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1.
Clin Dev Immunol ; 2013: 132432, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348673

RESUMO

The expression of chemokines (CCL-2 and CXCL-8) and cytokines (IL-1 α , IL-1 ß , IL-6, TNF- α , and IL-10) was evaluated by RT-qPCR in colostrum-deprived pigs vaccinated and challenged with Haemophilus parasuis serovar 5. Two vaccines containing native proteins with affinity to porcine transferrin (NPAPTim and NPAPTit) were tested, along with two control groups: one inoculated with PBS instead of antigen (challenge group (CHG)), and another one nonimmunized and noninfected (blank group). The use of NPAPTim and NPAPTit resulted in complete protection against H. parasuis (no clinical signs and/or lesions), and both vaccines were capable of avoiding the expression of the proinflammatory molecules to levels similar to physiological values in blank group. However, overexpression of all proinflammatory molecules was observed in CHG group, mainly in the target infection tissues (brain, lungs, and spleen). High expression of CCL-2, CXCL-8, IL-1 α , IL-1 ß , and IL-6 can be considered one of the characteristics of H. parasuis infection by serovar 5.


Assuntos
Vacinas Bacterianas/imunologia , Quimiocinas/genética , Citocinas/genética , Infecções por Haemophilus/veterinária , Haemophilus parasuis/imunologia , Doenças dos Suínos/prevenção & controle , Transferrina/imunologia , Animais , Vacinas Bacterianas/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Expressão Gênica , Infecções por Haemophilus/prevenção & controle , Humanos , Mediadores da Inflamação/metabolismo , Suínos , Doenças dos Suínos/metabolismo , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/metabolismo
2.
Cancer Radiother ; 25(8): 790-794, 2021 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33390319

RESUMO

Image-guided radiotherapy (IGRT) has become a standard irradiation technique to improve the clinical outcome of patients in terms of toxicity and local control due to better targeting of radiation during the irradiation fraction. Positioning imaging systems, whether embedded or not, such as kV for 2×2D acquisitions and especially kVCBCT for 3D acquisitions are however irradiating in a large volume including the target volume but also healthy tissue, with a theoretical risk of increased toxicity and second cancer. It therefore appears very important both to optimize the absorbed dose due to IGRT practice but also to report it, especially in case of kVCBCT. The AAPM report published in 2018 (« Image guidance doses delivered during radiotherapy: Quantification, management, and reduction ¼) proposes a management of image guidance doses delivered during radiotherapy. This report is the basis of this focus article that aims at giving orders of magnitude and proposing a management of image guidance doses delivered during radiotherapy in clinical practice. The dose delivered per kVCBCT is about 0.5 to 2 cGy at isocenter according to treatment site. As long as the calculation algorithms are not available in the treatment planning systems, it seems appropriate to use at least the published dose orders of magnitude. This estimate should ultimately allow the clinician to decide on the therapeutic strategy in the event of accumulation of positioning imaging sessions.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Órgãos em Risco/efeitos da radiação , Radioterapia Guiada por Imagem/métodos , Humanos , Método de Monte Carlo , Posicionamento do Paciente , Doses de Radiação , Radioterapia Guiada por Imagem/instrumentação , Terminologia como Assunto
3.
J Appl Microbiol ; 109(3): 863-72, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20337766

