RESUMO
Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.
Assuntos
Doenças Autoimunes , Miosite , Autoanticorpos , Estresse do Retículo Endoplasmático/fisiologia , Humanos , Debilidade MuscularRESUMO
There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Crotonatos/uso terapêutico , Hidroxibutiratos/uso terapêutico , Leflunomida/uso terapêutico , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Estudos Transversais , Crotonatos/efeitos adversos , Crotonatos/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hidroxibutiratos/efeitos adversos , Hidroxibutiratos/sangue , Leflunomida/efeitos adversos , Leflunomida/sangue , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/sangue , Valor Preditivo dos Testes , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Toluidinas/efeitos adversos , Toluidinas/sangue , Resultado do TratamentoRESUMO
Background: individuals with type 2 diabetes show emotional distress as they learn how to cope with the disease. The emotional distress increases the possibility of complications in these patients. The aims of the present study were to evaluate the impact of the emotional distress in the quality of life of individuals with diabetes, and to investigate the demographic and clinical characteristics associated with the emotional distress of living with diabetes in a Mexican population. Methods: a total of 422 Mexican individuals with type 2 diabetes were recruited from the outpatient Diabetes Clinic of the Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa of Villahermosa, Tabasco. Demographic and clinical characteristics along with quality of life (SF-36) were assessed in these individuals. The emotional distress of living with diabetes was measured using the 5-item Problem Areas in Diabetes. Patients were divided according to the presence of high or low distress. Results: we identified that 31.8% (n = 134) of patients presented high diabetes-related emotional distress. We observed that hepatic diseases as comorbidities (p = 0.008) and diagnosis of major depression (p = 0.04) are factors associated with the emotional distress of living with diabetes. These patients showed a reduced quality of life in all dimensions (p < 0.001); the most affected dimensions were physical role (d = 0.37) and general health (d = 0.89) showing lower scores in comparison with patients with low emotional distress. Conclusions: our results suggest that Mexican individuals with type 2 diabetes mellitus show high emotional distress living with the disease and have a decreased quality of life. Therefore, it is necessary to decrease factors associated with the high emotional distress of living with diabetes in patients with type 2 diabetes.
Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Diabetes Mellitus Tipo 2/psicologia , Nível de Saúde , Angústia Psicológica , Qualidade de Vida/psicologia , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto JovemRESUMO
The DUF642 protein family is found exclusively in spermatophytes and is represented by 10 genes in Arabidopsis and in most of the 24 plant species analyzed to date. Even though the primary structure of DUF642 proteins is highly conserved in different spermatophyte species, studies of their expression patterns in Arabidopsis have shown that the spatial-temporal expression pattern for each gene is specific and consistent with the phenotypes of the mutant plants studied so far. Additionally, the regulation of DUF642 gene expression by hormones and environmental stimuli was specific for each gene, showing both up- and down-regulation depending of the analyzed tissue and the intensity or duration of the stimuli. These expression patterns suggest that the DUF642 genes are involved throughout the development and growth of plants. In general, changes in the expression patterns of DUF642 genes can be related to changes in pectin methyl esterase activity and/or to changes in the degree of methyl-esterified homogalacturonans during plant development in different cell types. Thus, the regulation of pectin methyl esterases mediated by DUF642 genes could contribute to the regulation of the cell wall properties during plant growth.
Assuntos
Parede Celular/metabolismo , Desenvolvimento Vegetal , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Desenvolvimento Vegetal/genética , Proteínas de Plantas/genéticaRESUMO
OBJECTIVE: To evaluate if an intraoperative cerebral regional oxygen saturation (crSO2) decrease, less pronounced than 20% below baseline (the current threshold believed to be associated with cognitive dysfunction in adults), is associated with negative postoperative behavioral changes (NPOBC) in the pediatric population after noncardiac surgeries. STUDY DESIGN: A prospective observational study was conducted with 198 children aged 2-12 years old scheduled for noncardiac procedures under general anesthesia. Intraoperatively, crSO2 was monitored with a cerebral oximeter. On postoperative day 7, the Post-Hospital Behavior Questionnaire was used to diagnose NPOBC. RESULTS: The incidence of NPOBC was 38.8%. Logistic regression analysis revealed that with every 1% reduction of crSO2 from the baseline value, the odds of developing NPOBC were 1.199 higher. Likewise, preoperative anxiety (OR 2.832, P = .006), duration of surgery (OR 1.026, P < .0001), and being between the ages of 2 and 3 years (OR 2.604, P = .048) were associated with NPOBC incidence. The multivariable logistic regression model receiver operating characteristic curve showed an area under the curve (95% CI) = 0.820 (0.759-0.881). CONCLUSIONS: During noncardiac surgeries in the pediatric population, an intraoperative decrease in crSO2 less pronounced than 20% from the baseline value is associated with negative postoperative behavior changes on postoperative day 7. The long-term implications remain to be determined, but this supports attention to crSO2 during noncardiac surgeries.
