RESUMO
PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.
Assuntos
Artrite Reumatoide/complicações , Educação a Distância/métodos , Fadiga/etiologia , Entrevista Psicológica/métodos , Artrite Reumatoide/patologia , Fadiga/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Hepatitis B virus X protein (HBX) has been implicated in the transactivation of diverse cellular genes and possibly also the pathogenesis of human hepatocellular carcinoma (HCC). We report the characterization of HBX variants from HBV-related human hepatocellular carcinoma (HCC). These HBX variants were integrated into the host chromosomes and also expressed in the HCC tissues. In addition, we report a novel in vitro HBX activity assay based on color changes that were indicative of the beta-galactosidase enzyme activity. Conducted in wheat germ lysates, the transactivating function of either wild type or mutant HBX protein was measured through their interaction with the Early Growth Response factor 1 (Egr-1) that controls the beta-galactosidase gene. Further analysis of these HBX deletion mutants using this assay may shed new insights on the significance of various mutations occurring in HCC-associated HBX.
Assuntos
Carcinoma Hepatocelular/virologia , Regulação Viral da Expressão Gênica , Variação Genética/genética , Vírus da Hepatite B/genética , Proteínas Imediatamente Precoces , Neoplasias Hepáticas/virologia , Transativadores/genética , Integração Viral , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Carcinoma Hepatocelular/genética , Extratos Celulares , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Proteína 1 de Resposta de Crescimento Precoce , Genes Reporter/genética , Vírus da Hepatite B/fisiologia , Humanos , Neoplasias Hepáticas/genética , Dados de Sequência Molecular , Mutação/genética , Biossíntese de Proteínas , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Transativadores/biossíntese , Transativadores/química , Transativadores/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ativação Transcricional , Células Tumorais Cultivadas , Proteínas Virais Reguladoras e AcessóriasRESUMO
Lamivudine is a new antiviral agent effective against hepatitis B viral (HBV) infections but can result in virus-drug resistance associated with mutations in the conserved 'YM552DD' motif of the HBV DNA polymerase. Due to their overlapping coding regions in the HBV genome, mutations in the DNA polymerase may result in substitutions in the hepatitis B surface antigen (HBsAg), albeit outside the antigenic 'a' epitope. Here we report the identification of a novel type of lamivudine-related mutations located in both the polymerase (YM552DD-->Y1552DD) and the 'a' epitope of HBsAg (Gly130-->Asp130). The same virus carried a HBsAg Gly145-->Arg145 mutation prior to therapy. Both the wild type HBV and lamivudine-related mutants with the Gly145-->Arg145 HBsAg mutation were suppressed following ganciclovir treatment, indicating a beneficial additive effect of both drugs against different forms of HBV mutants.
Assuntos
Antivirais/farmacologia , Ganciclovir/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B/virologia , Lamivudina/farmacologia , Adulto , Sequência de Aminoácidos , Antivirais/uso terapêutico , DNA Viral/análise , DNA Polimerase Dirigida por DNA/genética , Resistência Microbiana a Medicamentos/genética , Quimioterapia Combinada , Epitopos , Ganciclovir/uso terapêutico , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/genética , Humanos , Lamivudina/uso terapêutico , Masculino , Dados de Sequência Molecular , MutaçãoRESUMO
Vaccine escape hepatitis B virus surface antigen (HBsAg) mutants are capable of independent replication and have been implicated in acute hepatitis. We now report the detection of these mutants with changes at various positions of the antigenic 'a' determinant in human hepatocellular carcinoma (HCC). Southern blot analysis indicated that the HBsAg mutant with the Glycine to Arginine change at position 145 was integrated in HCC, whereas those with a Threonine at position 133 instead of a Methionine were identified in the serum of aggressive HCC. Further studies on HBsAg mutants in HCC should provide new insights on their involvement in the hepatocarcinogenesis.