RESUMO

AIMS: To develop a novel molecular tool for the quantitative detection of the ruminant pathogen Listeria ivanovii in different biological matrices. METHODS AND RESULTS: A real-time PCR (RTi-PCR) for the quantitative and species-specific identification of L. ivanovii was designed to target the region of the smcL gene. The assay includes an internal amplification control (IAC) to avoid false-negative results. The smcL-IAC RTi-PCR assay was 100% selective and allowed the detection of as little as one genome equivalent in 45% of reactions. The quantification accuracy was excellent, as demonstrated by its high linearity (R(2)>0·9989) and PCR efficiency (E>0·984) over a 6-log dynamic range, down to 10 genome equivalents. Finally, the applicability of this assay was evaluated with artificially contaminated biological matrices implicated in the transmission of this bacterium such as sheep raw milk, blood and amniotic fluid. The smcL-IAC RTi-PCR assay allowed the detection of as few as 50 colony forming unit numbers (CFUs) per 25 ml of raw milk, 43 CFUs per 1 ml of blood or 50 CFUs per 1 ml of amniotic fluid. CONCLUSIONS: This method can be an adequate alternative for the identification of L. ivanovii and for complete diagnosis of animal and human listeriosis. significance and impact of the study: We present an alternative for the detection of another pathogenic member of Listeria genus, which can help to distinguish from Listeria monocytogenes and therefore facilitates the establishment of preventive and prophylactic measures in food and farm environments.


Assuntos
Listeria/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Esfingomielina Fosfodiesterase/genética , Animais , Genes Bacterianos , Marcadores Genéticos , Humanos , Listeria/genética , Listeriose/diagnóstico , Listeriose/veterinária , Reação em Cadeia da Polimerase/veterinária , Ovinos/microbiologia
4.
Med Phys ; 47(9): 4531-4542, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32497267

RESUMO

PURPOSE: Image-guided radiotherapy (IGRT) improves tumor control but its intensive use may entrain late side effects caused by the additional imaging doses. There is a need to better quantify the additional imaging doses, so they can be integrated in the therapeutic workflow. Currently, no dedicated software enables to compute patient-specific imaging doses on a wide range of systems and protocols. As a first step toward this objective, we propose a common methodology to model four different kV-imaging systems used in radiotherapy (Varian's OBI, Elekta's XVI, Brainlab's ExacTrac, and Accuray's Cyberknife) using a new type of virtual source model based on Monte Carlo calculations. METHODS: We first describe our method to build a simplified description of the photon output, or virtual source models (VSMs), of each imaging system. Instead of being constructed using measurement data, as it is most commonly the case, our VSM is used as the summary of the phase-space files (PSFs) resulting from a first Monte Carlo simulation of the considered x-ray tube. Second, the VSM is used as a photon generator for a second MC simulation in which we compute the dose. Then, the proposed VSM is thoroughly validated against standard MC simulation using PSFs on the XVI system. Last, each modeled system is compared to profiles and depth-dose-curve measurements performed in homogeneous phantom. RESULTS: Comparisons between PSF-based and VSM-based calculations highlight that VSMs could provide equivalent dose results (within 1% of difference) than PSFs inside the imaging field-of-view (FOV). In contrast, VSMs tend to underestimate (for up to 20%) calculated doses outside of the imaging FOV due to the assumptions underlying the VSM construction. In addition, we showed that the use of VSMs allows reducing calculation time by at least a factor of 2.8. Indeed, for identical simulation times, statistical uncertainties on dose distributions computed using VSMs were much lower than those obtained from PSF-based calculations. CONCLUSIONS: For each of the four imaging systems, VSMs were successfully validated against measurements in homogeneous phantoms, and are therefore ready to be used for future preclinical studies in heterogeneous or anthropomorphic phantoms. The cross system modeling methodology developed here should enable, later on, to estimate precisely and accurately patient-specific 3D dose maps delivered during a large range of kV-imaging procedures.


Assuntos
Radioterapia Guiada por Imagem , Simulação por Computador , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
5.
Int J Microbiol ; 2020: 8253546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322275

