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OBJECTIVES: To develop and validate an outcome measure for assessing fears in patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). METHODS: Fears were identified in a qualitative study, and reformulated as assertions with which participants could rate their agreement (on a 0-10 numeric rating scale). A cross-sectional validation study was performed including patients diagnosed with RA or axSpA. Redundant items (correlation >0.65) were excluded. Internal consistency (Cronbach's α) and factorial structure (principal component analysis) were assessed. Patients were classified into fear levels (cluster analysis). Associations between patient variables and fear levels were evaluated using multiple logistic regression. RESULTS: 672 patients were included in the validation study (432 RA, 240 axSpA); most had moderate disease activity and were prescribed biologics. The final questionnaire included 10 questions with high internal consistency (α: 0.89) and a single dimension. Mean scores (±SD) were 51.2 (±25.4) in RA and 60.5 (±22.9) in axSpA. Groups of patients with high (17.2%), moderate (41.1%) and low (41.7%) fear scores were identified. High fear scores were associated with high Arthritis Helplessness Index scores (OR 6.85, 95% CI (3.95 to 11.87)); high Hospital Anxiety and Depression Scale anxiety (OR 5.80, 95% CI (1.19 to 4.22)) and depression (OR 2.37, 95% CI (1.29 to 4.37)) scores; low education level (OR 3.48, 95% CI (1.37 to 8.83)); and high perceived disease activity (OR 2.36, 95% CI (1.10 to 5.04)). CONCLUSIONS: Overall, 17.2% of patients had high fear scores, although disease was often well controlled. High fear scores were associated with psychological distress. This questionnaire could be useful both in routine practice and clinical trials.
Assuntos
Artrite Reumatoide/psicologia , Medo/psicologia , Medidas de Resultados Relatados pelo Paciente , Psicometria/métodos , Espondilartrite/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisa Qualitativa , Inquéritos e QuestionáriosRESUMO
BACKGROUND INFORMATION: hsMOK2 (human MOK2) is a DNA-binding transcriptional repressor. For example, it represses the IRBP (interphotoreceptor retinoid-binding protein) gene by competing with the CRX (cone-rod homeobox protein) transcriptional activator for DNA binding. Previous studies have shown an interaction between hsMOK2 and nuclear lamin A/C. This interaction could be important to explain hsMOK2 ability to repress transcription. RESULTS: In the present study, we have tested whether missense pathogenic mutations of lamin A/C, which are located in the hsMOK2-binding domain, could affect the interaction with hsMOK2. We find that none of the tested mutations is able to disrupt hsMOK2 binding in vitro or in vivo. However, we observe an aberrant cellular localization of hsMOK2 into nuclear aggregates when pathogenic lamin A/C mutant proteins are expressed. CONCLUSIONS: These results indicate that pathogenic mutations in lamin A/C lead to sequestration of hsMOK2 into nuclear aggregates, which may deregulate MOK2 target genes.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Lamina Tipo A , Mutação de Sentido Incorreto , Animais , Linhagem Celular , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Humanos , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
The original version of this article was revised due to a retrospective Open Access order.
