Efficient and accurate experimental design for enzyme kinetics: Bayesian studies reveal a systematic approach

In areas such as drug development, clinical diagnosis and biotechnology research, acquiring details about the kinetic parameters of enzymes is crucial. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. We demonstrate that a Bayesian approach (the use of prior knowledge) can produce major gains quantifiable in terms of information, productivity and accuracy of each experiment. Developing the use of Bayesian Utility functions, we have used a systematic method to identify the optimum experimental designs for a number of kinetic model data sets. This has enabled the identification of trends between kinetic model types, sets of design rules and the key conclusion that such designs should be based on some prior knowledge of K-M and/or the kinetic model. We suggest an optimal and iterative method for selecting features of the design such as the substrate range, number of measurements and choice of intermediate points. The final design collects data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. (C) 2003 Elsevier Science B.V. All rights reserved.

Experimental evidence for a partially dissociated water bilayer on Ru{0001}

Core-level photoelectron spectra, in excellent agreement with ab initio calculations, confirm that the stable wetting layer of water on Ru{0001} contains O-H and H2O in roughly 3:5 proportion, for OHx coverages between 0.25 and 0.7 ML, and T<170 K. Proton disorder explains why the wetting structure looks to low energy electron diffraction (LEED) to be an ordered p(root3xroot3)R30degrees adlayer, even though approximate to3/8 of its molecules are dissociated. Complete dissociation to atomic oxygen starts near 190 K. Low photon flux in the synchrotron experiments ensured that the diagnosis of the nature of the wetting structure quantified by LEED is free of beam-induced damage.

The effects of flavonoid and other polyphenol consumption on cognitive performance: A systematic research review of human experimental and epidemiological studies

Literature reviews suggest flavonoids, a sub-class of polyphenols, are beneficial for cognition. This is the first review examining the effect of consumption of all polyphenol groups on cognitive function. Inclusion criteria were polyphenol vs. control interventions and epidemiological studies with an objective measure of cognitive function. Participants were healthy or mildly cognitively impaired adults. Studies were excluded if clinical assessment or diagnosis of Alzheimer’s disease, dementia, or cognitive impairment was the sole measure of cognitive function, or if the polyphenol was present with potentially confounding compounds such as caffeine (e.g. tea studies) or Ginkgo Biloba. 28 studies were identified; 4 berry juice studies, 4 cocoa studies, 13 isoflavone supplement studies, 3 other supplement studies, and 4 epidemiological surveys. Overall, 16 studies reported cognitive benefits following polyphenol consumption. Evidence suggests that consuming additional polyphenols in the diet can lead to cognitive benefits, however, the observed effects were small. Declarative memory and particularly spatial memory appear most sensitive to polyphenol consumption and effects may differ depending on polyphenol source. Polyphenol berry fruit juice consumption was most beneficial for immediate verbal memory, whereas isoflavone based interventions were associated with significant improvements for delayed spatial memory and executive function. Comparison between studies was hampered by methodological inconsistencies. Hence, there was no clear evidence for an association between cognitive outcomes and polyphenol dose response, duration of intervention, or population studied. In conclusion, however, the findings do imply that polyphenol consumption has potential to benefit cognition both acutely and chronically.

Mobile sink based fault diagnosis scheme for wireless sensor networks

Network diagnosis in Wireless Sensor Networks (WSNs) is a difficult task due to their improvisational nature, invisibility of internal running status, and particularly since the network structure can frequently change due to link failure. To solve this problem, we propose a Mobile Sink (MS) based distributed fault diagnosis algorithm for WSNs. An MS, or mobile fault detector is usually a mobile robot or vehicle equipped with a wireless transceiver that performs the task of a mobile base station while also diagnosing the hardware and software status of deployed network sensors. Our MS mobile fault detector moves through the network area polling each static sensor node to diagnose the hardware and software status of nearby sensor nodes using only single hop communication. Therefore, the fault detection accuracy and functionality of the network is significantly increased. In order to maintain an excellent Quality of Service (QoS), we employ an optimal fault diagnosis tour planning algorithm. In addition to saving energy and time, the tour planning algorithm excludes faulty sensor nodes from the next diagnosis tour. We demonstrate the effectiveness of the proposed algorithms through simulation and real life experimental results.

