

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

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 10μL 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

Detection of the BRAF(V600E) Mutation in Fine Needle Aspiration Cytology of Thyroid Papillary Microcarcinoma Cells Selected by Manual Macrodissection: An Easy Tool to Improve the Preoperative Diagnosis.

Background: Papillary carcinomas with diameters that are less than or equal to 1 cm (thyroid papillary microcarcinoma [mPTC]) are quite common but can carry more risk than previously thought. The proper treatment and management of these lesions is still being debated. Even though fine needle aspiration cytology (FNAC) is considered the best method for the diagnosis of thyroid nodules, its efficacy is still questioned for mPTC. We investigated the role of BRAF gene status in preoperative cytological samples, using manual macrodissection as an additional tool to improve the diagnostic accuracy of mPTC. Methods: DNA was extracted directly from stained FNAC smears of 95 patients including 85 with histological diagnoses of papillary thyroid carcinoma (PTC) ≤1 cm and 10 with goiters. The cytological diagnoses of the 95 cases included the following: 42 samples were suspicious for papillary carcinoma, 38 were PTCs, and 15 were indeterminate lesions. DNA was then extracted from the FNAC slides after performing a "manual macrodissection" procedure. The BRAF(V600E) mutational status was determined by sequence analysis in all the patients. Results: In this study, we showed that the BRAF(V600E) mutation was present with a high frequency in patients with mPTC (74%). The presence of the mutation was independent of the size of the tumor. In our study, the combination of the cytological diagnosis and the molecular analysis was able to identify 82% of all cases of mPTC, with an increase of 37% compared with a morphological diagnosis alone. The morpho-molecular analysis was able to reduce the number of suspicious cases by >70%. All of the goiters had a wild-type BRAF status. Conclusions: The analysis of BRAF mutational status in FNAC obtained from papillary microcarcinomas demonstrates that molecular pathology, combined with morphology and molecular biology is a powerful tool for cytological diagnosis of mPTC. Our results also confirm the data supporting the biological relevance of PTCs with diameters that are ≤1 cm and the importance of "manual macrodissection" in the molecular analysis of cytological material

Detecting somaclonal variation during micropropagation of vine rootstocks using SSR molecular marker and flow cytometery analysis.

Resumo

Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases.ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. (C) 2012 Elsevier Inc. All rights reserved

Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day). The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction

Test de puntaje compuesto para la elección del tratamiento de deshidratación osmótica adecuado en muestras de anco

El test de puntaje compuesto es un test de respuesta objetiva que permite realizar una evaluación comparativa de las muestras en estudio. El puntaje se establece para cada variable o característica de acuerdo a su grado de importancia y la muestra perfecta debería tener un puntaje de 100 puntos. El objetivo de este trabajo fue aplicar el método de puntaje compuesto para elegir desde el punto de vista subjetivo el tratamiento de deshidratación osmótica (DO) adecuado en muestras de anco mínimamente procesadas. Para ello, se cortaron cubos de anco (Cucurbita moschata) de 1.0 cm de lado y se colocaron en 4 soluciones osmodeshidratantes durante 3 horas: 1) sacarosa 55°Bx, 2) sacarosa 55°Bx- 2% NaCl, 3) sacarosa 55°Bx-2% Lactato de calcio y 4) sacarosa 55°Bx-2% NaCL-2% Lactato de calcio. Las muestras fueron envasadas y almacenadas durante 7 y 10 días a 4º C, incluida la muestra testigo 0 (sin tratamiento de DO). Posteriormente se realizó el análisis sensorial con ocho panelistas semientrenados, incluyendo apariencia, olor, sabor y textura. La apariencia se ponderó con un 40%, de lo cuál se evaluó conservación de forma, color y exudado con 10, 10 y 20% respectivamente. El atributo olor representó el 30%, del cuál se evaluó olor típico (10%) y olor a fermentado (20%). Finalmente, el aspecto sabor (20%) y textura bucal (10%) sumaron el 100% del análisis sensorial del producto. Los atributos se expresaron numéricamente en una escala de 1 a 5, donde los valores extremos corresponden al mejor y peor valor del atributo respectivamente, por lo tanto el valor 100 corresponde a la mejor y 500 a la peor muestra. Luego de 7 días de almacenamiento, se obtuvieron los valores 150, 160, 250, 280 y 310 para las muestras 1, 0, 2, 4 y 3 respectivamente; y al cabo de 10 días de almacenamiento se obtuvieron los valores 180, 210, 270, 350 y 380 para las muestras 0, 1, 2, 3 y 4 respectivamente De este análisis sensorial se concluye que el tratamiento 1 resulta ser el más adecuado sensorialmente, tanto a los 7 como 10 días, teniendo en cuenta que si bien se evaluó la muestra sin tratamiento, el objetivo es aplicar la DO como método de conservación. Finalmente, es necesario complementar este resultado con un análisis microbiológico para estimar su vida útil y en consecuencia el tratamiento adecuado.Centro de Investigación y Desarrollo en Criotecnología de Alimento

Avaliação microbiológica e físico-química de açúcares mascavo comerciais.

Este trabalho teve como objetivos analisar parâmetros microbiológicos e físico-químicos de 31 marcas de açúcares mascavos. Foram realizadas as análises microbiológicas (bactérias mesófi las totais, bolores e leveduras, coliformes totais, Escherichia coli e Salmonella) e físico-químicas (polarização, umidade, cinzas condutimétricas, cor ICUMSA, açúcar redutor, açúcar redutor total e pH). Os resultados microbiológicos indicaram que houve resultados acima do limite do of ?National Food Canners and Processors? apenas para bactérias mesófi las totais. A legislação brasileira estabelece o teor mínimo de 90oS para sacarose como único parâmetro para avaliação do açúcar mascavo, sendo que apenas sete amostras atendiam ao padrão. Os resultados de umidade variaram de 2,13 a 6,02% para cinzas; de 1,15 a 3,45%;açúcares redutores; de 1,17 a 8,51%, redutores totais de 68,90 a 98,21%; pH de 5,24 a 7,8 e cor ICUMSA de 174,6 a 574,5 U.I indicando que os açúcares mascavos comercializados no Brasil não possuem padrão de produção, armazenamento e qualidade fi nal, indicado pelas diferenças dos parâmetros avaliados

Emissions of primary aerosol and precursor gases in the year 2000 and 1750 prescribed data-sets for AeroCom.

Inventories for global aerosol and aerosol precursor emissions have been collected (based on published inventories and published simulations), assessed and prepared for the year 2000 (present-day conditions) and for the year 1750 (pre-industrial conditions). These global datasets establish a comprehensive source for emission input to global modeling, when simulating the aerosol impact on climate with state-of-the-art aerosol component modules. As these modules stratify aerosol into dust, sea-salt, sulfate, organic matter and soot, for all these aerosol types global fields on emission strength and recommendations for injection altitude and particulate size are provided. Temporal resolution varies between daily (dust and sea-salt), monthly (wild-land fires) and annual (all other emissions). These datasets benchmark aerosol emissions according to the knowledge in the year 2004. They are intended to serve as systematic constraints in sensitivity studies of the AeroCom initiative, which seeks to quantify (actual) uncertainties in aerosol global modeling