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Background: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. Results: In two patients, the diagnosis of 46,XX SRY + DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. Conclusions: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD.

Objectives Autologous haematopoietic stem cell transplantation (AHSCT) is a disease-modifying treatment for patients with severe SSc. Here, we aimed at assessing cardiopulmonary function outcomes of SSc patients after AHSCT. Methods Twenty-seven SSc adult patients treated with AHSCT were included in this retrospective study. Most had the diffuse cutaneous subset (93%) and pulmonary involvement (85%). Before and 12 months after AHSCT, patients underwent cardiopulmonary exercise testing, transthoracic echocardiography, pulmonary function test with diffusing capacity for carbon monoxide (DLCO), 6-min walk test (6MWT) and quality of life evaluations. Results After AHSCT, the peak VO2 increased from 954 to 1029 ml/min (P = 0.02), the percentage of predicted peak VO2 increased from 48.9 to 53.5 m (P = 0.01), and the distance measured by the 6MWT increased from 445 to 502 m (P = 0.01), compared with baseline. Improvements in peak VO2 correlated positively with improvements in 6MWT distance, and negatively with a decrease in resting heart rate. At baseline, patients with DLCO >70% had higher peak VO2 values than those with DLCO Conclusion AHSCT improves the aerobic capacity of SSc patients probably reflecting combined increments in lungs, skeletal muscle and cardiac function.

The aim of this study was to evaluate the concordance of the diagnoses made by senior rheumatologists and those made by residents in rheumatology and by general practitioners (GPs).In this cohort, 497 patients referred by GPs from August 1, 2018 to December 16, 2019 were evaluated first by a second-year resident in rheumatology. After clinical rounds, the diagnoses by senior rheumatologists were assumed as the criterion standard and defined the prevalence of the rheumatic diseases, divided into 5 groups: rheumatoid arthritis, spondyloarthritis, other connective tissue diseases and vasculitis, nonautoimmune rheumatic diseases, and nonrheumatic diseases. The follow-up ended on November 30, 2020. We calculated sensibility, specificity, positive predictive value, negative predictive value, and κ coefficient of the diagnosis by GPs and residents.The diagnoses were changed for 58% of the referral letters. Diseases of low complexity, such as fibromyalgia and osteoarthritis, accounted for 50% of the diagnoses. Compared with senior rheumatologists, residents in rheumatology had κ0.6 for all the groups, whereas GPs had κ0.5, with the worst performance for nonautoimmune rheumatic disease (κ = -0.18) and nonrheumatic disease (κ = 0.15). In terms of level of complexity, 46% of the letters were inappropriate.We found a poor level of diagnostic agreement between GPs and the rheumatology team. General practitioners had difficulties diagnosing and treating rheumatic diseases, referring patients that should be treated in the primary level of health care. One year of training in rheumatology made residents' skills comparable to those of senior rheumatologists.

Introdução: doenças crônicas como asma brônquica, alergias respiratórias ou doenças agudas recorrentes, como gripes,frequentemente acometem as crianças. Tais condições exigem o uso de medicamentos, normalmente sob a forma de xaropes, que podem se apresentar como genéricos ou de referência. A alta concentração em sacarose e o baixo pH dessas formulações, assim como o uso noturno e a falta de higienização após sua administração, são alguns fatores que podem contribuir para o potencial cariogênico e erosivo desses medicamentos. Objetivo: o objetivo deste estudo foi avaliar in vitro o potencial cariogênico e erosivo de xaropes infantis, de referência e genéricos, a partir de suas propriedades físico-químicas e identificar seus principais componentes a partir da análise de bulas e rótulos. Metodologia: foram analisados oito medicamentos de referência e os oito genéricos equivalentes, os quais foram avaliados quanto ao pH, a acidez titulável, a presença de sólidos solúveis totais (ºBrix) e a composição em sacarose econservantes através da análise de bulas e rótulos. Resultados: constatou-se que 75% da amostra apresentou pH abaixo do crítico para desmineralização do esmalte dentário. A presença da sacarose e do ácido cítrico foi observada em 43,75% dos medicamentos, especialmente entre aqueles com altos valores de titulação. Conclusão: a maioria dos medicamentos apresentou pH abaixo do pH crítico para dissolução do esmalte dentário, havendo uma ampla variação da acidez titulável. As bulas dos medicamentos não informavam quanto ao risco de erosão dentária e de cárie, apesar da presença de sacarose em algumas formulações

