Material Engagement Shaping Participation of Children on the Autism Spectrum: Embodiment and Subjectivity in Small-Group Learning.

This study investigated the material engagement and their affordances for participation of children on the autism spectrum (AS) in small-group learning. Framed by a methodology called Idea Diary that fosters social interactions in classroom environments, our focus was on understanding how and when the construction and manipulation of the diary supported children's participation and knowledge construction in small groups. This investigation was guided by the intersection of the theory of subjectivity developed by Fernando González Rey and enactive accounts of cognition. This framework provided the view of the singularity in the communicative process of children on the AS and the necessary support for examining the mechanisms of engagement that led to children's participation. We present two case studies of 9-10-year-old boys. Data consists of the diaries produced and used by children and video recordings of children's interactions during small-group discussions. Our analytical approach included a qualitative semiotic analysis of the materials and a micro-analysis of the social interactions. The results showed, first, that children on the AS continuously engaged in the construction of the diary, expressing elements of their subjectivity-experiences, ideas and the system through which they interact with the world. Repetition framed children's productions and signalled engagement. Second, material engagement enabled participatory sense-making, which in this study appeared in creating new communicative resources between the child on the AS and their peers and in adapting the narratives, approximating children's perspectives in conversations. Although contextualised within a specific pedagogical practice, the study contributes to advancing our understanding of the role of material engagement in social participation in learning situations involving children on the AS, particularly relevant in educational psychology and education.

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Tumor Tissue Oxidative Stress Changes and Na, K-ATPase Evaluation in Head and Neck Squamous Cell Carcinoma.

Changes in metabolism are mechanisms that are largely implicated in the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC) and also in resistance to different anticancer therapies. Identification of biomarkers for differentiation between cancerous and normal epithelium, treatment design and prognosis remain a vital issue in the field of head and neck cancer. The present study analyzed the main biochemical changes that occur in HNSCC tumors by through mechanisms involving oxidative stress. The release of substances reactive to thiobarbituric acid was significantly lower in HNSCC tumor tissue as compared to healthy tissue. The assays related to the lipid profile assays showed changes in membrane biophysics of tumor cells due to an increase in total phospholipids and total cholesterol, as well as an increased activity and expression of the α1 subunit of Na, K-ATPase, which is fundamental in the process of carcinogenesis. The modulation of the antioxidant system was also affected, with a decrease in the catalytic activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as a reduction of glutathione (GSH) content and an increase in H2O2 content. A reduction in catalase (CAT) activity was observed. The data presented here are in accordance with important findings described by us in a previous study, involving the same individuals, but with a focus on the damage generated in red blood cells, resulting from tumor installation. Therefore, it was possible to conclude that the biochemical alterations found in HNSCC cells are fundamental for transformation and maintenance of the tumor cell and once it is installed, it is also capable of generating injuries in the patients' red blood cells. Our data demonstrate that this could be a promising biomarker for HNSCC.

Evaluation of the Erythrocyte Membrane in Head and Neck Cancer Patients.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and complex disease, both from a clinical and molecular point of view. The prolonged use of alcohol and tobacco, along with the release of tumor secretions can modulate blood cells, such as erythrocytes. Here, this study was conducted with 24 patients diagnosed with HNSCC and an equal number of healthy individuals are matched by age and gender. The levels of lipid peroxidation were measured using the individual plasma, while for lipid concentrations, identification and quantification Na, K-ATPase activity and osmotic fragility, the red blood cell concentrate were used. The release of TBARS was significantly higher in patients with HNSCC. The lipid profile assays demonstrated a rearrangement of the erythrocyte membrane due to a decrease in total phospholipids and phosphatidylethanolamine followed by an increase in total cholesterol and phosphatidylcholine. Na, K-ATPase activity also increased. Erythrocytes were more fragile in patients with HNSCC than in health individuals. Therefore, the membrane of erythrocytes were rearranged and Na, K-ATPase function altered in the HNSCC patients. Our findings suggests that the alcohol, tobacco and tumor secretion modulate in a specific manner that the erythrocytes membranes of these patients making this system a potential tool for HNSCC biomarker of tumor progression.

