RESUMO
Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.
Assuntos
Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Estudos de Coortes , Diagnóstico Tardio , Diagnóstico Diferencial , Doença Granulomatosa Crônica/metabolismo , Humanos , NADPH Oxidase 2/genética , NADPH Oxidases/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
This work synthetically documents the history of women's efforts to be professionally acknowledged as surgeon. The examined timeline goes back from ancient civilizations to our days. It highlights the difficulties that women have had in time, particularly in the last two centuries, trying to make their aspirations come true and their will in becoming surgeons. The attention goes to the difficulties that are faced in our time regarding the medical field and the academic career. Moreover, corrective organizational and behavioural advice is given to solve specific problems still actual, in order to promote sex equality and working collaboration.
Assuntos
Cirurgia Geral/história , Médicas/história , Cultura , Antigo Egito , Europa (Continente) , Feminino , Identidade de Gênero , Grécia Antiga , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Humanos , América do Norte , Cidade de Roma , SexismoRESUMO
Common variable immunodeficiency (CVID) is considered the most common symptomatic antibody deficiency and, although mainly reported in adults, it may present from childhood. Few data on the impact of TACI defects on the clinical and immunological status of children are available. We screened 42 hypogammaglobulinemic children to investigate the frequency and mutational features of TACI defects. The genetic, clinical and immunological characterization was extended to 31 relatives of 11 children with TACI mutations. Of interest, our analysis showed a considerably higher mutation frequency in hypogammaglobulinemic children (13/42; 31%) than in other cohorts of adult patients. In seven out of nine families with the C104R variant, the prevalence of autoimmunity was significantly higher in C104R heterozygous relatives (8/15; 53%) than in those with no C104R mutation (1/11; 9%). Our data suggest a different impact of TACI mutations, from hypogammaglobulinemia in children to autoimmune disease in adulthood.
Assuntos
Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Autoimunidade/genética , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Mutação , Proteína Transmembrana Ativadora e Interagente do CAML/genética , Adolescente , Adulto , Fatores Etários , Idoso , Envelhecimento/genética , Envelhecimento/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Adulto JovemRESUMO
BACKGROUND: Inappropriateness of upper endoscopy (EGD) indication causes decreased diagnostic yield. Our aim of was to identify predictors of appropriateness rate for EGD among endoscopic centres. METHODS: A post-hoc analysis of two multicentre cross-sectional studies, including 6270 and 8252 patients consecutively referred to EGD in 44 (group A) and 55 (group B) endoscopic Italian centres in 2003 and 2007, respectively, was performed. A multiple forward stepwise regression was applied to group A, and independently validated in group B. A <70% threshold was adopted to define inadequate appropriateness rate clustered by centre. RESULTS: discrete variability of clustered appropriateness rates among the 44 group A centres was observed (median: 77%; range: 41-97%), and a <70% appropriateness rate was detected in 11 (25%). Independent predictors of centre appropriateness rate were: percentage of patients referred by general practitioners (GP), rate of urgent examinations, prevalence of relevant diseases, and academic status. For group B, sensitivity, specificity and area under receiver operating characteristic curve of the model in detecting centres with a <70% appropriateness rate were 54%, 93% and 0.72, respectively. CONCLUSIONS: A simple predictive rule, based on rate of patients referred by GPs, rate of urgent examinations, prevalence of relevant diseases and academic status, identified a small subset of centres characterised by a high rate of inappropriateness. These centres may be presumed to obtain the largest benefit from targeted educational programs.