Resumo As feiras de Ciências são ferramentas muito relevantes no processo de ensino-aprendizagem para o aluno, pois possibilitam a compreensão de conceitos estudados, em sala de aula, por meio de demonstrações experimentais. Desse modo, o presente trabalho teve como objetivo demonstrar experimentos químicos envolvendo a contextualização e a interdisciplinaridade da feira de Ciências na Escola Estadual Plínio Ramos Coelho. Para atender ao objetivo do trabalho foi realizada a feira de ciências no evento intitulado “III Mostra do Saber”, quatro bolsistas do PIBID ficaram responsáveis por confeccionar e executar seus experimentos demonstrativos, sendo todos na área da Química, com intuito de contribuir no processo ensino -aprendizagem dos alunos e sociedade presente no evento, além de envolver a contextualização da cientificidade com o cotidiano também abrange a interação comunidade/escola e professor/aluno. Os resultados obtidos foram satisfatórios, pois os bolsistas do PIBID, alunos da escola e comunidade, em geral, trocaram experiências por meio dos experimentos realizados na Feira de Ciências, proporcionando assim mais conhecimento para todos os participantes. Por fim, conclui-se que por meio do projeto realizado é possível relacionar e compreender conteúdos vistos anteriormente, em sala de aula, por meio de demonstrações químicas, reforçando interações entre comunidade e escola e aproximando mais professor e aluno.Palavras-chave: Experimentos Científicos. PIBID. Química. Abstract Science fairs are relevant tools in the student's teaching-learning process, as they enable the understanding of concepts studied in the classroom through experimental demonstrations. Thus, this project aimed to demonstrate chemical experiments involving the contextualization and interdisciplinarity of the science fair at the Plínio Ramos Coelho State School. To meet the project objective, the science fair was held at the event entitled “III Mostra do Saber”, four PIBID scholarship holders were responsible for making and executing their demonstration experiments, all of them in the chemistry area, in order to contribute to the teaching-learning process of students and society present at the event, in addition to involving the scientificity contextualization with everyday life, it also encompasses the interaction with community / school and teacher / student. The results obtained were satisfactory, since the PIBID scholarship holders, students from the school and the community in general exchanged experiences through the experiments carried out at the science fair, thus providing more knowledge for all the participants. Finally, it is concluded that through the project carried out it is possible to relate and understand content previously seen in the classroom through chemical demonstrations, reinforcing interactions between community and school and bringing the teacher and student closer. Keywords: Scientific Experiments. PIBID. Chemistry.

Stem cell transplantation has been investigated as treatment for severe and progressive systemic sclerosis (SSc) for the past 25 years. To date, more than 1000 SSc patients have been transplanted worldwide. Overall and event-free survival have increased over the years, reflecting stricter patient selection criteria and better clinical management strategies. This review addresses long-term outcomes of transplanted SSc patients, considering phase I/II and randomized clinical trials, as well as observational studies and those assessing specific aspects of the disease. Clinical outcomes are discussed comparatively between studies, highlighting advances, drawbacks and controversies in the field. Areas for future development are also discussed.

Brain injury in sickle cell disease (SCD) comprises a wide spectrum of neurological damage. Neurocognitive deficits have been described even without established neurological lesions. DTI is a rapid, noninvasive, and non-contrast method that enables detection of normal-appearing white matter lesions not detected by conventional magnetic resonance imaging (MRI). The aim of the study was to evaluate if stem cell transplantation can revert white matter lesions in patients with SCD. Twenty-eight SCD patients were evaluated with MRI and DTI before and after allogeneic hematopoietic stem cell transplantation (HSCT), compared with 26 healthy controls (HC). DTI metrics included fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity maps, global efficiency, path length, and clustering coefficients. Compared to HC, SCD patients had a lower FA (p = 0.0086) before HSCT. After HSCT, FA increased and was not different from healthy controls (p = 0.1769). Mean MD, RD, and AD decreased after HSCT (p = 0.0049; p = 0.0029; p = 0.0408, respectively). We confirm previous data of white matter lesions in SCD and present evidence that HSCT promotes recovery of brain injury with potential improvement of brain structural connectivity.

Background: Molecular biology and cytogenomics methods have gained space in the clinical investigation for patients with disorders/differences in sexual development (DSD). Here we aimed to evaluate the role of SNP-array in achieving a molecular diagnosis in a sample of 22 Brazilian patients with syndromic DSD of unknown etiology, and to compare the relationship between the clinical diagnosis and the SNP-array results.Methods: 22 patients with DSD associated with syndromic features in several systems other than the genital tract were included in the study and underwent search for genomic copy number variations (CNVs) by SNP-array.Results: In two patients, the diagnosis of 46,XX SRY+ DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene were associated with genital atypia and syndromic characteristics in two patients with 46, XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataract, a 12Kb deletion on chromosome 10 was found, justifying the congenital cataract.Conclusions: The SNP-array technique identified the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD. In one patient the array contributed to partially clarify the patient's syndromic phenotype, but not the genital atypia.

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

BackgroundIn the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center.Patients and methodsThis is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan’s skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function.ResultsMedian (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud’s disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura.ConclusionsAutologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

