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1.
Proc Natl Acad Sci U S A ; 114(34): 9170-9175, 2017 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-28790187

RESUMO

The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (104 cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.


Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Análise de Célula Única/métodos , Escherichia coli Uropatogênica/efeitos dos fármacos , Ciprofloxacina/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Testes Imediatos/normas , Reprodutibilidade dos Testes , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/classificação , Escherichia coli Uropatogênica/fisiologia
2.
Bioinformatics ; 32(15): 2394-5, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27153711

RESUMO

UNLABELLED: SMeagol is a software tool to simulate highly realistic microscopy data based on spatial systems biology models, in order to facilitate development, validation and optimization of advanced analysis methods for live cell single molecule microscopy data. AVAILABILITY AND IMPLEMENTATION: SMeagol runs on Matlab R2014 and later, and uses compiled binaries in C for reaction-diffusion simulations. Documentation, source code and binaries for Mac OS, Windows and Ubuntu Linux can be downloaded from http://smeagol.sourceforge.net CONTACT: johan.elf@icm.uu.se SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Imagem Individual de Molécula , Software , Linguagens de Programação , Biologia de Sistemas
3.
Proc SPIE Int Soc Opt Eng ; 7962: 79620S, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-23066452

RESUMO

The use of regional connectivity measurements derived from diffusion imaging datasets has become of considerable interest in the neuroimaging community in order to better understand cortical and subcortical white matter connectivity. Current connectivity assessment methods are based on streamline fiber tractography, usually applied in a Monte-Carlo fashion. In this work we present a novel, graph-based method that performs a fully deterministic, efficient and stable connectivity computation. The method handles crossing fibers and deals well with multiple seed regions. The computation is based on a multi-directional graph propagation method applied to sampled orientation distribution function (ODF), which can be computed directly from the original diffusion imaging data. We show early results of our method on synthetic and real datasets. The results illustrate the potential of our method towards subject-specific connectivity measurements that are performed in an efficient, stable and reproducible manner. Such individual connectivity measurements would be well suited for application in population studies of neuropathology, such as Autism, Huntington's Disease, Multiple Sclerosis or leukodystrophies. The proposed method is generic and could easily be applied to non-diffusion data as long as local directional data can be derived.

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