RESUMO

Evaluation of resistance to antituberculosis drugs is routinely performed with genotypic or phenotypic methods; however, discordance can be seen between these different methodologies. Our objective was to identify mutations that could explain discordant results in the evaluation of susceptibility to rifampicin and isoniazid between molecular and phenotypic methods, using whole genome sequencing (WGS). Peruvian strains showing sensitive results in the GenoType MTBDRplus v2.0 test and resistant results in the proportions in the agar-plaque test for isoniazid or rifampin were selected. Discordance was confirmed by repeating both tests, and WGS was performed, using the Next Generation Sequencing methodology. Obtained sequences were aligned "through reference" (genomic mapping) using the program BWA with the algorithm "mem", using as a reference the genome of the M. tuberculosis H37Rv strain. Discordance was confirmed in 14 strains for rifampicin and 21 for isoniazid, with 1 strain in common for both antibiotics, for a total of 34 unique strains. The most frequent mutation in the rpoB gene in the discordant strains for rifampicin was V170F. The most frequent mutations in the discordant strains for isoniazid were katG R463L, kasA G269S, and Rv1592c I322V. Several other mutations are reported. This is the first study in Latin America addressing mutations present in strains with discordant results between genotypic and phenotypic methods to rifampicin and isoniazid. These mutations could be considered as future potential targets for genotypic tests for evaluation of susceptibility to these drugs.

6.
Rev Neurol ; 71(3): 99-109, 2020 Aug 01.
Artigo em Espanhol | MEDLINE | ID: mdl-32672348

RESUMO

INTRODUCTION: The 22q11 deletion syndrome (S22q11) is one of the most prevalent genetic disorders, resulting in multiple systemic and neuropsychological features. AIM: To describe the language profile in a sample of Spanish subjects with S22q11. PATIENTS AND METHODS: A sample of 30 Spanish participants with S22q11 aged between 5 years and 21 years and 11 months (mean: 12.14 ± 4.20 years) was evaluated using standardized tests and a questionnaire administered to parents. RESULTS: Almost half of the subjects obtained better results in expressive language than in comprehensive language and the majority obtained a higher score in language content than in language memory. The results suggest that people with S22q11 present language difficulties that improve with age to a certain level and subsequently stabilize. A specific profile is observed that suggests that pragmatic difficulties are a consequence of this language profile and not only of social difficulties already described in this pathology. CONCLUSIONS: In the sample of the present study, children and young people with S22q11 present specific language and pragmatic disorders. More than half of the study participants did not obtain significant differences between the level of expressive and receptive language. Most presented semantic fluency difficulties. The type and degree of impairment in pragmatic skills suggest that the basic problem may be related to their language difficulties.


TITLE: Lenguaje de niños y jóvenes con síndrome de deleción 22q11.Introducción. El síndrome de deleción 22q11 (S22q11) es uno de los trastornos genéticos más prevalentes, y presenta múltiples alteraciones sistémicas y neuropsicológicas. Objetivo. Describir el perfil de lenguaje y pragmática asociado a este síndrome. Pacientes y métodos. Se evaluó una muestra de 30 participantes españoles con S22q11 de edades comprendidas entre 5 años, y 21 años y 11 meses (media: 12,14 ± 4,2 años) mediante pruebas estandarizadas y un cuestionario administrado a los padres. Resultados. Casi la mitad de la muestra obtuvo mejores resultados en el lenguaje expresivo que en el comprensivo, y la mayoría logró una mayor puntuación en el contenido del lenguaje que en la memoria del lenguaje. Los resultados sugieren que las personas con S22q11 presentan dificultades de lenguaje que mejoran con la edad hasta cierto nivel y, posteriormente, se estabilizan. Se observa un perfil específico que sugiere que las dificultades pragmáticas son consecuencia de este perfil de lenguaje y no sólo de dificultades sociales ya descritas en esta patología. Conclusiones. En la muestra del presente estudio, los niños y jóvenes con S22q11 presentan alteraciones específicas del lenguaje y la pragmática. Más de la mitad de los participantes del estudio no obtuvieron diferencias significativas entre el nivel de lenguaje expresivo y el receptivo. La mayoría presentó dificultades de fluencia semántica. El tipo y el grado de las alteraciones que presentan en las habilidades pragmáticas sugieren que el problema básico podría estar relacionado con sus dificultades lingüísticas.


Assuntos
Síndrome da Deleção 22q11/complicações , Transtornos do Desenvolvimento da Linguagem/etiologia , Adolescente , Afasia de Broca/etiologia , Afasia de Broca/genética , Afasia de Wernicke/etiologia , Afasia de Wernicke/genética , Criança , Pré-Escolar , Escolaridade , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/genética , Testes de Linguagem , Masculino , Pais , Classe Social , Inquéritos e Questionários , Qualidade da Voz , Adulto Jovem
7.
Rev Neurol ; 68(3): 99-106, 2019 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-30687916

RESUMO

INTRODUCTION: The 22q11 deletion syndrome (S22q11) is a genetic disorder caused by the loss of a fragment of the chromosome 22. The clinical manifestations associated with the syndrome are diverse, including learning difficulties and alterations in voice, speech and language. However, to date we have not found any study that evaluates these aspects in the Spanish population with S22q11. PATIENTS AND METHODS: We evaluate the voice and speech of a sample of 10 boys and 7 girls, aged 3 years and 3 months to 13 years and 9 months old (mean age: 9,4 ± 3,5 years old) with S22q11, with voice recordings and a phonological and phonetic evaluation. Also, semistructured type interview is administered to parents. RESULTS: Most children of our series, both male and female, with S22q11 have a deeper voice than expected by gender and age, except for male children over 12 years. In terms of intensity, all of them are within the parameters of normality in spontaneous conversation. Almost all of them showed alterations in voice quality, mainly due to hypernasality. Regarding the speech, there are major difficulties in the articulation of fricatives, affricates and vibrant rhotic consonant clusters + /r/. Likewise, children, especially the youngest ones, make use of glottal stops to replace consonants. CONCLUSIONS: In the studied sample, most of the children with S22q11 have specific voice and speech alterations.


TITLE: Voz y habla de los niños con sindrome de delecion de 22q11.Introduccion. El sindrome de delecion de 22q11 (S22q11) es un trastorno genetico causado por la perdida de un fragmento del cromosoma 22. Las manifestaciones clinicas que presenta quien lo padece son diversas, incluyendo dificultades del aprendizaje y alteraciones de la voz, el habla y el lenguaje. No obstante, hasta ahora no hemos encontrado ningun estudio que evalue estos aspectos en la poblacion española con el S22q11. Pacientes y metodos. Se evalua la voz y el habla de una muestra de 10 niños y 7 niñas, de 3 años y 3 meses a 13 años y 9 meses (edad media: 9,4 ± 3,5 años), con el S22q11, a traves de registros de voz y de una prueba de evaluacion fonologica y fonetica. Ademas, se realiza una entrevista semiestructurada a los padres. Resultados. La mayoria de los niños y las niñas con el S22q11 tienen una voz mas grave de lo esperable por su sexo y edad, a excepcion de los niños varones con mas de 12 años. En cuanto a la intensidad, todos ellos se encuentran dentro de los parametros de normalidad en la conversacion espontanea. Todos presentan alteraciones del timbre, principalmente por hipernasalidad. Respecto al habla, hay mayores dificultades en la articulacion de las fricativas, las africadas, la rotica vibrante (/r/) y los grupos consonanticos + /r/. Asimismo, los niños, sobre todo los mas pequeños, utilizan las oclusivas gloticas para sustituir consonantes. Conclusiones. En la muestra estudiada, la mayoria de los niños con el S22q11 presenta alteraciones especificas tanto de la voz como del habla.


Assuntos
Síndrome da Deleção 22q11/fisiopatologia , Transtornos da Articulação/etiologia , Qualidade da Voz , Síndrome da Deleção 22q11/complicações , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/fisiopatologia , Adolescente , Transtornos da Articulação/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Palato/anormalidades
8.
Mol Oral Microbiol ; 32(6): 511-516, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28654195