Three-dimensional comparison of the skeletal and dentoalveolar effects of the Herbst and Pendulum appliances followed by fixed appliances: A CBCT study.

OBJECTIVES: To compare three-dimensional (3D) skeletal and dentoalveolar effects of the Herbst and Pendulum appliances followed by fixed orthodontic treatment in growing patients. SETTING AND SAMPLE POPULATION: A sample of 35 adolescents with cone-beam computed tomography scans obtained prior to Herbst and Pendulum treatment (T1) and immediately after fixed appliance treatment (T2). MATERIALS AND METHODS: Patients with Class II malocclusion was assessed retrospectively and divided into two treatment groups: Herbst group (n = 17, age: 12.0 ± 1.6 years) and Pendulum group (n = 18, age: 12.1 ± 1.5 years), with a mean treatment duration of 2.8 ± 0.8 years and 2.5 ± 0.7 years, respectively. Reconstructions of the maxillomandibular and dentoalveolar regions and data in 3D were obtained relative to cranial base, maxillary and mandibular regional superimpositions. Treatment outcomes (T2-T1) were compared between both groups using t tests for independent samples (P<.05). RESULTS: Significant increase in mandibular length was observed in the Herbst group (7.3 ± 3.5 mm) relative to the Pendulum group (4.6 ± 4.5 mm). Inferior and anterior displacements of Pogonion were 2.2 mm and 1.6 mm greater in the Herbst group, respectively. The mesial displacement of the lower first molars was significantly greater in the Herbst group (1.9 mm). The upper first molars had contrasting results in sagittal displacement, with 0.6 ± 1.7 mm of distal displacement with the Pendulum and 1.4 ± 2.1 mm of mesial displacement with the Herbst. Lower incisor projection and proclination were similar between groups. CONCLUSIONS: The Herbst and Pendulum appliances followed by comprehensive orthodontic treatment effectively corrected Class II malocclusion in growing patients, but with differing skeletal and dentoalveolar effects.

Reduced CD8+ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions.

OBJECTIVE: The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC). MATERIALS AND METHODS: Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed. RESULTS: Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4+ cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8+ cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8+ cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027). CONCLUSIONS: CD8+ cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8+ cells than its associated OPML. CLINICAL RELEVANCE: Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.

Three-dimensional treatment outcomes in Class II patients with different vertical facial patterns treated with the Herbst appliance.

INTRODUCTION: The aims of this study were to evaluate, using 3-dimensional superimposition techniques, the skeletal changes in Class II subjects with different vertical facial patterns treated with the Herbst appliance and to compare these skeletal changes to those of Class II controls treated with elastics. METHODS: Sixteen Herbst patients who met the inclusion criteria were divided into 2 equal groups based on vertical facial pattern as determined by the Frankfort mandibular plane angle (brachyfacial, ≤22°; mesofacial, 23°-29°) and had cone-beam computed tomographs taken before treatment, 8 weeks after Herbst appliance removal, and after subsequent fixed appliance treatment. Eleven Class II control patients treated with fixed appliances and elastics had cone-beam computed tomographs taken before and after treatment. Three-dimensional models were generated from the cone-beam computed tomography images, registered on the anterior cranial bases, and analyzed using color maps and point-to-point measurements. RESULTS: There were minimal differences in treatment response between the 2 Herbst groups across all skeletal parameters measured. The Herbst subjects showed a greater inferior displacement of anterior nasal spine compared with the Class II controls (Herbst brachyfacial, -1.44 mm; Herbst mesofacial, -1.95 mm) with other maxillary changes being clinically insignificant. The Herbst subjects showed greater inferior displacement of B-point compared with the Class II controls (Herbst brachyfacial, -2.59 mm; Herbst mesofacial, -2.75 mm). There were no statistically significant differences in mean linear mandibular measurements. All groups showed a trend toward posterior displacement of the condyles and glenoid fossae from the start to the end of treatment, with no significant differences across the 3 groups. There were minimal differences in the changes in gonial angle and Frankfort mandibular plane angle across all groups. CONCLUSION: Approximately 2 years after Herbst treatment, the Herbst subjects with different vertical facial patterns showed similar patterns of skeletal change compared with the Class II controls treated with elastics.

