RESUMO
Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.
Assuntos
Artrite Juvenil/tratamento farmacológico , Metotrexato/uso terapêutico , Artrite Juvenil/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Decision analysis has wide application across disciplines. The purpose of engaging in formal analysis is to enhance the understanding and description of problems, aiding the decision maker to be more explicit and more comprehensive in the search for a preferred course of action. Legal considerations arise out of clinical decisions. The legal implications are illustrated with actual applicable issues arising out of current dental litigations.
Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Assistência Odontológica/legislação & jurisprudência , Assistência Odontológica/normas , Responsabilidade Legal , Humanos , ImperíciaRESUMO
The adrenocortical gland is one of the most vascularized organs of the mammalian body. It undergoes continuous morphological changes dynamically dependent upon special permeability conditions related to various physiological and physiopathological events. The adrenal cortex of different adult mammals (3 pigs, 2 mice, 3 sheep) was studied by means of scanning (SEM) and transmission (TEM) electron microscopy. As seen by SEM it is formed of polyhedral cells which delimit a characteristic continuous labyrinth system of intercellular lacunae occupied by sinusoid-like capillaries. The capillary wall is fenestrated and is lined by flattened endothelial cells with their nuclear part bulging into the capillary lumen. The fenestrae are round or oval pores measuring 50-100 nm in diameter. They are usually clustered to form sieve plates and characteristically present a thin membranous diaphragm. Irregular microelevations and dome-like projections are often seen. These structures are made of thin cytoplasmic plates interrupted by numerous small pores which show a sieve plate profile. The pored-domes on the nuclear portion seem to be identical in structure to those found in the thinner endothelial part; some of them appear to detach from the endothelial cell. The pored-domes are structurally comparable to those reported both in the renal glomerular endothelium and in liver sinusoids. These endothelial structures may be an expression of the high rate of filtration of these tissues and may be also related to the final step of the replacement of the sieve plates during endothelial regeneration.
Assuntos
Córtex Suprarrenal/irrigação sanguínea , Capilares/ultraestrutura , Células Endoteliais/ultraestrutura , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/ultraestrutura , Animais , Capilares/fisiologia , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Permeabilidade da Membrana Celular/fisiologia , Núcleo Celular/fisiologia , Núcleo Celular/ultraestrutura , Citoplasma/fisiologia , Citoplasma/ultraestrutura , Células Endoteliais/fisiologia , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Regeneração/fisiologia , Ovinos , Sus scrofaRESUMO
Human ability to switch from one cognitive task to another involves both endogenous preparation without an external stimulus and exogenous adjustment in response to the external stimulus. In an event-related functional MRI study, participants performed pairs of two tasks that are either the same (task repetition) or different (task switch) from each other. On half of the trials, foreknowledge about task repetition or task switch was available. On the other half, it was not. Endogenous preparation seems to involve lateral prefrontal cortex (BA 46/45) and posterior parietal cortex (BA 40). During preparation, higher activation increases in inferior lateral prefrontal cortex and superior posterior parietal cortex were associated with foreknowledge than with no foreknowledge. Exogenous adjustment seems to involve superior prefrontal cortex (BA 8) and posterior parietal cortex (BA 39/40) in general. During a task switch with no foreknowledge, activations in these areas were relatively higher than during a task repetition with no foreknowledge. These results suggest that endogenous preparation and exogenous adjustment for a task switch may be independent processes involving different brain areas.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Cognição/fisiologia , Aprendizagem/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Conhecimento , Imageamento por Ressonância Magnética , MasculinoRESUMO
Event-related fMRI was used to dissociate the neural systems involved in category learning with and without awareness. Ten subjects performed a speeded response category learning task. Functional MR images were acquired during both explicit and implicit learning conditions. Behavioral data showed evidence of learning in both conditions. Functional imaging data showed different activation patterns in implicit and explicit trials. Decreased activation in extrastriate region V3 was found with implicit learning, and increased activation in V3, the medial temporal lobe, and frontal regions were found with explicit learning. These results support the theory that implicit and explicit learning utilize dissociable neural systems. Moreover, in both the implicit and explicit conditions a similar pattern of decreased activation was found in parietal regions. This commonality suggests that these dissociable systems also operate in parallel.