RESUMO

The oral cavity harbors one of the most diverse microbiomes in the human body. It has been shown to be the second most complex in the body after the gastrointestinal tract. Upon death, the indigenous microorganisms lead to the decomposition of the carcass. Therefore, the oral cavity and gastrointestinal tract microbiomes play a key role in human decomposition. The aim of the present study is to monitor the microbiome of decaying bodies on a daily basis and to identify signature bacterial taxa, that can improve postmortem interval estimation. Three individuals (one male and two female) donated to the University of Tennessee Forensic Anthropology Center for the W.M. Bass Donated Skeletal Collection were studied. Oral swab samples were taken daily throughout the different stages of cadaveric putrefaction. DNA was extracted and analyzed by next-generation sequencing techniques. The three cadavers showed similar overall successional changes during the decomposition process. Firmicutes and Actinobacteria are the predominant phyla in the fresh stage. The presence of Tenericutes corresponds to bloat stage. Firmicutes is the predominant phylum in advanced decay, but the Firmicutes community is a different one from the predominant Firmicutes of the fresh stage. This study depicts the thanatomicrobiome successional changes in the oral cavity, and highlights its potential use in forensic cases as a quantitative and objective approach to estimate postmortem interval, from an ecological rationale.


Assuntos
Bactérias/classificação , Cadáver , Microbiota , Boca/microbiologia , Adulto , Idoso de 80 Anos ou mais , Bactérias/genética , Biodiversidade , DNA Bacteriano/análise , Descompressão , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microbiota/genética , Mudanças Depois da Morte , RNA Ribossômico 16S/genética , Fatores Sexuais
9.
Neurosci Lett ; 398(3): 201-5, 2006 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-16483718

RESUMO

Non phase-locked oscillatory changes were studied in seven healthy volunteers during two different reaction time movement paradigms, in which the stimulus was a wrist movement (either extension or flexion) performed by another person seated in front of the subject (examiner). In the first paradigm (imitation), the subject was instructed to perform the same movement observed. In the second paradigm (non-imitation), the subject was instructed to perform the opposite movement (flexion when an extension was observed, and vice-versa). Changes in the 7-37 Hz range band were determined by means of Gabor transforms. A frontal energy increase (event-related synchronization, ERS) around 15 Hz could be observed in the frontal region after the examiner's movement; this frontal ERS was significantly larger in the non-imitation paradigm. A typical alpha and beta movement-related event-related desynchronization/synchronization (ERD/ERS) pattern was also observed in both paradigms in the central region. The beta-ERD was significantly larger in the imitation paradigm. Our results show that the motor preparation mechanisms involved in an imitated and a non-imitated movement are different.


Assuntos
Mapeamento Encefálico , Eletroencefalografia , Lobo Frontal/fisiologia , Comportamento Imitativo , Movimento , Desempenho Psicomotor , Adulto , Ritmo beta , Sincronização Cortical , Feminino , Humanos , Masculino , Tempo de Reação , Punho/fisiologia
10.
Neuroimaging Clin N Am ; 26(4): 667-689, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27712799

RESUMO

Some brain tumors results are interesting due to their rarity at presentation and overwhelming imaging characteristics, posing a diagnostic challenge in the eyes of any experienced neuroradiologist. This article focuses on the most important features regarding epidemiology, location, clinical presentation, histopathology, and imaging findings of cases considered "bizarre." A review of the most recent literature dealing with these unusual tumors and pseudotumors is presented, highlighting key points related to the diagnosis, treatments, outcomes, and differential diagnosis.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neuroimagem/métodos , Pinealoma/diagnóstico por imagem , Malformações Vasculares/diagnóstico por imagem , Adulto , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Humanos , Glândula Pineal/diagnóstico por imagem
11.
Phys Med Biol ; 61(14): 5215-52, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27353090