A web-based system for neural network based classification in temporomandibular joint osteoarthritis.

OBJECTIVE: The purpose of this study is to describe the methodological innovations of a web-based system for storage, integration and computation of biomedical data, using a training imaging dataset to remotely compute a deep neural network classifier of temporomandibular joint osteoarthritis (TMJOA). METHODS: This study imaging dataset consisted of three-dimensional (3D) surface meshes of mandibular condyles constructed from cone beam computed tomography (CBCT) scans. The training dataset consisted of 259 condyles, 105 from control subjects and 154 from patients with diagnosis of TMJ OA. For the image analysis classification, 34 right and left condyles from 17 patients (39.9 ±â€¯11.7 years), who experienced signs and symptoms of the disease for less than 5 years, were included as the testing dataset. For the integrative statistical model of clinical, biological and imaging markers, the sample consisted of the same 17 test OA subjects and 17 age and sex matched control subjects (39.4 ±â€¯15.4 years), who did not show any sign or symptom of OA. For these 34 subjects, a standardized clinical questionnaire, blood and saliva samples were also collected. The technological methodologies in this study include a deep neural network classifier of 3D condylar morphology (ShapeVariationAnalyzer, SVA), and a flexible web-based system for data storage, computation and integration (DSCI) of high dimensional imaging, clinical, and biological data. RESULTS: The DSCI system trained and tested the neural network, indicating 5 stages of structural degenerative changes in condylar morphology in the TMJ with 91% close agreement between the clinician consensus and the SVA classifier. The DSCI remotely ran with a novel application of a statistical analysis, the Multivariate Functional Shape Data Analysis, that computed high dimensional correlations between shape 3D coordinates, clinical pain levels and levels of biological markers, and then graphically displayed the computation results. CONCLUSIONS: The findings of this study demonstrate a comprehensive phenotypic characterization of TMJ health and disease at clinical, imaging and biological levels, using novel flexible and versatile open-source tools for a web-based system that provides advanced shape statistical analysis and a neural network based classification of temporomandibular joint osteoarthritis.

The 17D-204 and 17DD yellow fever vaccines: an overview of major similarities and subtle differences.

INTRODUCTION: The yellow fever vaccine is a live attenuated virus vaccine that is considered one of the most efficient vaccines produced to date. The original 17D strain generated the substrains 17D-204 and 17DD, which are used for the current production of vaccines against yellow fever. The 17D-204 and 17DD substrains present subtle differences in their nucleotide compositions, which can potentially lead to variations in immunogenicity and reactogenicity. We will address the main changes in the immune responses induced by the 17D-204 and 17DD yellow fever vaccines and report similarities and differences between these vaccines in cellular and humoral immunity . This is a relevant issue in view of the re-emergence of yellow fever in Uganda in 2016 and in Brazil in the beginning of 2017. AREAS COVERED: This article will be divided into 8 sections that will analyze the innate immune response, adaptive immune response, humoral response, production of cytokines, immunity in children, immunity in the elderly, gene expression and adverse reactions. EXPERT COMMENTARY: The 17D-204 and 17DD yellow fever vaccines present similar immunogenicity, with strong activation of the cellular and humoral immune responses. Additionally, both vaccines have similar adverse effects, which are mostly mild and thus are considered safe.

