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1.
Nucleic Acids Res ; 49(D1): D1207-D1217, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33264411

RESUMO

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.


Assuntos
Ontologias Biológicas , Biologia Computacional/métodos , Bases de Dados Factuais , Doença/genética , Genoma , Fenótipo , Software , Animais , Modelos Animais de Doenças , Genótipo , Humanos , Recém-Nascido , Cooperação Internacional , Internet , Triagem Neonatal/métodos , Farmacogenética/métodos , Terminologia como Assunto
2.
J Genet Couns ; 27(2): 358-369, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29204811

RESUMO

"The objective of this study was to" test the effectiveness of an enhanced genomic report on patient-centered outcome domains including communication, engagement and satisfaction. "Study design utilized" a prospective, randomized, mixed-methods desctiptive study of a whole genome sequencing results report, GenomeCOMPASS™, that was accessed by providers through the electronic health record and by patients through the associated patient portal. "The study was set in" an integrated healthcare delivery system in central Pennsylvania. "Eighty-four" parents of 46 children with undiagnosed Intellectual Disability, Autism Spectrum Disorder and/or multiple congenital anomalies who had participated in a previous study offering whole genome sequencing for their affected child were invited to enroll. Fifty-two parents enrolled. Following a traditional genetics results informing visit, the study coordinator stratified families by diagnostic result and uninformative result and then randomized families within each group to an intervention arm to receive the GenomeCOMPASS™ report or to the usual care arm to receive a summary letter from the medical geneticist. A letter inviting enrollment included a baseline survey, which once returned, constituted enrollment. Surveys were administered at 3 months post-genetics visit. At 6 months, the usual care arm crossed over to receive the intervention and were administered an additional survey at 3 months. Qualitative interviews were conducted following survey completion to augment the survey data regarding the patient centered outcomes of interest. Patient reported outcomes including communication, engagement, empowerment and satisfaction. In the intervention arm, GenomeCOMPASS™ reports were released to 14 families (N = 28 parents) and of those 21 (75%) returned 3 month surveys. In the usual care arm, 12 families (N = 24 parents) received usual care summary letters and of those 20 (83%) returned 3 month surveys. At crossover, GenomeCOMPASS™ reports were released to 20 individuals and 15 (75%) returned 3 month surveys. Qualitative interviews were conducted with 5 individuals. Use of the GenomeCOMPASS™ report was reported by this small group of parents to improve communication with providers and non-health professionals such as educators and therapists and led to increased engagement and high satisfaction. Providers and others involved in the children's care also endorsed the report's effectiveness. Reports that addressed negative findings, i.e. uninformative results, were not found to be useful. Although the number of users was small, this study supports that customizable template reports may provide a useful and durable source of information that can support and enhance the information provided by genetics professionals in traditional face-to-face encounters. TRIAL REGISTRATION: Clinicaltrials.gov (Record 2013-0594).


Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Comunicação , Testes Genéticos , Genômica , Satisfação do Paciente , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pais , Assistência Centrada no Paciente , Estudos Prospectivos , Inquéritos e Questionários
3.
Am J Med Genet A ; 170A(5): 1134-41, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26842872

RESUMO

This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi-structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider-oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time.


Assuntos
Genômica/normas , Comunicação em Saúde , Pessoal de Saúde , Análise de Sequência de DNA/normas , Feminino , Genoma Humano , Humanos , Entrevistas como Assunto , Masculino , Pacientes , Médicos
4.
Am J Med Genet A ; 167A(10): 2238-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26086630

RESUMO

The purpose of this study was to develop a family genomic laboratory report designed to communicate genome sequencing results to parents of children who were participating in a whole genome sequencing clinical research study. Semi-structured interviews were conducted with parents of children who participated in a whole genome sequencing clinical research study to address the elements, language and format of a sample family-directed genome laboratory report. The qualitative interviews were followed by two focus groups aimed at evaluating example presentations of information about prognosis and next steps related to the whole genome sequencing result. Three themes emerged from the qualitative data: (i) Parents described a continual search for valid information and resources regarding their child's condition, a need that prior reports did not meet for parents; (ii) Parents believed that the Family Report would help facilitate communication with physicians and family members; and (iii) Parents identified specific items they appreciated in a genomics Family Report: simplicity of language, logical flow, visual appeal, information on what to expect in the future and recommended next steps. Parents affirmed their desire for a family genomic results report designed for their use and reference. They articulated the need for clear, easy to understand language that provided information with temporal detail and specific recommendations regarding relevant findings consistent with that available to clinicians.