RESUMO

This work aims at developing a generic virtual source model (VSM) preserving all existing correlations between variables stored in a Monte Carlo pre-computed phase space (PS) file, for dose calculation and high-resolution portal image prediction. The reference PS file was calculated using the PENELOPE code, after the flattening filter (FF) of an Elekta Synergy 6 MV photon beam. Each particle was represented in a mobile coordinate system by its radial position (r s ) in the PS plane, its energy (E), and its polar and azimuthal angles (φ d and θ d ), describing the particle deviation compared to its initial direction after bremsstrahlung, and the deviation orientation. Three sub-sources were created by sorting out particles according to their last interaction location (target, primary collimator or FF). For each sub-source, 4D correlated-histograms were built by storing E, r s , φ d and θ d values. Five different adaptive binning schemes were studied to construct 4D histograms of the VSMs, to ensure histogram efficient handling as well as an accurate reproduction of E, r s , φ d and θ d distribution details. The five resulting VSMs were then implemented in PENELOPE. Their accuracy was first assessed in the PS plane, by comparing E, r s , φ d and θ d distributions with those obtained from the reference PS file. Second, dose distributions computed in water, using the VSMs and the reference PS file located below the FF, and also after collimation in both water and heterogeneous phantom, were compared using a 1.5%-0 mm and a 2%-0 mm global gamma index, respectively. Finally, portal images were calculated without and with phantoms in the beam. The model was then evaluated using a 1%-0 mm global gamma index. Performance of a mono-source VSM was also investigated and led, as with the multi-source model, to excellent results when combined with an adaptive binning scheme.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Modelos Teóricos , Método de Monte Carlo , Aceleradores de Partículas/instrumentação , Imagens de Fantasmas , Fótons/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Radiometria/métodos , Dosagem Radioterapêutica
12.
New Microbes New Infect ; 14: 93-97, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27818775

RESUMO

Human infections associated with Corynebacterium kroppenstedtii are rarely reported, and this organism is usually described as antibiotic sensitive. Almost all published cases of C. kroppenstedtii infections have been associated with breast pathology in women and have been described in New Zealand, France, Canada, India and Japan. Here we describe the microbiologic characteristics of two strains isolated from two women diagnosed of granulomatous mastitis in Spain. One C. kroppenstedtii isolate was antibiotic sensitive while the other was multidrug resistant. Biochemical identification was possible using a wide battery of methods including API Coryne V2.0, API Strep, API NH, API NE, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene amplification and sequencing. Antimicrobial susceptibility to 28 antibiotics as determined by Etest showed one isolate being sensitive to benzylpenicillin, ciprofloxacin, moxifloxacin, gentamicin, vancomycin, clindamycin, tetracycline, linezolid and rifampin. The second isolate showed resistance to ciprofloxacin, moxifloxacin, clindamycin, tetracycline and rifampin. The multidrug-resistant isolate contained the erm(X), tet(W), cmx, aphA1-IAB, strAB and sul1 resistance genes known from the R plasmid pJA144188 of Corynebacterium resistens. These genes were absent in the genome of the antibiotic-sensitive isolate. This report confirms the tropism of this microorganism for women's breasts and presents the first description of a multidrug-resistant C. kroppenstedtii strain.

13.
New Microbes New Infect ; 10: 116-21, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26933505

RESUMO

During a 12-year period we isolated five Corynebacterium argentoratense strains identified by phenotypic methods, including the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and 16S rRNA gene sequencing. In addition, antimicrobial susceptibility was determined, and genome sequencing for the detection of antibiotic resistance genes was performed. The organisms were isolated from blood and throat cultures and could be identified by all methods used. All strains were resistant to cotrimoxazole, and resistance to ß-lactams was partly present. Two strains were resistant to erythromycin and clindamycin. The draft genome sequences of theses isolates revealed the presence of the erm(X) resistance gene that is embedded in the genetic structure of the transposable element Tn5423. Although rarely reported as a human pathogen, C. argentoratense can be involved in bacteraemia and probably in other infections. Our results also show that horizontal transfer of genes responsible for antibiotic resistance is occurring in this species.