Assuntos
Anestesia Geral/efeitos adversos , Encéfalo/fisiopatologia , Transtornos do Comportamento Infantil/complicações , Oxigênio/metabolismo , Complicações Pós-Operatórias/diagnóstico , Fatores Etários , Circulação Cerebrovascular , Criança , Transtornos do Comportamento Infantil/diagnóstico , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Hemodinâmica , Humanos , Incidência , Masculino , Monitorização Fisiológica/métodos , Oximetria , Pediatria , Período Pós-Operatório , Estudos Prospectivos , Análise de Regressão , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Legume seed development represents a high demand for energy and metabolic resources to support the massive synthesis of starch and proteins. However, embryo growth occurs in an environment with reduced O2 that forces the plant to adapt its metabolic activities to maximize efficient energy use. SNF1-related protein kinase1 (SnRK1) is a master metabolic regulator needed for cells adaptation to conditions that reduce energy availability, and its activity is needed for the successful development of seeds. In bean embryo extracts, SnRK1 can be separated by anion exchange chromatography into two pools: one where the catalytic subunit is phosphorylated (SnRK1-p) and another with reduced phosphorylation (SnRK1-np). The phosphorylation of the catalytic subunit produces a large increase in SnRK1 activity but has a minor effect in determining its sensitivity to metabolic inhibitors such as trehalose 6-P (T6P), ADP-glucose (ADPG), glucose 1-P (G1P) and glucose 6-P (G6P). In Arabidopsis thaliana, upstream activating kinases (SnAK) phosphorylate the SnRK1 catalytic subunit at T175/176, promoting and enhancing its activity. Recombinant Phaseolus vulgaris homologous to SnAK proteins (PvSnAK), can phosphorylate and activate the catalytic domains of the α-subunits of Arabidopsis, as well as the SnRK1-np pool purified from bean embryos. While the phosphorylation process is extremely efficient for catalytic domains, the phosphorylation of the SnRK1-np complex was less effective but produced a significant increase in activity. The presence of SnRK1-np could contribute to a quick response to unexpected adverse conditions. However, in addition to PvSnAK kinases, other factors might contribute to regulating the activation of SnRK1.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Domínio Catalítico , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Phaseolus/genética , Phaseolus/metabolismo , Fosforilação/genética , Fosforilação/fisiologiaRESUMO
Objetivo: Diseñar medidas de intervención prioritarias para mantener la Salud y Seguridad de la comunidad en la Institución educativa Josefa Donado en Soledad Atlántico. Materiales y Métodos: Estudio descriptivo de corte transversal con una muestra de 535 estudiantes. Para la recolección de datos fue necesario realizar inspecciones técnicas en la institución, entrevistas al personal, revisión documental, y aplicación de los GTC 45 como instrumento. Los datos obtenidos fueron analizados estadísticamente. Resultados: Los riesgos prioritarios en la institución educativa Josefa Donado son eléctricos biomecánicos, locativos, tecnológicos, físicos y biológicos, mientras que las principales medidas de intervención consisten en la realización de reparaciones, elaboración de cronogramas de mantenimientos preventivos, estructuración de programa de pausas activas, sensibilizaciones y dotación de mobiliarios y equipos adecuados a las necesidades de los puestos de trabajo. Conclusión: La institución educativa Josefa Donado presenta un avanzado estado de deterioro en su estructura física, tal y como se verificó en las inspecciones realizadas y corroboró por noticias emitidas en medios de comunicación de alta circulación regional. Por lo anterior se concluye que las medidas de intervención propuestas deberían ser implementadas a la mayor brevedad posible para mejorar las condiciones de seguridad y salud de la comunidad educativa.
Objective: Design priority intervention measures to keep the health and security of the community in the "institución educativa Josefa Donado de Soledad". Methods and materials: Descriptive studio cross-sectional with a sample population of 535 students. For the data collection it was necessary to realize technical inspections in the institution, interview the workers, review documents and the application of the GTC 45 as an instrument. The data obtained were statistically analyzed. Results: The priority risks in the educational institution Josefa Donado are of kind electrical, biomechanical, locative, technological, physical and biological, meanwhile the principal intervention measurements are about the realization of reparations, the elaboration of chronograms of maintenance, programming active breaks, sensitization and endowment of furniture and equipment adapted to the needs of the working places. Conclusion: The educational institution Josefa Donado presents an outpost level of deterioration in his physical structure, as verified during the inspections that we made, and being confirmed by several media of the region. By the previous thing there is concluded that the intervention measurements proposed should be implemented as soon as possible, in order to improve the conditions of safety and health of the educational community.