Measuring fatigue with multiple instruments in a Brazilian cohort of early rheumatoid arthritis patients / Mensuração da fadiga com múltiplos instrumentos em uma coorte brasileira de pacientes com artrite reumatoide em fase inicial

Abstract Objective: To assess the prevalence of fatigue in a Brazilian population with early rheumatoid arthritis using multiple instruments, and the predictors of these instruments by differents independent variables. Methods: Cross-sectional study with direct interview and medical records review. Fatigue, dependent variable, was assessed using eight instruments: Profile of Mood States (POMS), Multidimensional Assessment of Fatigue scale (MAF), Fatigue Severity Scale (FSS), Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), Numerical Rating Scales (BRAF-NRS), Short-form Survey 36 (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Visual Analogic Scale for Fatigue (VASf). Independent variables: sociodemographic, clinical and serological, were measured using medical records and direct interview. Disability and disease activity were assessed using the Health Assessment Questionnaire (HAQ) and disease activity assessed using the Disease Activity Score 28 joints (DAS28). The scores of scales demonstrated the level of fatigue and multiple linear regression method used in statistical analysis to demonstrate prediction models. Results: A total of 80 patients was assessed, and 57 reported clinically relevant fatigue (VASf > 2), representing 71.25% prevalence point (51 women [89.5%], mean age 48.35 ± 15 years, and mean disease duration of 4.92 ± 3.8 years). Eight predictive models showed statistical significance, one for each fatigue instrument. The highest coefficient of determination (R 2) was 56% for SF-36 and the lowest (R 2 = 21%) for FSS. The HAQ was the only independent variable to predict fatigue on all instruments. Conclusion: Clinically relevant fatigue is a highly prevalent symptom and is mostly predicted by disability and age in the population assessed.

Resumo Objetivo: Avaliar a prevalência de fadiga em uma coorte brasileira de pacientes com artrite reumatoide em fase inicial com múltiplos instrumentos e os preditores desses instrumentos de acordo com diferentes variáveis independentes. Métodos: Estudo transversal com entrevista direta e revisão de prontuários. A fadiga, a variável dependente, foi avaliada por meio de oito instrumentos: Profile of Mood States (POMS), Multidimensional Assessment of Fatigue Scale (MAF), Fatigue Severity Scale (FSS), Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), Numerical Rating Scales (BRAF-NRS), Short-form Survey 36 (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (Facit-F) e Escala Visual Analógica de fadiga (VASf). Variáveis independentes: mensuraram-se dados sociodemográficos, clínicos e sorológicos por meio da análise de prontuários e entrevista direta. A incapacidade e a atividade da doença foram avaliadas com o Health Assessment Questionnaire (HAQ). A atividade da doença foi avaliada com o Disease Activity Score 28 joints (DAS-28). As pontuações das escalas mostraram o nível de fadiga e usou-se o método de regressão linear múltipla na análise estatística para demonstrar os modelos de predição. Resultados: Avaliaram-se 80 pacientes; 57 relataram fadiga clinicamente relevante (VASf > 2), representaram uma prevalência de 71,25% (51 mulheres [89,5%], média de 48,35 ± 15 anos e duração média da doença de 4,92 ± 3,8 anos). Oito modelos preditivos mostraram significância estatística, um para cada instrumento de fadiga. O maior coeficiente de determinação (R2) foi de 56% para o SF-36 e o menor (R2 = 21%) foi para a FSS. O HAQ foi a única variável independente que predisse a fadiga em todos os instrumentos. Conclusão: A fadiga clinicamente relevante é um sintoma altamente prevalente e é principalmente predita pela incapacidade e idade na população avaliada.

Measuring fatigue with multiple instruments in a Brazilian cohort of early rheumatoid arthritis patients.