14.
Phys Med Biol ; 50(16): 3739-54, 2005 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-16077224

RESUMO

In single photon emission computed tomography (SPECT) with parallel hole collimation, image reconstruction is usually performed as a set of bidimensional (2D) analytical or iterative reconstructions. This approach ignores the tridimensional (3D) nature of scatter and detector response function that affects the detected signal. To deal with the 3D nature of the image formation process, iterative reconstruction can be used by considering a 3D projector modelling the 3D spread of photons. In this paper, we investigate the value of using accurate Monte Carlo simulations to determine the 3D projector used in a fully 3D Monte Carlo (F3DMC) reconstruction approach. Given the 3D projector modelling all physical effects affecting the imaging process, the reconstruction problem is solved using the maximum likelihood expectation maximization (MLEM) algorithm. To validate the concept, three data sets were simulated and F3DMC was compared with two other 3D reconstruction strategies using analytical corrections for attenuation, scatter and camera point spread function. Results suggest that F3DMC improves spatial resolution, relative and absolute quantitation and signal-to-noise ratio. The practical feasibility of the approach on real data sets is discussed.


Assuntos
Tomografia Computadorizada de Emissão de Fóton Único/métodos , Algoritmos , Simulação por Computador , Estudos de Viabilidade , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Funções Verossimilhança , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Reprodutibilidade dos Testes , Espalhamento de Radiação , Estatística como Assunto , Tomografia Computadorizada de Emissão
15.
Leukemia ; 29(3): 705-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25102946

RESUMO

The development of resistance to therapy is unavoidable in the history of multiple myeloma patients. Therefore, the study of its characteristics and mechanisms is critical in the search for novel therapeutic approaches to overcome it. This effort is hampered by the absence of appropriate preclinical models, especially those mimicking acquired resistance. Here we present an in vivo model of acquired resistance based on the continuous treatment of mice bearing subcutaneous MM1S plasmacytomas. Xenografts acquired resistance to two generations of immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide) in combination with dexamethasone, that was reversible after a wash-out period. Furthermore, lenalidomide-dexamethasone (LD) or pomalidomide-dexamethasone (PD) did not display cross-resistance, which could be due to the differential requirements of the key target Cereblon and its substrates Aiolos and Ikaros observed in cells resistant to each combination. Differential gene expression profiles of LD and PD could also explain the absence of cross-resistance. Onset of resistance to both combinations was accompanied by upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway and addition of selumetinib, a small-molecule MEK inhibitor, could resensitize resistant cells. Our results provide insights into the mechanisms of acquired resistance to LD and PD combinations and offer possible therapeutic approaches to addressing IMiD resistance in the clinic.


Assuntos
Antineoplásicos/farmacologia , Dexametasona/farmacologia , Regulação Neoplásica da Expressão Gênica , Plasmocitoma/tratamento farmacológico , Talidomida/análogos & derivados , Proteínas Adaptadoras de Transdução de Sinal , Animais , Apoptose/efeitos dos fármacos , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Quimioterapia Combinada , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Lenalidomida , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Transplante de Neoplasias , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Plasmocitoma/genética , Plasmocitoma/metabolismo , Plasmocitoma/patologia , Transdução de Sinais , Talidomida/farmacologia , Transativadores/genética , Transativadores/metabolismo
16.
Phys Med Biol ; 49(2): 271-85, 2004 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-15083671

RESUMO

Monte Carlo simulations are increasingly used in scintigraphic imaging to model imaging systems and to develop and assess tomographic reconstruction algorithms and correction methods for improved image quantitation. GATE (GEANT4 application for tomographic emission) is a new Monte Carlo simulation platform based on GEANT4 dedicated to nuclear imaging applications. This paper describes the GATE simulation of a prototype of scintillation camera dedicated to small-animal imaging and consisting of a CsI(Tl) crystal array coupled to a position-sensitive photomultiplier tube. The relevance of GATE to model the camera prototype was assessed by comparing simulated 99mTc point spread functions, energy spectra, sensitivities, scatter fractions and image of a capillary phantom with the corresponding experimental measurements. Results showed an excellent agreement between simulated and experimental data: experimental spatial resolutions were predicted with an error less than 100 microns. The difference between experimental and simulated system sensitivities for different source-to-collimator distances was within 2%. Simulated and experimental scatter fractions in a [98-182 keV] energy window differed by less than 2% for sources located in water. Simulated and experimental energy spectra agreed very well between 40 and 180 keV. These results demonstrate the ability and flexibility of GATE for simulating original detector designs. The main weakness of GATE concerns the long computation time it requires: this issue is currently under investigation by the GEANT4 and the GATE collaborations.