Assuntos
Humanos , Saúde Ocupacional , Regiões do Corpo , Doenças Musculoesqueléticas , Estudos Populacionais em Saúde PúblicaRESUMO
The endosperm is a transitory structure involved in proper embryo elongation. The cell walls of mature seed endosperm are generally composed of a uniform distribution of cellulose, unesterified homogalacturonans, and arabinans. Recent studies suggest that changes in cell wall properties during endosperm development could be related to embryo growth. The degree of methyl esterification of homogalacturonans may be involved in this endosperm tissue remodelling. The relevance of the degree of homogalacturonan methyl esterification during seed development was determined by immunohistochemical analyses using a panel of probes with specificity for homogalaturonans with different degrees of methyl esterification. Low-esterified and un-esterified homogalacturonans were abundant in endosperm cells during embryo bending and were also detected in mature embryos. BIDXII (BDX) could be involved in seed development, because bdx-1 mutants had misshapen embryos. The methyl esterification pattern described for WT seeds was different during bdx-1 seed development; un-esterified homogalacturonans were scarcely present in the cell walls of endosperm in bending embryos and mature seeds. Our results suggested that the degree of methyl esterification of homogalacturonans in the endosperm cell wall may be involved in proper embryo development.
Assuntos
Arabidopsis/embriologia , Arabidopsis/fisiologia , Endosperma/embriologia , Endosperma/metabolismo , Pectinas/metabolismo , Sementes/fisiologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Desenvolvimento Embrionário/fisiologia , EsterificaçãoRESUMO
The SnRK1 complexes in plants belong to the family of AMPK/SNF1 kinases, which have been associated with the control of energy balance, in addition to being involved in the regulation of other aspects of plant growth and development. Analysis of complex formation indicates that increased activity is achieved when the catalytic subunit is phosphorylated and bound to regulatory subunits. SnRK1.1 subunit activity is higher than that of SnRK1.2, which also exhibits reduced activation due to the regulatory subunits. The catalytic phosphomimetic subunits (T175/176D) do not exhibit high activity levels, which indicate that the amino acid change does not produce the same effect as phosphorylation. Based on the mammalian AMPK X-ray structure, the plant SnRK1.1/AKINßγ-ß3 was modeled by homology modeling and Molecular Dynamics simulations (MD). The model predicted an intimate and extensive contact between a hydrophobic region of AKINßγ and the ß3 subunit. While the AKINßγ prediction retains the 4 CBS domain organization of the mammalian enzyme, significant differences are found in the putative nucleotide binding pockets. Docking and MD studies identified two sites between CBS 3 and 4 which may bind adenine nucleotides, but only one appears to be functional, as judging from the predicted binding energies. The recombinant AKINßγ-ßs complexes were found to bind adenine nucleotides with dissociation constant (Kd) in the range of the AMP low affinity site in AMPK. The saturation binding data was consistent with a one-site model, in agreement with the in silico calculations. As has been suggested previously, the effect of AMP was found to slow down dephosphorylation but did not influence activity.
Assuntos
Nucleotídeos de Adenina/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Escherichia coli/enzimologia , Modelos Estruturais , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/genética , Arabidopsis/genética , Domínio Catalítico , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Recombinantes , Fatores de Transcrição/metabolismoRESUMO
In plants, the cell wall is a complex and dynamic structure comprising high molecular weight carbohydrates and proteins. The cell wall plays an important role in several stages of the plant life cycle, including cell division, elongation and differentiation. The DUF642 family of cell wall proteins is highly conserved in spermatophytes and might be involved in pectin structural modifications. Particularly, At2g41800 is one of the most highly induced genes during the M/G1 phases of the cell cycle, and the protein encodes by this gene has been detected in cell wall proteomes of cell suspension cultures. In the present study, the expression of At2g41800 (TEB) was confirmed in primary and lateral roots, stigmatic papillae and hypocotyls. Subcellular localization studies showed that TEB is located in the cell wall. The root length and lateral root density were not affected in either of the two teb mutants studied, but the length of the hypocotyls from seedlings grown under light and dark conditions was increased. Immunogold labelling studies using JIM5 antibodies on sections of hypocotyl epidermal cells showed an important reduction of gold particles in teb mutants. The results suggested that TEB is involved in hypocotyl elongation.