OBJECTIVE: To assess the prevalence of fatigue in a Brazilian population with early rheumatoid arthritis using multiple instruments, and the predictors of these instruments by differents independent variables. METHODS: Cross-sectional study with direct interview and medical records review. Fatigue, dependent variable, was assessed using eight instruments: Profile of Mood States (POMS), Multidimensional Assessment of Fatigue scale (MAF), Fatigue Severity Scale (FSS), Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), Numerical Rating Scales (BRAF-NRS), Short-form Survey 36 (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Visual Analogic Scale for Fatigue (VASf). INDEPENDENT VARIABLES: sociodemographic, clinical and serological, were measured using medical records and direct interview. Disability and disease activity were assessed using the Health Assessment Questionnaire (HAQ) and disease activity assessed using the Disease Activity Score 28 joints (DAS28). The scores of scales demonstrated the level of fatigue and multiple linear regression method used in statistical analysis to demonstrate prediction models. RESULTS: A total of 80 patients was assessed, and 57 reported clinically relevant fatigue (VASf>2), representing 71.25% prevalence point (51 women [89.5%], mean age 48.35±15 years, and mean disease duration of 4.92±3.8 years). Eight predictive models showed statistical significance, one for each fatigue instrument. The highest coefficient of determination (R2) was 56% for SF-36 and the lowest (R2=21%) for FSS. The HAQ was the only independent variable to predict fatigue on all instruments. CONCLUSION: Clinically relevant fatigue is a highly prevalent symptom and is mostly predicted by disability and age in the population assessed.

Federating Heterogeneous Datasets to Enhance Data Sharing and Experiment Reproducibility.

Recent studies have demonstrated the difficulties to replicate scientific findings and/or experiments published in past.1 The effects seen in the replicated experiments were smaller than previously reported. Some of the explanations for these findings include the complexity of the experimental design and the pressure on researches to report positive findings. The International Committee of Medical Journal Editors (ICMJE) suggests that every study considered for publication must submit a plan to share the de-identified patient data no later than 6 months after publication. There is a growing demand to enhance the management of clinical data, facilitate data sharing across institutions and also to keep track of the data from previous experiments. The ultimate goal is to assure the reproducibility of experiments in the future. This paper describes Shiny-tooth, a web based application created to improve clinical data acquisition during the clinical trial; data federation of such data as well as morphological data derived from medical images; Currently, this application is being used to store clinical data from an osteoarthritis (OA) study. This work is submitted to the SPIE Biomedical Applications in Molecular, Structural, and Functional Imaging conference.

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.

Elaboração de ação educativa sobre câncer de boca para escolares em Divinópolis, Minas Gerais: um relato de experiência / Elaboration of educational action on oral cancer for students in Divinópolis, Minas Gerais: an experience report

A ação educativa é essencial para consolidar a promoção de saúde na Atenção Primária e tem grande potencial para melhorar os índices de saúde da população, desde que planejada, elaborada e executada segundo referencial teórico consistente. Este relato de experiência descreve todo o processo de elaboração de uma ação educativa sobre câncer de boca direcionada a escolares do 7º ao 9º ano do ensino fundamental das escolas municipais de Divinópolis, Minas Gerais. Os resultados deste estudo mostraram que cada fase − planejamento, revisão de literatura, estudo-piloto com realização de pré-teste e pós-teste − foi essencial para garantir a qualidade da fase subsequente e, por conseguinte, da ação como um todo.

The educational action is essential to consolidate the health promotion in the primary care, and has great potential to improve the health indexes of the population, provided that be planned, elaborated and implemented according consistent theoretical approach. The experience report is used to describe the entire process of developing of an oral cancer educational action targeted at students from 7º to 9º year of basic education from Divinópolis, city in the state of Minas Gerais. The results of the study show that each stage ­ planning, literature review, pilot study and pre-test and post-test administered ­ was essential to ensure the quality of the subsequent stage, therefore for the action as a whole.

Effect of the Chronic Use of Lithium Carbonate on Induced Tooth Movement in Wistar Rats.

Patients who seek dental treatment may have bipolar disorder, and lithium carbonate (LC) is the drug of choice used in the treatment of this disorder. Taking into consideration the controversial results found in the literature, and the possible influence of LC on induced tooth movement, the objective was to evaluate tooth movement induced in rats after administration of lithium carbonate. One hundred and ninety-two rats were divided into 3 groups. In the L group, the animals received daily 60mg/kg of LC, they were not subjected to orthodontic movement, and they were euthanized after 33, 37, 44 or 51 days. In the LM group, the LC was administered for 30 days and during the subsequent 3, 7, 14 and 21 days, corresponding to the period of induced tooth movement, and they received a spring that produced a 30cN force. In the SM group, saline solution was applied. Measurements were made of tooth displacement, the numbers of osteoclasts and serum lithium phosphate (PO4), alkaline phosphatase (ALP) and creatinine levels. The tooth displacement was lower in the LM group compared to the SM group at 44 days. A tendency toward reduction in the number of osteoclasts was observed in the LM group compared to the SM group at 44 days. The average lithium were higher in the L and LM groups compared to the SM group. The opposite was observed for the PO4 group. A higher value for the ALP was found in the L group. The average creatinine level was lower in the LM group. LC inhibited tooth movement for 14 days, possibly due to the reduction in the number of osteoclasts.

Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells.

Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated RNA. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncRNAs functions as immunostimulatory "self-agonists" and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncRNAs arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncRNAs expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncRNA expression in cancers and their relationship to the tumor microenvironment.

Como o reumatologista pode orientar o paciente com artrite reumatoide sobre função sexual / How the rheumatologist can guide the patient with rheumatoid arthritis on sexual function

RESUMOA sexualidade, parte integrante da vida humana e da qualidade de vida, é uma das responsáveis pelo bem-estar individual. A disfunção sexual pode ser definida como alteração em algum componente da atividade sexual e pode acarretar frustração, dor e diminuição dos intercursos sexuais. Embora se saiba que doenças crônicas, como a artrite reumatoide (AR), influenciam a qualidade da vida sexual, a disfunção sexual ainda é pouco diagnosticada, o que se deve a dois motivos: tanto os pacientes deixam de relatar a queixa por vergonha ou frustração quanto os médicos pouco questionam seus pacientes a esse respeito. Os reumatologistas estão cada vez mais dispostos a discutir domínios que não estão diretamente relacionados com o tratamento medicamentoso das doenças articulares, como qualidade de vida, fadiga e educação dos pacientes. A sexualidade, no entanto, é muito pouco abordada. O objetivo desta revisão é apresentar alguns conceitos úteis ao reumatologista para orientação do paciente com AR quanto à função/disfunção sexual, considerações relativas ao papel desse profissional no sentido de instruir o paciente, noções gerais sobre função sexual, incluindo conceitos práticos sobre posições sexuais mais adequadas para portadores de AR, e abordagem multidisciplinar da disfunção sexual.

ABSTRACTSexuality, an integral part of human life and quality of life, is one of those factors responsible for individual welfare. Sexual dysfunction can be defined as a change in any component of sexual activity, which may cause frustration, pain and decreased sexual intercourse. Although it is known that chronic diseases, such as rheumatoid arthritis (RA), influence the quality of sexual life, sexual dysfunction is still underdiagnosed, due to two reasons: (i) patients fail to report the complaint because of shame or frustration and (ii) this subject is rarely called into question by doctors. Rheumatologists are increasingly willing to discuss areas which are not directly related to drug treatment of joint diseases, such as quality of life, fatigue, and education of patients; however, sexuality is rarely addressed. The aim of this review is to present some useful concepts to Rheumatologists for orientation of their patients with RA with respect to sexual function/dysfunction, some considerations concerning the role of these professionals in order to instruct the patient, general notions about sexual function, including practical concepts about the more appropriate sexual positions for patients with RA, and a multidisciplinary approach to sexual dysfunction.

Terapia ocupacional na artrite reumatoide: o que o reumatologista precisa saber? / Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?