Assuntos
Câmaras gama , Animais , Simulação por Computador , Processamento de Imagem Assistida por Computador , Método de Monte Carlo , Distribuição Normal , Imagens de Fantasmas , Espalhamento de Radiação , Sensibilidade e Especificidade , Software
17.
Phys Med Biol ; 49(19): 4543-61, 2004 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-15552416

RESUMO

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.


Assuntos
Simulação por Computador , Software , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Método de Monte Carlo , Reprodutibilidade dos Testes , Termodinâmica
18.
Rev Neurol ; 35(5): 404-7, 2002.
Artigo em Espanhol | MEDLINE | ID: mdl-12373669

RESUMO

OBJECTIVE: To know the frequency of Todd s paralysis during the video EEG monitoring studies, to investigate in its pathophysiology, and to confirm its value to localise the epileptic focus. PATIENTS AND METHODS: We reviewed 114 monitoring studies, in 102 patients. RESULTS: Sixty patients had epileptic seizures. An obvious paresis was noted in four seizures of two patients (3 and 1, respectively). Both patients had frontal epilepsy. During the paralysis, in the first patient the EEG showed ictal discharges on the contralateral centrotemporal area. In the second patient, the EEG demonstrated slow waves in the contralateral frontal region. The ictal onset was contralateral to the paresis in all cases. No patient with pseudoseizures had paralysis. CONCLUSIONS: Postconvulsive paralysis are not frequent in video EEG monitoring studies. However, if present it points out to a contralateral seizure onset. In our series it happened in patients with frontal seizures. The EEG may help to clarify if it correspond to a true postictal phenomenon or to a ictal paralysis.


Assuntos
Eletroencefalografia , Paralisia/fisiopatologia , Gravação em Vídeo , Adulto , Criança , Feminino , Humanos
19.
Phys Med Biol ; 58(10): 3433-59, 2013 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-23618944

RESUMO

This work investigates the possibility of combining Monte Carlo (MC) simulations to a denoising algorithm for the accurate prediction of images acquired using amorphous silicon (a-Si) electronic portal imaging devices (EPIDs). An accurate MC model of the Siemens OptiVue1000 EPID was first developed using the penelope code, integrating a non-uniform backscatter modelling. Two already existing denoising algorithms were then applied on simulated portal images, namely the iterative reduction of noise (IRON) method and the locally adaptive Savitzky-Golay (LASG) method. A third denoising method, based on a nonparametric Bayesian framework and called DPGLM (for Dirichlet process generalized linear model) was also developed. Performances of the IRON, LASG and DPGLM methods, in terms of smoothing capabilities and computation time, were compared for portal images computed for different values of the RMS pixel noise (up to 10%) in three different configurations, a heterogeneous phantom irradiated by a non-conformal 15 × 15 cm(2) field, a conformal beam from a pelvis treatment plan, and an IMRT beam from a prostate treatment plan. For all configurations, DPGLM outperforms both IRON and LASG by providing better smoothing performances and demonstrating a better robustness with respect to noise. Additionally, no parameter tuning is required by DPGLM, which makes the denoising step very generic and easy to handle for any portal image. Concerning the computation time, the denoising of 1024 × 1024 images takes about 1 h 30 min, 2 h and 5 min using DPGLM, IRON, and LASG, respectively. This paper shows the feasibility to predict within a few hours and with the same resolution as real images accurate portal images, combining MC simulations with the DPGLM denoising algorithm.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Método de Monte Carlo , Radioterapia Guiada por Imagem/métodos , Equipamentos e Provisões Elétricas , Humanos , Masculino , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/radioterapia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador
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