O exame direto do lavado broncoalveolar para o diagnóstico precoce de pneumonia nosocomial : um modelo experimental em ratos

A pneumonia nosocomial é a principal causa de infecção nosocomial em unidades de tratamento intensivo e possui alta morbi/mortalidade. A incidência cumulativa varia, conforme os autores, entre limites amplos desde 8% até 51%, dependendo do tipo de paciente e do uso de instrumentação das vias respiratórias. Nos casos específicos das pneumonias de má resolução e da pneumonia associada à ventilação mecânica, o diagnóstico é problemático devido à ausência de uma padronização definitiva, decorrente não só da grande variabilidade fisiopatológica como também da pouca acurácia dos critérios clínicos, microbiológicos e radiológicos. Estes fatos ensejaram a utilização progressiva de técnicas invasivas sofisticadas para coleta de amostras respiratórias endobrônquicas. Entretanto, a validação dessas técnicas para uso sistemático depende ainda de estudos que avaliem não só o seu custo/benefício em cenários clínicos diversos como também a comparação de seu desempenho para o diagnóstico com um padrão-ouro histopatológico. Além disso, o rendimento das técnicas invasivas é freqüentemente limitado quando são aplicadas em pacientes sob antibioticoterapia, que constituem a maioria dos casos em unidades de cuidados intensivos. A otimização desses testes, discutindo suas indicações e avaliando sua capacidade técnica para a confirmação ou exclusão de pneumonia, é justificada pela necessidade da instituição precoce e correta do tratamento, pois disto resulta menor mortalidade, redução de custos e permanência no hospital. Entre os testes que podem auxiliar no diagnóstico encontra-se o exame direto do lavado broncoalveolar, que proporciona resultados precoces e úteis para a tomada de decisão, mas não suficientemente testados em diferentes situações clínicas ou experimentais. Com o objetivo de avaliar o rendimento diagnóstico do exame direto precoce e das culturas quantitativas obtido por lavado broncoalveolar, estudou-se sua utilização em um modelo experimental de pneumonia provocada através de inoculação bacteriana intrabrônquica em ratos. O estudo comparou a acurácia do exame direto e dos exames culturais em três grupos de animais: Grupo A com pneumonia pneumocócica (37 animais); Grupo P com pneumonia por P. aeruginosa (26 animais) e Grupo B controle (10 animais), utilizando a histopatologia dos pulmões como teste de referência para o diagnóstico. Os Grupos A e P foram ainda randomizados em dois subgrupos cada, para tratamento ou não com antibióticos, usando penicilina no grupo pneumococo e amicacina no grupo Pseudomonas. Como resultado, observou-se que nos animais com pneumonia e ausência de antibióticos a pesquisa de bactéria fagocitada (BIC) no exame direto mostrou um rendimento elevado para o diagnóstico, sendo superior ao das culturas quantitativas. No grupo com pneumonia pneumocócica a BIC mostrou: S:94,4% a 100%, E:100%, VPP:100% e VPN:100%; e as culturas quantitativas mostraram: S:77,8%, E:100%, VPP:100%, VPN:40%. Nos com pneumonia por Pseudomonas a BIC obteve: S: 69%, E:100%; VPP:100% e VPN:71,4%); e as culturas quantitativas mostraram valores muito baixos: S:28,6%, E:100%, VPP:100% e VPN:50%). Nos animais com pneumonia pneumocócica sob tratamento antibiótico havia uma queda acentuada de sensibilidade das culturas quantitativas (S:21%) e, em menor grau da BIC (S:57,9%), mas sem perda da especificidade de ambos os exames. Ao contrário, nos animais com pneumonias por Pseudomonas sob tratamento não havia alteração no rendimento dos dois exames, cujos resultados foram semelhantes aos dos animais sem tratamento. Não havia diferenças de leitura da BIC para o diagnóstico, contando a sua positividade em macrófagos ou em neutrófilos infectados. A avaliação global dos casos estudados, reunindo todos os grupos (tratados e não-tratados) em ambos os modelos de pneumonia, mostrou que a acurácia do exame direto, representado pela pesquisa da BIC, foi superior (66%) ao das culturas quantitativas (53%). As conclusões principais do estudo foram: 1) o exame direto do lavado broncoalveolar (LBA) mostrou-se um teste útil e de alto rendimento para o diagnóstico de pneumonia quando realizado na ausência de antibióticos; 2) o LBA feito na vigência de antibióticos efetivos para a pneumonia perde mais de 50% de sua acurácia, mas não é afetado quando o antibiótico for ineficaz ou houver resistência ao mesmo; 3) a pesquisa de BIC no LBA é um exame de resultado precoce, de alta especificidade e com melhor rendimento do que as culturas quantitativas.