Intervenções voltadas para a educação e o autogerenciamento da artrite reumatoide (AR) pelo paciente aumentam a adesão e a eficácia da abordagem precoce. A combinação de tratamento medicamentoso e tratamento de reabilitação visa a potencializar as possibilidades de intervenção, retardar o aparecimento de novos sintomas, reduzir incapacidades, minimizar sequelas e reduzir o impacto dos sintomas sobre a funcionalidade do paciente. A terapia ocupacional é uma profissão da área da saúde que objetiva a melhoria do desempenho de atividades pelo paciente e fornece meios para a prevenção de limitações funcionais, adaptação a modificações no cotidiano e manutenção ou melhoria de seu estado emocional e participação social. Devido ao caráter sistêmico da AR o acompanhamento multidisciplinar é necessário para o adequado manejo do impacto da doença sobre os mais diversos aspetos da vida do paciente. Como membro da equipe de saúde, o terapeuta ocupacional objetiva a melhoria e manutenção da capacidade funcional do paciente, prevenir o agravamento de deformidades, auxiliar o processo de compreensão e enfrentamento da doença, fornecer meios para as atividades necessárias para o engajamento do indivíduo em ocupações significativas, favorecer sua autonomia e independência em atividades de autocuidado, laborais, educacionais, sociais e de lazer. O objetivo desta revisão é familiarizar o reumatologista com as ferramentas de avaliação e intervenção usadas na terapia ocupacional, com enfoque na aplicação desses princípios para o tratamento de pacientes com diagnóstico de AR.

Interventions focusing on education and self-management of rheumatoid arthritis (RA) by the patient improves adherence and effectiveness of early treatment. The combination of pharmacologic and rehabilitation treatment aims to maximize the possibilities of intervention, delaying the appearance of new symptoms, reducing disability and minimizing sequelae, decreasing the impact of symptoms on patient's functionality. Occupational therapy is a health profession that aims to improve the performance of daily activities by the patient, providing means for the prevention of functional limitations, adaptation to lifestyle changes and maintenance or improvement of psychosocial health. Due to the systemic nature of RA, multidisciplinary follow-up is necessary for the proper management of the impact of the disease on various aspects of life. As a member of the health team, occupational therapists objective to improve and maintaining functional capacity of the patient, preventing the progression of deformities, assisting the process of understanding and coping with the disease and providing means for carrying out the activities required for the engagement of the individual in meaningful occupations, favoring autonomy and independence in self-care activities, employment, educational, social and leisure. The objective of this review is to familiarize the rheumatologist with the tools used for assessment and intervention in occupational therapy, focusing on the application of these principles to the treatment of patients with RA.

Impact of Therapy on Metabolic Syndrome in Young Adult Premenopausal Female Lupus Patients: Beneficial Effect of Antimalarials.

OBJECTIVE: There are no data about the main factors associated with metabolic syndrome in young premenopausal systemic lupus erythematosus (SLE) patients. The aim of the study was to evaluate the frequency of metabolic syndrome and disease- or therapy-related factors in premenopausal young SLE patients. METHODS: A total of 103 premenopausal SLE patients ages <40 years were selected and compared to 35 healthy premenopausal age-matched women. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. RESULTS: A higher frequency of metabolic syndrome (22.3% versus 5.7%; P = 0.03) was observed in the SLE group. Metabolic syndrome-SLE patients had higher SLE Disease Activity Index scores (mean ± SD 5.9 ± 7.6 versus 1.9 ± 2.7; P = 0.006), more frequently had previous renal disease (73.9% versus 51.2%; P = 0.05) and current renal disease (34.8% versus 10.0%; P = 0.008), and had higher current prednisone dose (median [range] 20 [0-60] versus 5 [0-60] mg/dl; P = 0.018) and cumulative prednisone dose (mean ± SD 41.48 ± 27.81 versus 24.7 ± 18.66 gm; P = 0.023) than those without metabolic syndrome. Chloroquine was less frequently used in metabolic syndrome-SLE patients (65.2% versus 90.0%; P = 0.008). In multivariate analysis, only current chloroquine use (prevalence ratio [PR] 0.29, 95% confidence interval [95% CI] 0.13-0.64) and cumulative prednisone were associated with metabolic syndrome (PR 1.02, 95% CI 1.01-1.04). Further estimated prevalence analysis identified the fact that antimalarial use promoted continuous decrease in the progressive metabolic syndrome prevalence associated with glucocorticoid cumulative dose. CONCLUSION: The prevalence of metabolic syndrome is high in premenopausal young adult SLE patients. Chloroquine has a protective effect on the prevalence of metabolic syndrome in these patients, and this benefit counteracts the deleterious effect of glucocorticoids in a dose-dependent manner.