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Misinterpretation of patient beliefs may complicate shared decision-making in rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). The objective of this study was to develop a questionnaire to assess patients' beliefs about their disease and its treatment, and to identify patient characteristics associated with these beliefs. All beliefs reported by > 5% of 50 patients in a previous study were reformulated with a partnering patient organization into statements with which participants could rate their agreement on a scale of 0-10 (totally disagree to totally agree). The resulting Questionnaire for Arthritis Dialogue (QuAD) was made available to patients with RA or axSpA. A score ≥ 7 was considered a strongly held belief. Associations between patient characteristics and individual lifestyle beliefs were assessed using multiple logistic regression. The 21-item QuAD was completed by 672 patients (432 RA, 240 axSpA; mean [±SD] age 54.2 [± 14.2]; 63.7% female). The most widely held beliefs were related to uncertainty about progression (n = 354, 54.0%), heredity (n = 309, 47.8%), and flare triggers (n = 283, 42.7%). The unwarranted belief that physical activity is deleterious to disease activity was associated with markers of psychological distress and lower educational levels. The beliefs of patients with RA or axSpA about their disease are wide-ranging. Since these may be unwarranted and may lead to inappropriate behaviors, physicians should discuss these beliefs with their patients. The QuAD may facilitate this dialogue, and may also be useful in population studies to standardize the assessment and evolution of beliefs over time. People with long-term inflammatory conditions such as rheumatoid arthritis (RA; inflammation of the joints) and axial spondyloarthritis (axSpA; inflammation of the spine) may hold a number of beliefs about their disease, including some that are not supported by current scientific evidence (e.g., "I think that my disease was triggered by a vaccination"). Some beliefs, especially those relating to the role of lifestyle factors (such as exercise, diet, smoking, and drinking alcohol), may encourage people living with severe diseases to change their behavior in a way that has an effect on their disease. Within this project, we developed a questionnaire to identify the most common beliefs held by people living with RA or axSpA, which is called the "Questionnaire for Arthritis Dialogue (QuAD)." We also examined whether certain characteristics (or traits) of people living with RA or axSpA are linked to beliefs not currently supported by scientific evidence. A total of 672 people living with RA or axSpA in France were asked to complete the questionnaire (QuAD). The questionnaire included 21 opinion statements that they scored from 0 (totally disagree) to 10 (totally agree). A score of more than 7 was interpreted to mean that the person significantly agreed with the opinion. Based on the responses to specific opinion statements in the questionnaire, we were able to identify possible links between beliefs that are not supported by scientific evidence (e.g., "I think that flare-ups of my disease are triggered by physical effort"), and characteristics of people living with severe diseases. Our findings suggested that beliefs about lifestyle and inflammatory diseases varied from person to person, were sometimes inconsistent (the most widely held beliefs were sometimes contradictory), and were often not supported by scientific evidence. The belief that physical activity had negative effects on the disease was linked to poor education and psychological issues (such as anxiety and helplessness). People living with axSpA were more likely to believe their disease was a result of their genetic make-up, whereas those with RA more often believed their disease was caused by emotional issues. People living with axSpA were also more likely to believe that physical activity could be beneficial for their disease, and less likely to believe that their disease was caused by smoking. Our results suggest that doctors need to discuss with their patients how they might believe lifestyle is associated with their disease. This will help to dispel any unnecessary concerns, and to encourage their patients to take up healthy lifestyles and habits that are beneficial for their disease management. It may also be beneficial for health care providers to discuss the beliefs identified in this study during educational programs about inflammatory diseases, for the benefit of people living with RA or axSpA.
Assuntos
Artrite Reumatoide/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Espondilartrite/psicologia , Ansiedade , Artrite Reumatoide/tratamento farmacológico , Feminino , França , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The human and murine MOK2 proteins are factors able to recognize both DNA and RNA through their zinc finger motifs. This dual affinity of MOK2 suggests that MOK2 might be involved in transcription and post-transcriptional regulation of MOK2 target genes. The IRBP gene contains two MOK2-binding elements, a complete 18 bp MOK2-binding site located in intron 2 and the essential core MOK2-binding site (8 bp of conserved 3'-half-site) located in the IRBP promoter. We have demonstrated that MOK2 can bind to the 8 bp present in the IRBP promoter and repress transcription from this promoter by competing with the CRX activator for DNA binding. In this study, we identify a novel interaction between lamin A/C and hsMOK2 by using the yeast two-hybrid system. The interaction, which was confirmed by GST pull-down assays and co-immunolocalization studies in vivo, requires the N-terminal acidic domain of hsMOK2 and the coiled 2 domain of lamin A/C. Furthermore, we show that a fraction of hsMOK2 protein is associated with the nuclear matrix. We therefore suggest that hsMOK2 interactions with lamin A/C and the nuclear matrix may be important for its ability to repress transcription.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Lamina Tipo A/metabolismo , Fatores de Transcrição/metabolismo , Sítios de Ligação , Núcleo Celular/química , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Células HeLa , Humanos , Lamina Tipo A/química , Lamina Tipo A/genética , Matriz Nuclear/química , Matriz Nuclear/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Transporte Proteico , Fatores de Transcrição/química , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
OBJECTIVES: To explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis. METHODS: 25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants' homes. The interviews were recorded and the main themes identified by content analysis. RESULTS: Patients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations. CONCLUSIONS: Patients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases.