RESUMO
BACKGROUND: Inhaled corticosteroid (ICS) response among patients with asthma is influenced by genetics, but biologically actionable insights based on associations have not been found. Various glucocorticoid response omics data sets are available to interrogate their biological effects. OBJECTIVE: We sought to identify functionally relevant ICS-response genetic associations by integrating complementary multiomics data sets. METHODS: Variants with P values less than 10-4 from a previous ICS-response genome-wide association study were reranked on the basis of integrative scores determined from (1) glucocorticoid receptor- and (2) RNA polymerase II-binding regions inferred from ChIP-Seq data for 3 airway cell types, (3) glucocorticoid response element motifs, (4) differentially expressed genes in response to glucocorticoid exposure according to 20 transcriptomic data sets, and (5) expression quantitative trait loci from GTEx. Candidate variants were tested for association with ICS response and asthma in 6 independent studies. RESULTS: Four variants had significant (q value < 0.05) multiomics integrative scores. These variants were in a locus consisting of 52 variants in high linkage disequilibrium (r2 ≥ 0.8) near glucocorticoid receptor-binding sites by the gene BIRC3. Variants were also BIRC3 expression quantitative trait loci in lung, and 2 were within/near putative glucocorticoid response element motifs. BIRC3 had increased RNA polymerase II occupancy and gene expression, with glucocorticoid exposure in 2 ChIP-Seq and 13 transcriptomic data sets. Some BIRC3 variants in the 52-variant locus were associated (P < .05) with ICS response in 3 independent studies and others with asthma in 1 study. CONCLUSIONS: BIRC3 should be prioritized for further functional studies of ICS response.
Assuntos
Asma , Glucocorticoides , Corticosteroides , Asma/genética , Asma/metabolismo , Proteína 3 com Repetições IAP de Baculovírus/genética , Estudo de Associação Genômica Ampla , Glucocorticoides/farmacologia , Humanos , Pulmão/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Polimerase II/genética , Receptores de Glucocorticoides/genéticaRESUMO
OBJECTIVES: To assess the prognostic role of hepatitis in pediatric patients with aplastic anemia and the incidence of hepatitis B among patients with hepatitis-associated aplastic anemia in an area with a previously high prevalence of hepatitis B after nationwide hepatitis B vaccination for 30 years. STUDY DESIGN: Pediatric patients (n = 78) with aplastic anemia were enrolled in this study, including 9 with hepatitis-associated aplastic anemia. We collected the clinical characteristics, etiologies of the aplastic anemia, hepatitis B virus serology and serum hepatitis B viral load, response to the treatments, and survival outcome from the participants. We applied univariate and multivariate Cox regression analysis to evaluate the correlations between clinical features and survival outcome. Survival analysis was done using Cox regression model and Kaplan-Meier curves. RESULTS: Patients with hepatitis-associated aplastic anemia were related to significantly worse survival prognosis when compared with patients with non-hepatitis-associated aplastic anemia, and hepatitis-associated aplastic anemia was the only independent prognostic factor to predict a poor survival outcome in our patients with aplastic anemia by multivariable analysis. In none of the total 78 patients was aplastic anemia related to hepatitis B virus infection. CONCLUSIONS: Patients with hepatitis-associated aplastic anemia had a significantly worse prognosis when compared with patients whose aplastic anemia was not hepatitis-associated. This study demonstrates the potential benefit of hepatitis B vaccination in decreasing the incidence of hepatitis-associated aplastic anemia in children.
Assuntos
Anemia Aplástica/virologia , Hepatite B/complicações , Adolescente , Anemia Aplástica/sangue , Anemia Aplástica/etiologia , Anemia Aplástica/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , TaiwanRESUMO
OBJECTIVE: To determine the range of motion and stability of the human cadaveric cervical spine after the implantation of a novel artificial disc and vertebra system by comparing an intact group and a fusion group. METHODS: Biomechanical tests were conducted on 18 human cadaveric cervical specimens. The range of motion and the stability index range of motion were measured to study the function and stability of the artificial disc and vertebra system of the intact group compared with the fusion group. RESULTS: In all cases, the artificial disc and vertebra system maintained intervertebral motion and reestablished vertebral height at the operative level. After its implantation, there was no significant difference in the range of motion (ROM) of C(3-7) in all directions in the non-fusion group compared with the intact group (p>0.05), but significant differences were detected in flexion, extension and axial rotation compared with the fusion group (p<0.05). The ROM of adjacent segments (C(3-4), C(6-7)) of the non-fusion group decreased significantly in some directions compared with the fusion group (p<0.05). Significant differences in the C(4-6) ROM in some directions were detected between the non-fusion group and the intact group. In the fusion group, the C(4-6) ROM in all directions decreased significantly compared with the intact and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some directions was negative in the non-fusion group, and a significant difference in SI-ROM was only found in the C(4-6) segment of the non-fusion group compared with the fusion group. CONCLUSION: An artificial disc and vertebra system could restore vertebral height and preserve the dynamic function of the surgical area and could theoretically reduce the risk of adjacent segment degeneration compared with the anterior fusion procedure. However, our results should be considered with caution because of the low power of the study. The use of a larger sample should be considered in future studies.
Assuntos
Cadáver , Próteses e Implantes , Doenças da Medula Espinal/cirurgia , Fusão Vertebral/instrumentação , Adulto , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica , Feminino , Humanos , Masculino , Implantação de Prótese , Fusão Vertebral/métodosRESUMO
OBJECTIVE: To determine the range of motion and stability of the human cadaveric cervical spine after the implantation of a novel artificial disc and vertebra system by comparing an intact group and a fusion group. METHODS: Biomechanical tests were conducted on 18 human cadaveric cervical specimens. The range of motion and the stability index range of motion were measured to study the function and stability of the artificial disc and vertebra system of the intact group compared with the fusion group. RESULTS: In all cases, the artificial disc and vertebra system maintained intervertebral motion and reestablished vertebral height at the operative level. After its implantation, there was no significant difference in the range of motion (ROM) of C3-7 in all directions in the non-fusion group compared with the intact group (p>0.05), but significant differences were detected in flexion, extension and axial rotation compared with the fusion group (p<0.05). The ROM of adjacent segments (C3-4, C6-7) of the non-fusion group decreased significantly in some directions compared with the fusion group (p<0.05). Significant differences in the C4-6 ROM in some directions were detected between the non-fusion group and the intact group. In the fusion group, the C4-6 ROM in all directions decreased significantly compared with the intact and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some directions was negative in the non-fusion group, and a significant difference in SI-ROM was only found in the C4-6 segment of the non-fusion group compared with the fusion group. CONCLUSION: An artificial disc and vertebra system could restore vertebral height and preserve the dynamic function of the surgical area and could theoretically reduce the risk of adjacent segment degeneration compared with the anterior fusion procedure. However, our results should be considered with caution because of the low power of the study. The use of a larger ...