Assuntos
Testes Genéticos , Deficiência Intelectual/diagnóstico , Relações Médico-Paciente/ética , Relatório de Pesquisa/tendências , Adulto , Criança , Mapeamento Cromossômico , Grupos Focais , Estudo de Associação Genômica Ampla , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Pais/psicologia , Prognóstico , Pesquisa Qualitativa , Inquéritos e Questionários , Terminologia como Assunto
5.
Psychopharmacol Bull ; 52(3): 20-30, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35815177

RESUMO

Objectives: The mechanism of many neuropsychiatric disorders remains unknown, but the ineffectiveness of the sodium channel blocker lidocaine has been suggested to be a biomarker for Attention Deficit Hyperactivity Disorder (ADHD) and a severe form of Premenstrual Syndrome (PMS) that is considered psychiatric. We conducted single-arm double-blind clinical trials to test whether lidocaine ineffectiveness can be used as a biomarker to identify people with these conditions and provide a clue as to the molecular mechanism and potential psychopharmacological intervention. Experimental Design: We developed a noninvasive taste test for lidocaine ineffectiveness, validated by comparing lidocaine injections to pain testing in 12 subjects, and assessed it in individuals with ADHD and PMS. Principal Observations: Lidocaine ineffectiveness had a strong association in women with ADHD + PMS in a sample of 53 subjects and controls (p < 0.001). Conclusions: These results suggest the possibility of the biological understanding of the combination of ADHD and PMS that is characteristic of the psychiatric disorder Premenstrual Dysphoric Disorder (PMDD). These results and comparison to family pedigrees of a neuromuscular channelopathy with overlapping symptoms suggest the possibility that the clinical phenotype in PMDD is produced by sensory overstimulation, and amenable to molecular understanding and treatment.


Assuntos
Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Psicofarmacologia , Feminino , Humanos , Lidocaína/farmacologia , Personalidade , Transtorno Disfórico Pré-Menstrual/tratamento farmacológico , Síndrome Pré-Menstrual/tratamento farmacológico , Síndrome Pré-Menstrual/psicologia , Método Duplo-Cego
6.
BMJ Health Care Inform ; 28(1)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33962988

RESUMO

OBJECTIVES: There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems. METHODS: We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation. RESULTS: Six individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%-50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems. CONCLUSION: This study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.


Assuntos
Sistemas de Apoio a Decisões Clínicas/organização & administração , Registros Eletrônicos de Saúde/organização & administração , Genômica/organização & administração , Humanos , Processamento de Linguagem Natural , Terminologia como Assunto , Fatores de Tempo , Design Centrado no Usuário
7.
Orphanet J Rare Dis ; 15(1): 191, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698834

RESUMO

BACKGROUND: In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a diagnosis based on the complete set of variants provided by the lab. We tested a software approach to assist the clinician in making the diagnosis based on clinical findings and an annotated genomic variant table, using cases already solved using less automated processes. RESULTS: For the 81 cases studied (involving 216 individuals), 70 had genetic abnormalities with phenotypes previously described in the literature, and 11 were not described in the literature at the time of analysis ("discovery genes"). These included cases beyond a trio, including ones with different variants in the same gene. In 100% of cases the abnormality was recognized. Of the 70, the abnormality was ranked #1 in 94% of cases, with an average rank 1.1 for all cases. Large CNVs could be analyzed in an integrated analysis, performed in 24 of the cases. The process is rapid enough to allow for periodic reanalysis of unsolved cases. CONCLUSIONS: A clinician-friendly environment for clinical correlation can be provided to clinicians who are best positioned to have the clinical information needed for this interpretation.


Assuntos
Doenças Raras , Software , Variações do Número de Cópias de DNA , Genômica , Humanos , Fenótipo , Doenças Raras/diagnóstico , Doenças Raras/genética
8.
J Child Neurol ; 22(12): 1408-10, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18174562