The main objective of this article is to understand the role of urban toponymy as hegemonic discourses of the social role of women in the formation of the city of Londrina, Paraná. Hence, we make use of biographical texts attached to the bills that name public places. In the impossibility of presenting all the questions engendered by this writing, we opted for a specific analysis on the representations of gender contained in the biographies of women chosen for such honors. We propose a reflection on the imbrications between biographical writing, History and gender relations, observing the city of Londrina, which is also marked by a strong memorialistic discourse on the pioneering spirit of those – especially men – who built the city. In the period studied, more than four thousand places were created, with the names of women being in 781 of them. Thus, we observe that the toponymy with names of women is underrepresented, and highly marked by delimited social roles. El objetivo principal de este artículo es comprender el papel de la toponimia urbana como discursos hegemónicos del papel social de la mujer en la formación de la ciudad de Londrina-PR. De esta manera, hacemos uso de textos biográficos adjuntos a los proyectos de ley que nombran lugares públicos. Ante la imposibilidad de presentar todas las cuestiones que engendra este escrito, optamos por un análisis específico sobre las representaciones de género contenidas en las biografías de mujeres elegidas para tales nombramientos. Proponemos una reflexión sobre las imbricaciones entre escritura biográfica, Historia y relaciones de género, observando la ciudad de Londrina, que también está marcada por un fuerte discurso memorialista sobre el espíritu pionero de quienes – especialmente los hombres – construyeron la ciudad. En el período estudiado se crearon más de cuatro mil lugares públicos, de los cuales a 781 se les pusieron nombres de mujeres. Así, observamos que la toponimia con nombres de mujeres está subrepresentada, y claramente marcada por roles sociales delimitados. O presente artigo tem como objetivo compreender o papel da toponímia urbana enquanto discursos hegemônicos do papel social da mulher na formação da cidade de Londrina, Paraná. Valemo-nos de textos biográficos anexados aos projetos de leis que nomeiam logradouros públicos. Na impossibilidade de apresentarmos todas as questões engendradas por essa escrita, optamos por uma análise específica sobre as representações de gênero contidas nas biografias de mulheres escolhidas para tais nomeações. Propomos uma reflexão sobre as imbricações entre a escrita biográfica, a História e as relações de gênero, observando a cidade de Londrina, que é também marcada por forte discurso memorialístico sobre o pioneirismo, daqueles que construíram a cidade, especialmente homens. No período estudado foram criados mais de quatro mil logradouros, sendo que os nomes de mulheres estão em 781. Assim, observamos que a toponímia com tais está sub-representada, e acentuadamente marcada por papeis sociais delimitados.

Autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a promising treatment option in severely affected and refractory patients with autoimmune diseases. This is a retrospective survey of patients reported to the EBMT registry between 1998 and 2019, who received AHSCT for TAK. Data from six patients treated with AHSCT for refractory TAK have been identified, five were female (83%), median age 25 (9-39) years. All patients were pretreated with a median of 6 (4-8) lines of therapy, including steroids (six patients), methotrexate (five patients), cyclophosphamide, mycophenolate mofetil or infliximab (four patients), tocilizumab or etanercept (two patients). Conditioning included cyclophosphamide and rabbit anti-thymocyte globulin in all patients. At 6 months post transplantation, remission was obtained in all cases, which persisted at 12 months in five cases. Four patients reactivated TAK at a median time of 27 (7-52) months after AHSCT, and three resumed disease-modifying therapy. At last follow-up, all patients were alive, two patients were in remission (off-therapy), two patients improved compared with baseline, and two patients were in complete and partial remission, respectively, under immunosuppressive treatment. This retrospective case-series demonstrates that AHSCT has the potential to provide significant clinical responses in TAK patients, but large prospective trials are necessary to confirm these preliminary data.

Context Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD). Objective To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients. Design/patients 209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS. Results Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively. Conclusions The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.

Objective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples. Results: On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT. Conclusion: Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury.

BACKGROUND/OBJECTIVE We sought to evaluate if autologous hematopoietic stem cell transplantation (AHSCT) influences the functional status of systemic sclerosis (SSc) patients. METHODS From 2014 to 2018, a cohort of 27 SSc patients was assessed before, and at 6 and 12 months after AHSCT for modified Rodnan's skin score (mRSS), mouth opening, hand grip strength, range of motion (ROM), functional ability of upper limbs (DASH questionnaire and Cochin hand function scale-CHFS), 6-minute walk test (6MWT), and quality of life (SF-36 questionnaire). Linear regression models with random effects and Spearman's test were used for statistical analysis. RESULTS At 6 and 12 months after AHSCT, respectively, we observed significant improvement of mRSS (p < 0.01 and p < 0.01), mouth opening (p = 0.02 and p < 0.01), hand function (DASH, p < 0.01 and p < 0.01; CHFS, p < 0.01 and p < 0.01; strength, p < 0.01 and p < 0.01), physical capacity (6MWT, p = 0.02 and p = 0.03) and physical (p < 0.01 and p < 0.01) and mental (ns and p = 0.02) component scores of SF-36. At 12 months after AHSCT, ROM measurements improved (p < 0.05) in five out of six evaluated joints in both hands, compared to baseline. Correlation was significant between physical capacity and quality of life (R = 0.62; p < 0.01), between DASH and quality of life (R = -0.48; p = 0.03), and between skin involvement and wrist ROM measures (dominant hand, R = -0.65, p < 0.01; non-dominant hand, R = -0.59; p < 0.01). CONCLUSIONS AHSCT enhances the functional status of SSc patients in the first year of follow-up, significantly improving hand function, physical capacity and quality of life. These results are interpreted as positive outcomes of AHSCT for SSc.

Objectives The rationale of autologous haematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells and the infused autologous haematopoietic stem cells promote reconstitution of a naïve and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in SSc patients treated with AHSCT. Methods Peripheral blood was harvested from 22 SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signalling pathways and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry. Results Naïve B cell frequencies increased from 60 to 360 days post-AHSCT compared with pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19+CD24hiCD38hi and CD19+CD24hiCD27+ frequencies increased at 180 days. Moreover, the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase increased in B cells reconstituted post-AHSCT. Notably, CD19+CD24hiCD38hi Bregs recovered their ability to suppress production of Th1 cytokines by CD4+ T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-β1-producing B cells decreased following AHSCT. Conclusion Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to re-establishment of self-tolerance and clinical remission.