Prevalência de disfunção sexual entre pacientes acompanhadas na coorte Brasília de artrite reumatoide inicial / Prevalence of sexual dysfunction among female patients followed in a Brasília Cohort of early rheumatoid arthritis

Objetivo: Determinar a prevalência de disfunção sexual em mulheres com diagnóstico de artrite reumatoide (AR) inicial (menos de um ano de sintomas ao diagnóstico), bem como avaliar a possível associação entre disfunção sexual com atividade da AR e incapacidade funcional. Métodos: Estudo transversal, que avaliou mulheres com diagnóstico de AR inicial, acompanhadas de forma protocolar na coorte Brasília, no Hospital Universitário de Brasília. Dados demográficos, índice de atividade da doença (Disease Activity Score 28 – DAS 28) e dados do questionário de incapacidade funcional (Health Assessment Questionnaire – HAQ) foram obtidos por entrevistas diretas. Usou-se o índice de função sexual feminina (Female Sexual Function Index – FSFI), questionário que contém 19 itens que avaliam seis domínios: desejo sexual, excitação sexual, lubrificação vaginal, orgasmo, satisfação sexual e dor. Resultados: Foram estudadas 68 pacientes, das quais 54 (79,4%) relataram atividade sexual nas últimas quatro semanas. A média de idade foi de 49,7 ± 13,7 anos e a maioria era casada (61,4%). O DAS-28 médio foi de 3,6 ± 1,5 e a média do HAQ foi de 0,7. A prevalência de disfunção sexual (FSFI ≤26) foi de 79,6%. Não houve associação de atividade de doença nem de incapacidade funcional com a ocorrência de disfunção sexual nas pacientes avaliadas. Conclusão: A prevalência de disfunção sexual encontrada neste estudo foi superior à relatado na literatura em mulheres saudáveis. Há necessidade de conhecimento da extensão do problema para oferecer possibilidades terapêuticas adequadas aos pacientes. .

Objective: To determine the prevalence of sexual dysfunction in women diagnosed with early rheumatoid arthritis (RA) (less than one year of symptoms at the time of diagnosis), as well as to evaluate the possible association between sexual dysfunction with AR activity and functional disability. Methods: Cross-sectional study assessing women diagnosed with early RA, accompanied per protocol in the Brasilia Cohort, Hospital Universitário de Brasília. Demographics, disease activity index (Disease Activity Score 28 – DAS 28) and functional disability questionnaire (Health Assessment Questionnaire – HAQ), were obtained by direct interviews. The Female Sexual Function Index (FSFI) was used questionnaire which contains 19 items that assess six domains: sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction and pain. Results: 68 patients studied, of whom 54 (79.4%) reported sexual activity in the last four weeks. The participants were 49.7 ± 13.7 (mean ± SD) years old and the majority were married (61.4%). The mean DAS 28 was 3.6 ± 1.5 and the mean HAQ was 0.7. The prevalence of sexual dysfunction (FSFI ≤26) was 79.6%. There was no association of disease activity or of functional disability with the occurrence of sexual dysfunction in the female patients evaluated. Conclusion: The prevalence of sexual dysfunction found in this study was higher than that reported in the literature in healthy women. A knowledge of the extent of the problem is needed to provide adequate therapeutic options for these patients. .