RESUMO

This report describes 2 generations of a family with symptoms of sensory overstimulation that exhibit a potassium sensitivity similar to that seen in hypokalemic periodic paralysis. The sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate, with onset of the therapeutic effect in approximately 20 minutes. The effect of potassium is reminiscent of its effect in the channelopathies underlying hypokalemic periodic paralysis, and the resistance to lidocaine applied peripherally suggests a peripheral sensory localization to the abnormality. The phenotype overlaps with that of attention deficit disorder, raising the possibility of subtypes of attention deficit disorder that have a peripheral sensory cause and novel forms of therapy.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Hipopotassemia/complicações , Compostos de Potássio/administração & dosagem , Transtornos de Sensação/complicações , Estimulação Acústica/efeitos adversos , Adolescente , Anestésicos Locais/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Diagnóstico Diferencial , Resistência a Medicamentos , Feminino , Gluconatos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/tratamento farmacológico , Lidocaína/farmacologia , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/efeitos adversos , Compostos de Potássio/sangue , Transtornos de Sensação/tratamento farmacológico
9.
EGEMS (Wash DC) ; 5(1): 23, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29930964

RESUMO

INTRODUCTION: Reducing misdiagnosis has long been a goal of medical informatics. Current thinking has focused on achieving this goal by integrating diagnostic decision support into electronic health records. METHODS: A diagnostic decision support system already in clinical use was integrated into electronic health record systems at two large health systems, after clinician input on desired capabilities. The decision support provided three outputs: editable text for use in a clinical note, a summary including the suggested differential diagnosis with a graphical representation of probability, and a list of pertinent positive and pertinent negative findings (with onsets). RESULTS: Structured interviews showed widespread agreement that the tool was useful and that the integration improved workflow. There was disagreement among various specialties over the risks versus benefits of documenting intermediate diagnostic thinking. Benefits were most valued by specialists involved in diagnostic testing, who were able to use the additional clinical context for richer interpretation of test results. Risks were most cited by physicians making clinical diagnoses, who expressed concern that a process that generated diagnostic possibilities exposed them to legal liability. DISCUSSION AND CONCLUSION: Reconciling the preferences of the various groups could include saving only the finding list as a patient-wide resource, saving intermediate diagnostic thinking only temporarily, or adoption of professional guidelines to clarify the role of decision support in diagnosis.

10.
J Child Neurol ; 21(7): 595-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16970851

RESUMO

Medical computing has been split between palm-sized computers optimized for mobility and desktop computers optimized for capability. This split was due to technology too immature to deliver both mobility and capability in the same computer and the lack of medical software that demanded both mobility and capability. Advances in hardware and software are ushering in an era in which fully capable computers will be available ubiquitously. As a result, medical practice, education and publishing will change. Medical practice will be improved by the use of software that not only assists with diagnosis but can do so at the bedside, where the doctor can act immediately upon suggestions such as useful findings to check. Medical education will shift away from a focus on details of unusual diseases and toward a focus on skills of physical examination and using computerized tools. Medical publishing, in contrast, will shift toward greater detail: it will be increasingly important to quantitate the frequency of findings in diseases and their time course since such information can have a major impact clinically when added to decision support software.


Assuntos
Educação Médica , Informática Médica , Doenças do Sistema Nervoso/diagnóstico , Editoração , Criança , Metodologias Computacionais , Humanos , Sistemas Automatizados de Assistência Junto ao Leito
11.
Pediatr Rheumatol Online J ; 14(1): 67, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27964737

RESUMO

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ("unaided"), versus after use of the DDSS ("aided"). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p < 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an "open book" approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists' ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086.


Assuntos
Técnicas de Apoio para a Decisão , Medicina Baseada em Evidências , Doenças Reumáticas/diagnóstico , Software , Criança , Erros de Diagnóstico/prevenção & controle , Humanos
12.
J Child Neurol ; 30(7): 881-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25156663

RESUMO

We describe an "integrated genome-phenome analysis" that combines both genomic sequence data and clinical information for genomic diagnosis. It is novel in that it uses robust diagnostic decision support and combines the clinical differential diagnosis and the genomic variants using a "pertinence" metric. This allows the analysis to be hypothesis-independent, not requiring assumptions about mode of inheritance, number of genes involved, or which clinical findings are most relevant. Using 20 genomic trios with neurologic disease, we find that pertinence scores averaging 99.9% identify the causative variant under conditions in which a genomic trio is analyzed and family-aware variant calling is done. The analysis takes seconds, and pertinence scores can be improved by clinicians adding more findings. The core conclusion is that automated genome-phenome analysis can be accurate, rapid, and efficient. We also conclude that an automated process offers a methodology for quality improvement of many components of genomic analysis.