Autoimmune diseases are an important field for the development of bone marrow transplantation, or hematopoietic stem cell transplantation. In Europe alone, almost 3000 procedures have been registered so far. The Brazilian Society for Bone Marrow Transplantation (Sociedade Brasileira de Transplantes de Medula Óssea) organized consensus meetings for the Autoimmune Diseases Group, to review the available literature on hematopoietic stem cell transplantation for autoimmune diseases, aiming to gather data that support the procedure for these patients. Three autoimmune diseases for which there are evidence-based indications for hematopoietic stem cell transplantation are multiple sclerosis, systemic sclerosis and Crohn's disease. The professional stem cell transplant societies in America, Europe and Brazil (Sociedade Brasileira de Transplantes de Medula Óssea) currently consider hematopoietic stem cell transplantation as a therapeutic modality for these three autoimmune diseases. This article reviews the evidence available.

Background The reproducibility and reliability of the modified Rodnan’s Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other’s scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen’s Kappa Coefficient, Intraclass Correlation Coefficient, Kendall’s Coefficient and Spearman’s test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen’s Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.

BACKGROUND/OBJECTIVE Interstitial lung disease stands among the leading causes of death in systemic sclerosis (SSc) patients. Autologous hematopoietic stem cell transplantation (AHSCT) has been proven superior to conventional immunosuppressive therapy in severe and progressive SSc. Here, pulmonary quantitative measurements were obtained in high-resolution computed tomography (HRCT) scans of patients with SSc before and after AHSCT. METHODS The medical records of thirthy-three patients who underwent AHSCT between 2011 and 2017 were evaluated for clinical and tomographic features at baseline (pre-AHCST) and 18 months after the procedure. Quantitative analysis of HRCT images by a fully automated program calculated lung volumes, densities, attenuation percentiles, and vascular volume. Patients were divided into 2 groups, according to changes in forced vital capacity (FVC). The "best response" group included patients that had an increased FVC of 10% or greater, and the "stable response" group included those who had a decreased or an increased FVC of less than 10%. RESULTS In the best response group (15 patients), there was reduction (p < 0.05) of mean lung density and density percentile values after AHSCT. In the stable response group (18 patients), there were no significant changes in lung volumes and pulmonary densities after AHSCT. Pulmonary HRCT densities showed moderate/strong correlation with function. CONCLUSIONS Quantitative HRCT analysis identified significant reduction in pulmonary densities in patients with improved pulmonary function after AHSCT. Lung density, as evaluated by the quantitative HRCT analysis tool, has potential to become a biomarker in the evaluation of interstitial lung disease treatment in patients with SSc.

To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements. At the 1-year post-AHSCT evaluation of the total set of transplanted SSc patients, thymic rebound led to renewal of the immune system, with higher T-cell receptor (TCR) diversity, positive correlation between recent thymic emigrant and Treg counts, and higher expression of CTLA-4 and GITR on Tregs, when compared with pretransplant levels. In parallel, increased bone marrow output of newly generated naive B-cells, starting at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At 6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10 levels than before transplant. When the nonresponder patients were evaluated separately, Treg and Breg counts did not increase after AHSCT, and high TCR repertoire overlap between pre- and posttransplant periods indicated maintenance of underlying disease mechanisms. These data suggest that clinical improvement of SSc patients is related to increased counts of newly generated Tregs and Bregs after AHSCT as a result of coordinated thymic and bone marrow rebound.

Clay minerals are layered materials with a number of peculiar properties, which find many relevant applications in various industries. Since they are easily found everywhere, they are particularly attractive due to their economic viability. In the cosmetic industry, clay minerals are often used as excipients to stabilize emulsions or suspensions and to modify the rheological behavior of these systems. They also play an important role as adsorbents or absorbents, not only in cosmetics but also in other industries, such as pharmaceuticals. This reviewer believes that since this manuscript is presented as covering topical applications that include pharmaceuticals, some types of clay minerals should be considered as a potential material to be used as drug delivery systems. We review several applications of clay minerals to dermocosmetic products, relating them to the underlying properties of these materials and exemplifying with a number of clay minerals available in the market. We also discuss the use of clay minerals in topically-applied products for therapeutic purposes, specially for skin treatment and protection. Fil: Moraes, Jemima Daniela Dias. Federal University of São Paulo, Graduate Program in Translational Medicine, Medicine Department; Brasil Fil: Bertolino, Silvana Raquel Alina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Cuffini, Silvia Lucia. Federal University of São Paulo, Graduate Program in Material Science Engineering; Brasil Fil: Ducart, Diego Fernando. University of Campinas - Unicamp, Institute of de Geosciences; Brasil Fil: Bretzke, Pedro Eriberto. University of Vale do Itajaí, Graduate Program in Pharmaceutical Science, Nucleus of Chemical-Pharmaceutical Investigations; Brasil Fil: Leonardi, Gislaine Ricci. University of Campinas, Faculty of Pharmaceutical Science; Brasil. Federal University of São Paulo, Graduate Program in Translational Medicine, Medicine Department; Brasil