Abordagem inicial de lesões mamárias por biopsia helicóide: estudo experimental

OBJECTIVE: Evaluating the kit-Bh performance in carrying out of breast biopsies. METHODS: They were randomly selected a sample of 30 patients with breast cancer undergoing mastectomy, based on the results of a pilot study from February 2008 to April 2010. They were excluded women with had not palpable, stone-hard consistency tumors, previous surgical manipulation or that contains liquid. Using the helicoid biopsy Kit (kit Bh) and an equipment Core biopsy with cannula and needle and 14 gauge respectively, it was collected a fragment of sound equipment in the area and in tumors in each specimen, totaling 120 fragments for histological study. For data analysis, it was defined a 95% confidence level and used the SPSS-13 version, the Kappa index and the parametric Student t test. RESULTS: Mean age of patients was 51.6 years (± 11.1 years). The infiltrating ductal carcinoma showed a higher incidence, 26 cases (86.7%). The Core biopsy had a sensitivity of 93.3%, specificity of 100% and accuracy 96.7%, while the helicoid biopsy had a sensitivity of 96.7%, specificity of 100% and accuracy 98.3%. By comparing the histology of tumors and the fragments of biopsies, there was high degree of agreement in diagnoses (kappa of 0.93 with p <0.05) CONCLUSION: Both devices provided the histological diagnosis of lesions with high accuracy. Results of this study showed that the helicoid biopsy is a reliable alternative in 22 the preoperative diagnosis of breast lesions. Further studies in vivo better will define the role of Kit Bh in the diagnosis of these lesions

Hemogasometria de eqüinos submetidos à obstrução experimental do duodeno, íleo e cólon maior

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Características celulares e bioquímicas do líquido peritoneal de equinos submetidos à obstrução experimental do duodeno, íleo e cólon maior

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental Ehrlichia canis infection changes acute-phase proteins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dermatophyte-host relationship of a murine model of experimental invasive dermatophytosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Accuracy of Tc-99m-sestamibi scintimammography for breast cancer diagnosis

Scintimammography using Tc-99m-sestamibi is a noninvasive and painless diagnostic imaging method that is used to detect breast cancer when mammography is inconclusive Because of the advantages of labeling v '7,ith Tc-99m-sestamibi and its high efficiency in detecting carcinomas, it is the most widespread agent for this purpose Its accumulation in the tumor has multifactorial causes and does not depend on the presence of architectural distortion or local or diffuse density variation in the breast The objective of tfiis study was to evaluate the accuracy of scintimammography 1 for detecting breast cancer One hundred and fifty-seven patients presenting 158 palpable and non-palpable breast nodules were evaluated Three patients were male and 154 were female, aged between 14 and 81 years All patients underwent scintimammography, and the nodule was subjected i to cytological or histological study, i e, the gold standard for diagnosing cancer One hundred and eleven malignant and 47 benign nodules were detected, with predominance of ductal carcinomas (n=94) and fibroadenoma/fibrocysiic condition (n=11/n=11), respectively The mean size was 3 11 cm (7-10 cm) among the malignant nodules and 2 07 cm among the benign nodules (0 5-10 cm) The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 89, 89, 95, 78 and 89%, respectively Analysis on the histological types showed that the technique was more effective on tumors that were more aggressive, such as ductal carcinoma In this study, Tc-99m-sestamibi scintim immography was shown to be an important tool for diagnosing breast cancer when mammography was inconclusive

Hematological and biochemical profiles and histopathological evaluation of experimental intoxication by sodium fluoroacetate in cats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Trombectomia com cateter de Fogarty no tratamento da tromboflebite jugular experimental em eqüinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Taenia saginata: Differential diagnosis of human taeniasis by polymerase chain reaction-restriction fragment length polymorphism assay

Speciation of Taenia in human stool is important because of their different clinical and epidemiological features. DNA analysis has recently become possible which overcomes the problems of differentiating human taeniid cestodes morphologically. In the present study, we evaluated PCR coupled to restriction fragment length polymorphism to differentiate Taenia solium from Taenia saginata eggs present in fecal samples from naturally infected patients. A different Dral-RFLP pattern: a two-band pattern (421 and 100 bp) for T saginata and a three-band pattern (234, 188, and 99 bp) for T solium was observed allowing the two species to be separated.. The lower detection limit of the PCR-RFLP using a non-infected fecal sample prepared with a given number of T saginata eggs was 34 eggs in 2 g stool sediment. The 521 bp mtDNA fragment was detected in 8 out of 12 Taenia sp. carriers (66.6%). of these, three showed a T solium pattern and five a T saginata pattern. (c) 2005 Elsevier B.V. All rights reserved.

Taenia saginata: polymerase chain reaction for taeniasis diagnosis in human fecal samples

The taeniasis-cysticercosis complex is a zoonosis of great medical and economic importance where humans play an important role as the carrier of adult stage of Taenia solium and Taenia saginata. This paper describes PCR standardization that can be applied in human fecal samples for taeniasis diagnosis. DNA extraction was achieved with DNAzol reagent, after egg disruption with glass beads. DNA prepared from fecal specimens was first purified and PCR amplified generating fragments of 170 and 600 bp. The assay described herein provides an important tool for T saginata identification in human fecal samples. (C) 2003 Elsevier B.V. (USA). All rights reserved.