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1.
Nat Neurosci ; 22(7): 1066-1074, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209380

RESUMO

Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10-12) that replicates in an independent population (Preplication = 3.27 × 10-3, Pmeta-analysis = 9.09 × 10-12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.


Assuntos
Abuso de Maconha/genética , Proteínas do Tecido Nervoso/fisiologia , Receptores Nicotínicos/fisiologia , Idade de Início , Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Encéfalo/metabolismo , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Cognição/fisiologia , Estudos de Coortes , Fatores de Confusão (Epidemiologia) , Dinamarca , Escolaridade , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Islândia , Masculino , Herança Multifatorial , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Receptores Nicotínicos/biossíntese , Receptores Nicotínicos/genética , Esquizofrenia/genética , Fumar/genética , Transcriptoma
2.
Int J Infect Dis ; 71: 53-55, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29653201

RESUMO

OBJECTIVES: The serological detection of IgM antibodies is the most widely used test to diagnose scrub typhus infection. However, the kinetics of IgM and IgG antibodies post-infection remain elusive, which could contribute to false positivity. The objective of this study was to document the nature of the evolution of these antibody titres after infection. METHODS: Adult patients previously confirmed to have scrub typhus by IgM ELISA, positive PCR, or both, were included in this cross-sectional study. The levels of IgM and IgG antibodies in serum samples were tested using an ELISA and the distribution curve was plotted. RESULTS: Two hundred and three patients were included in this study. Post-infection serum sampling was done between 1 month and 46 months after documented infection. IgM levels declined gradually but remained elevated above the diagnostic cut-off for up to 12 months post-infection. However, IgG levels continued to rise reaching a peak at 10 months, followed by a gradual decline over several months. In the majority of cases, the IgG levels remained above the cut-off threshold for more than 36 months. CONCLUSIONS: Clinicians need to be cautious in using a single serum sample for the detection of IgM to diagnose scrub typhus, as it remains elevated for up to 12 months after the infection, whereas the serum IgG level could be used as an indicator of past infection.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Tifo por Ácaros/diagnóstico , Adulto , Estudos Transversais , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Tifo por Ácaros/imunologia
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