Background Autologous hematopoietic stem cell transplantation (AHSCT) is nowadays a clinical reality as an effective and safe approach to treat systemic sclerosis patients’ refractory to conventional therapy using immune suppressive drugs, although its immune mechanisms are still not completely understood1,2,3. Objectives To evaluate the reconstitution of B-cell subsets in SSc patients following AHSCT. Methods Peripheral blood samples were harvested from twenty-four SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. The immunophenotyping, regulatory B-cell IL-10 production and suppressive assays were assessed by flow cytometry. Results Compared to baseline, naive B-cells (CD19+CD27-IgD-) significantly decreased in frequency and absolute counts at 30 days post-AHSCT, followed by an increase at 360 days. There was a transient decrease of non-class-switched memory-B-cell (CD19+CD27+IgD+) frequency at 30 days, followed by an increase at 360 days. In addition, mature class-switched memory-B-cells (CD19+CD27+IgD-) and plasma cell (CD19+CD27highIgD-) decreased (P Conclusion Following transplantation, SSc patients displayed increased naive-B-cells values and decreased memory B-cells, which might contribute to self-tolerance reestablishment, disease remission and clinical improvement on these patients. SSc patients showed increases of Breg numbers after AHSCT as well as an increase of IL-10 production, suggesting improvements in immunoregulatory mechanisms. References [1] Burt, et al. Lancet2013:381(9872):1116–24. [2] van Laar, et al. JAMA2014;311(24):2490–8. [3] Sullivan, et al. N Engl J Med2018;378:35–47. Acknowledgement Funding was provided by the Sao Paulo Research Foundation (FAPESP) and Coordination for the Improvement of Higher Education Personnel (CAPES). Disclosure of Interests None declared

The main complain of patients with partial androgen insensitivity patients (PAIS) is undervirilization signs and the small penile length. Supplemental androgen therapy has enhanced virilization in only a few patients with PAIS. Aromatase inhibitors as anastrozole and letrozole are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450 reducing estrogen and estrone levels and increasing LH and FSH levels and consequently testosterone levels. We hypothesized that the combination of high-dose testosterone with anastrozole can maintain a sustained elevated testosterone levels and also deviated testosterone metabolization from estrogen to DHT, therefore increasing penile length. Case Report This experimental treatment was proposed and both patient and parents willing to participate. Patient was firstly evaluated at 7 yrs of age. The hemizygous c.2599G>C; p.V867L AR in the ligand-binding domain (LBD) was found in both affected siblings. He was previously submitted to three unsuccessful genital masculinizing surgeries and bilateral orchidopexia. The external genitalia presented a microphalus (penile length of 2 cm, -4.5 SDS), perineal hypospadias and bilateral topic testis. He received testosterone cypionate (50 mg IM injections monthly, for 3 times at age of 7 and 200 mg IM injections monthly, for 4 times at age of 8); topic DHT gel (5-10 g/daily for three months at age of 7 yrs). At age of 12.3 yrs, the genital masculinization surgeries were completed, penile length was 3.5 cm (-2.6 SDS), testicular size of 2.6x1.5 cm and pubic hair Tanner II stage. LH and FSH levels were (9.4 and 3.2 IU/L respectively), testosterone (304 ng/dL), DHT (26 ng/dL) and estradiol (

Abstract: The sexuality of 46,XY DSD individuals can be affected by several factors as external genitalia appearance, negative body image, traumas, social stigma, and previous genital surgery. Previous studies has been reported an impaired sexual quality of life (SexQoL) in 46,XY DSD individuals in comparison with controls. To observe aspects regarding sexual life, 144 individuals with 46,XY DSD (100 female; 44 male) were enrolled in this study. All of them were adults (>16 years old) and had completed all surgical treatments. Sexual life and fertility issues were assessed using self-developed questionnaire with likert-scale questions. Sexual orientation was assessed on the basis of orientation, sexual behavior and sexual attraction. For comparison, the cohort was divided into 3 subgroups (A: gender at adulthood; B: genitalia appearance at birth; and C: male individuals at adulthood who were assigned as male versus who changed from female to male). About fertility issues, 12 individuals (8%) had children (7 male; 5 female). 10 out of 12 were adopted children and 2 patients had children by Intravaginal insemination (IVI). Desire of fertility was similar in women and men (78.3%, 80.7% respectively; p = NS). Fear of rejection due to infertility was reported by 28% (34 out of 117). More women than men considered infertility a barrier to a steady relationship (p=0.04). Regarding sexual orientation, more than 90% referred themselves as heterosexual. Homosexuality was reported by 4% in both genders. Most 46,XY DSD women reported androphilic sexual attraction and female sexual behavior (have sex with male partners), regardless of the appearance of external genitalia. The opposite (gynephilic sexual attraction and male sexual behavior) was observed in most male patients either in individuals who were assigned male at birth and in individuals who changed from female to male. Regarding sexual life, there was significant difference between males and females on sexual fantasies, masturbation practice and fixed sexual partner, which were more frequent in males. Nevertheless, both gender reported a similar sexual life satisfaction (76% and 80%). All sexual parameters were similar comparing individuals who changed from female to male and who were assigned as male. In conclusion, sexual life satisfaction was reported by the majority of adult patients with 46,XY DSD in both gender. Among female patients, the appearance of external genitalia did not influence on sexuality, once the surgical correction of atypical genitalia have been performed. In male individuals, the sexual life was similar either if they were assigned as male or changed for that gender later. Fertility desire was common among 46,XY DSD people, regardless of gender or 46,XY etiology, which should be taken into consideration in the 46,XY DSD management.