Assuntos
Estudos de Associação Genética , Testes Genéticos/métodos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Simulação por Computador , Família , Variação Genética , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Reconhecimento Automatizado de Padrão , Fenótipo
13.
Novartis Found Symp ; 241: 173-80; discussion 180-8, 226-32, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11771645

RESUMO

We examined the electrophysiology of epilepsy in the simplest system that exhibits epileptiform activity: microisland cultures that contain only one neuron. Some of these solitary excitatory hippocampal neurons generate the 'ictal' epileptiform activity characteristic of seizures. These neurons have endogenous (non-transmitter-mediated) bursts of activity that last for many seconds and appear to be driven by a persistent Na+ current. We examined this persistent Na+ current at the single channel level by recording the late openings of Na+ channels using outside-out patch recordings. Phenytoin reduced the probability of these late channel openings, but had less effect on the early channel openings that make up the peak Na+ current. The reduction of late channel openings was larger with pulses to more depolarized voltages. In contrast, the effect on early channel openings was similar at all voltages. There was little effect of phenytoin on the duration of channel openings and no effect on open channel current. This suggests that the persistent Na+ current is crucial in generating seizures. A good strategy for selecting anticonvulsants may be to search for drugs that more selectively block the persistent Na+ current at depolarized voltages. Such drugs could combine effectiveness and reduced side effects.


Assuntos
Epilepsia/fisiopatologia , Canais de Sódio/fisiologia , Animais , Eletrofisiologia/métodos , Humanos , Ativação do Canal Iônico/fisiologia , Convulsões/fisiopatologia
14.
J Child Neurol ; 29(4): 487-92, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23576414

RESUMO

Using vignettes of real cases and the SimulConsult diagnostic decision support software, neurologists listed a differential diagnosis and workup before and after using the decision support. Using the software, there was a significant reduction in error, up to 75% for diagnosis and 56% for workup. This error reduction occurred despite the baseline being one in which testers were allowed to use narrative resources and Web searching. A key factor that improved performance was taking enough time (>2 minutes) to enter clinical findings into the software accurately. Under these conditions and for instances in which the diagnoses changed based on using the software, diagnostic accuracy improved in 96% of instances. There was a 6% decrease in the number of workup items accompanied by a 34% increase in relevance. The authors conclude that decision support for a neurological diagnosis can reduce errors and save on unnecessary testing.


Assuntos
Tomada de Decisões Assistida por Computador , Erros de Diagnóstico/prevenção & controle , Medicina Baseada em Evidências , Doenças do Sistema Nervoso/diagnóstico , Diagnóstico Diferencial , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Internet , Masculino , Software
15.
Appl Transl Genom ; 6: 26-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27054075
18.
J Neurosci Res ; 71(2): 237-45, 2003 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-12503086

RESUMO

We examined the vulnerability to excitotoxicity of rat oligodendrocytes in dissociated cell culture at different developmental stages. Mature oligodendrocytes that express myelin basic protein were resistant to excitotoxic injury produced by kainate, whereas earlier stages in the oligodendrocyte lineage were vulnerable to this insult. To test the hypothesis that the sensitivity of immature oligodendrocytes and the resistance of mature oligodendrocytes to kainate toxicity were due to differences in membrane responsiveness to kainate, we used whole-cell patch-clamp recording. Oligodendrocyte precursors in cultures vulnerable to kainate toxicity responded to 500 microM kainate with large inward currents, whereas mature myelin basic protein-expressing oligodendrocytes in cultures resistant to kainate toxicity showed no clear response to application of this agonist. We assayed expression of glutamate receptor subunits (GluR) -2, -4, -6, -7, and KA2 using immunoblot analysis and found that expression of all of these glutamate receptors was significantly down-regulated in mature oligodendrocytes. These results suggest a striking developmental regulation of glutamate receptors in oligodendrocytes and suggest that the vulnerability of oligodendrocytes to non- N-methyl-D-aspartate receptor-mediated excitotoxicity might be much greater in developing oligodendrocytes than after the completion of myelination.


Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Caínico/farmacologia , Proteína Básica da Mielina/metabolismo , Oligodendroglia/efeitos dos fármacos , Receptores de Glutamato/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Animais Recém-Nascidos , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Fator Neurotrófico Ciliar/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Interações Medicamentosas , Eletrofisiologia/métodos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fatores de Crescimento de Fibroblastos/farmacologia , Immunoblotting , Imuno-Histoquímica , Proteína Básica da Mielina/efeitos dos fármacos , Oligodendroglia/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato/classificação , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia
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