Submitted by Daniela de Moraes Bessa (dani_bessa_@hotmail.com) on 2019-07-25T15:22:23Z No. of bitstreams: 1 Disserta????oDanielaBessa_PPGCASA2019.pdf: 3712380 bytes, checksum: d5ccb2511e95dc3c9da668e03adde4d9 (MD5) Rejected by PPGCASA Programa de Ci??ncias do Ambiente e Sustentabilidade na Amaz??nia (ppgcasasecretaria@ufam.edu.br), reason: est?? faltando a Ata de Defesa e a Carta de Encaminhamento para Autodep??sito. on 2019-07-25T19:31:11Z (GMT) Submitted by Daniela de Moraes Bessa (dani_bessa_@hotmail.com) on 2019-07-31T17:58:46Z No. of bitstreams: 3 Disserta????oDanielaBessa_PPGCASA2019.pdf: 3711992 bytes, checksum: b0593da81a4ac5092a7fbd833c541d07 (MD5) Daniela_Deposito_Disserta????o(1).pdf: 604165 bytes, checksum: b6de8d7946473aa3f74626faff7d507e (MD5) Ata_DanielaBessa.jpg: 456916 bytes, checksum: 6b33ded1245bebf02d79693b1f52aa9d (MD5) Approved for entry into archive by PPGCASA Programa de Ci??ncias do Ambiente e Sustentabilidade na Amaz??nia (ppgcasasecretaria@ufam.edu.br) on 2019-08-07T19:24:45Z (GMT) No. of bitstreams: 3 Disserta????oDanielaBessa_PPGCASA2019.pdf: 3711992 bytes, checksum: b0593da81a4ac5092a7fbd833c541d07 (MD5) Daniela_Deposito_Disserta????o(1).pdf: 604165 bytes, checksum: b6de8d7946473aa3f74626faff7d507e (MD5) Ata_DanielaBessa.jpg: 456916 bytes, checksum: 6b33ded1245bebf02d79693b1f52aa9d (MD5) Approved for entry into archive by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br) on 2019-08-09T18:05:12Z (GMT) No. of bitstreams: 3 Disserta????oDanielaBessa_PPGCASA2019.pdf: 3711992 bytes, checksum: b0593da81a4ac5092a7fbd833c541d07 (MD5) Daniela_Deposito_Disserta????o(1).pdf: 604165 bytes, checksum: b6de8d7946473aa3f74626faff7d507e (MD5) Ata_DanielaBessa.jpg: 456916 bytes, checksum: 6b33ded1245bebf02d79693b1f52aa9d (MD5) Made available in DSpace on 2019-08-09T18:05:12Z (GMT). No. of bitstreams: 3 Disserta????oDanielaBessa_PPGCASA2019.pdf: 3711992 bytes, checksum: b0593da81a4ac5092a7fbd833c541d07 (MD5) Daniela_Deposito_Disserta????o(1).pdf: 604165 bytes, checksum: b6de8d7946473aa3f74626faff7d507e (MD5) Ata_DanielaBessa.jpg: 456916 bytes, checksum: 6b33ded1245bebf02d79693b1f52aa9d (MD5) Previous issue date: 2019-03-22 CAPES - Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior (92)991874309 Carbon is the fundamental chemical element for life on Earth. However, an imbalance in its biogeochemical cycle has contributed to a serious environmental problem that this planet is facing and that affects all beings indistinctly. Carbon-derived gases (CO2 and CH4), due to the property of retaining heat in the atmosphere, are considered as greenhouse gases (GHG) and these have promoted global climate change. The Amazon has a leading role in the planet's climate stabilization, because it has a carbon stock ranging from 50.8 to 57.5 billion tons, almost 7 times more than the annual global carbon emission. Considering that much of the anthropic actions are anchored in human behavior, it becomes vital to understand the ways of thinking of people who live in direct contact with this phenomenon in the Amazon forest and what practices these people are related to GHG emissions and with the conservation of the forest. By unveiling such understandings it is possible to propose effective and efficient educational programs for a sustainable relationship with the forest and this cycle and thus contribute to the mitigation of climate change. This study therefore sought to investigate the understanding of the processes that involve the biogeochemical cycle of carbon and its relations with the Amazon forest, between those who live and depend directly on the resources of that forest, that is, residents of communities of a Conservation Unit. In this study, we analyzed the environmental perceptions of the inhabitants of the Baixo Juru??-AM Extractive Reserve on the carbon cycle and its relationship with the forest. A participant observation, collective interview with 14 residents and 30 semi-structured interviews were carried out using the topographic-topological modeling technique. This consists of using a model that represents the geographical area and types of land use and forest resources, with which the interviewee responds in an interactive way to the questions raised about the topic. The results show that, despite having different understandings about what it is about, where it is found, how this element moves around the planet and on the relation of this with the forest the inhabitants recognize the existence of something that is not seen, but which interferes with organisms and the ecosystem. It is also noted that traditional and scientific knowledge reflects a reading both on the symbolic and on the physical world. In many cases, these knowledges complement each other, others confront each other. These results corroborate the need to unveil such perceptions, in order to propose educational processes that make possible the understanding of these concepts and to stimulate holistic GHG reduction practices. O carbono ?? o elemento qu??mico fundamental para a vida na Terra. Entretanto, um desequil??brio em seu ciclo biogeoqu??mico tem contribuindo com um grave problema ambiental que atinge a todos indistintamente na Terra. Os gases derivados de carbono (CO2 e CH4), devido a propriedade de reter calor na atmosfera, s??o considerados gases de efeito estufa (GEE) e esses t??m promovido a mudan??a clim??tica global. Pelo fato de possuir um estoque de carbono que varia entre 50,8 a 57,5 bilh??es de toneladas, quase 7 vezes mais do que a emiss??o global anual de carbono, a Amaz??nia tem um papel de destaque na estabiliza????o clim??tica do planeta. Considerando que muito das a????es antr??picas est??o ancoradas no comportamento humano, se torna vital compreender quais s??o os modos de pensar de pessoas que vivem em contato direto com esse fen??meno na floresta amaz??nica e quais as pr??ticas dessas pessoas est??o relacionadas com as emiss??es de GEEs e com a conserva????o da floresta. Ao desvelar tais entendimentos ?? poss??vel propor programas educativos eficazes e eficientes para que se tenha uma rela????o sustent??vel com a floresta e com esse ciclo, e consequentemente contribuir para a mitiga????o da mudan??a clim??tica. Esse estudo buscou, portanto investigar o entendimento dos processos que envolvem o ciclo biogeoqu??mico do carbono e das suas rela????es com a floresta amaz??nica, entre aqueles que vivem e dependem diretamente dos recursos dessa, ou seja, moradores de comunidades de uma Unidade de Conserva????o (UC). Neste, analisou-se as percep????es ambientais dos moradores da Reserva Extrativista do Baixo Juru??-AM sobre o ciclo do carbono e a sua rela????o com a floresta. Foi realizada observa????o participante, entrevista coletiva com 14 moradores e 30 entrevistas semiestruturadas com uso da t??cnica de modelagem topogr??fica- topol??gica, que consiste em utilizar uma maquete que representa a ??rea geogr??fica e tipos de uso de ocupa????o da terra e recursos florestais, com as quais o entrevistado responde, de modo interativo aos questionamentos feitos acerca do tema. Os resultados mostram que, apesar de terem entendimentos diversos sobre o que se trata, onde se encontra, como esse elemento se movimenta no planeta e sobre a rela????o desse com a floresta, os moradores reconhecem a exist??ncia de algo que n??o ?? visto, mas que interfere nos organismos e no ecossistema. Nota-se tamb??m, que o saber tradicional e o cient??fico reflete uma leitura, tanto sobre o mundo simb??lico, quanto sobre o mundo f??sico. Em muitos casos, esses saberes se complementam, em outros se confrontam. Tais resultados corroboram a necessidade de desvelar tais percep????es, afim de propor processos educativos que possibilitam a compreens??o desses conceitos e de estimular pr??ticas de redu????o dos GEEs derivados do carbono de forma hol??stica.

Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS).To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression.Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018.Patients were randomized to receive HSCT along with cyclophosphamide (200 mg/kg) and antithymocyte globulin (6 mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55).The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios.Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference, -1.7; 95% CI, -2.03 to -1.29; P .001). There were no deaths and no patients who received HSCT developed nonhematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events).In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety.ClinicalTrials.gov Identifier: NCT00273364.

Objective: To evaluate the association between insulin-dose adjusted A1C (IDAA1c) and microvascular complications (MC) and hypoglycemia in a representative Brazilian population of Type 1 diabetes mellitus (T1DM) patients.Research Design and Methods: This was a cross-sectional study based on a previous study, “Microvascular Complications in Type 1 Diabetes: a comparative analysis of patients treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) and conventional medical therapy (CT)”. The 168 patients in that study (144 from CT plus 24 from AHST) were re-subdivided into two groups, according to their IDAA1c values (30 patients had IDAA1c ≤ 9; 138 had IDAA1c > 9). Then, the prevalence of MC (diabetic renal disease, neuropathy, and retinopathy), hypoglycemia (blood glucose 9 group had at least one complication (p = 0.044). Regarding hypoglycemic events, the proportion of individuals who reported at least 1 episode of hypoglycemia in the last month was 43.3 and 64.7% from the IDAA1c ≤ 9 and IDAA1c > 9 groups, respectively (p = 0.030). Regarding severe hypoglycemia, the proportion of patients presenting at least one episode in the last month and the rate of episode/patient/month were similar between groups (6.7 vs. 13.2%; p = 0.535; and 0.1/patient/month vs. 0.25/patient/month; p = 0.321).Conclusion: In a representative Brazilian population of T1DM patients, those with IDAA1c ≤ 9 presented a lower frequency of MC, as well as fewer episodes of hypoglycemia, in the month prior to the analysis.

Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD.

As Unidades de Atenção Primária à Saúde (APS) devem ser a principal porta de entrada para o Sistema Único de Saúde (SUS). O objetivo deste estudo foi analisar acesso dos usuários do SUS às unidades de APS a partir de três dimensões: disponibilidade, acessibilidade e aceitabilidade. Trata-se de um estudo de caso com múltiplas abordagens realizado na Região de Saúde de Barretos, São Paulo. A investigação foi pautada em três aspectos que influenciam o acesso: fatores do sistema de saúde, percepção dos gestores e dos usuários. As fontes de evidências utilizadas foram dados secundários, análise espacial das unidades de APS com auxílio de Sistema de Informação Geográfica (GIS), entrevista com gestores da pesquisa Política, Planejamento e Gestão das Regiões e Redes de Atenção à Saúde no Brasil e entrevista com usuários do Programa Nacional de Melhoria de Acesso e da Qualidade da Atenção Básica. Os principais achados na dimensão da disponibilidade foram que o número da unidade de APS está de acordo com o recomendado pelo Ministério da Saúde. De acordo com os gestores nas unidades, há falta de integração entre os serviços e os médicos, que estão centrados nos principais centros urbanos da região. Para os usuários, o tempo de espera está dentro das expectativas. Na acessibilidade, a distribuição geográfica das unidades está adequada na maior parte dos municípios, onde os usuários realizam o trajeto em até 10 minutos e consideram como sendo fácil ou muito fácil o acesso, mas a maioria dos gestores desconhecem critérios de distribuição geográfica dos recursos. Na aceitabilidade, grande parte dos usuários aceita o cuidado recebido pelos profissionais de saúde das unidades de APS. O acesso às unidades de APS na região de Barretos revelou resultados positivos, porém a maior parte não possui ocupação profissional. Nos achados, fica evidenciada a necessidade dos gestores públicos aprimorarem a gestão em alguns aspectos como introdução de sistema de informação para agendamento de consultas, ampliação do horário de atendimento, utilização de SIG, pois permite a identificação de áreas mais vulneráveis e aquelas que necessitam de investimentos - e a melhoria na comunicação para que a população entenda o papel das unidades de APS para a prevenção e promoção à saúde, as quais possam se efetivar como coordenadoras do cuidado das Redes de Atenção à Saúde (RAS). A APS fortalecida permite que o sistema se organize nos três níveis da atenção, obtenha melhor desempenho no planejamento das ações, otimize os recursos e contribua para a melhoria das condições de vida da população na região The Units of Primary Health Care (PHC) must be the main gateway to the Unified Health System (SUS). This study aims to analyze the access from users to PHC through three dimensions: availability, accessibility and acceptability. This is a case study with multiple approaches which took place in the region of Barretos, São Paulo. The research was focused considering three aspects that can influence the access: health systems factors, the perception of health professionals and users. The sources of evidence used were secondary data, spatial analyses of the Primary Care Center (PCC) using the Geographic Information System (GIS), interviews with the managers from the research Regions and Health Care Network and with users of the National Program to Improve Access and Quality of Primary Care . The main findings in the dimension of availability were that the number of units of PCC is according to the recommendation from the Ministry of Health. According to the units managers, there is a lack of integration between the services and the phisicians that are located in the main urban areas. The waiting time for the users, for scheduling appointments, is according to their expectation. Concerning the accessibility, the geographic location of the units are adequate for users in most counties. Users take about ten minutes to arrive to the units. They consider the access to it to be easy or very easy, but managers dont know the geographical location criteria for the resources. Regarding acceptability most users accept the Health Care Services, in the PHC. The access to the units in Barretos region had positive results, therefore most of the users dont have a professional occupation. It was evident in the findings the need for public managers to improve some management aspects, like to implement a new information system for scheduling appointments, extension of operation hours to the users, the utilization of a GIS, which can identify the more vulnerable areas, the ones that needs financial investments and improvement in communication, so that the population understands the role of the PHC units to prevent, promote and protect health, which can be effective as coordinators for the care of the Health System Network. The robust PHC allows the organization of the system on three health care levels, achieving a better performance on planning its action, optimizing the resources and contributing to the a better well-being for the population on its region

Background Systemic sclerosis (SSc) is characterised by skin thickening and visceral involvement, leading to impairment of physical function, daily life activities and quality of life. Severe cases usually have poor prognosis, despite conventional immunosuppressive treatment. Autologous hematopoietic stem cell transplantation (AHSCT) has been investigated as treatment for patients with severe SSc and promotes reduction of skin thickening and at least stabilisation of visceral involvement. There are no reports in the literature addressing the influence of AHSCT on hand function and physical capacity of SSc patients. Objectives To evaluate the impact of AHSCT on skin involvement, hand function, physical capacity and quality of life (QoL) of SSc patients. Methods This is a prospective longitudinal study of a cohort of 27 SSc patients who underwent AHSCT at a University Hospital in the state of Sao Paulo, Brazil. Patients were evaluated before, and at 6, 12 and 24 months after transplant. The evaluations included modified Rodnan skin score (mRSS), hand function (hand-grip strength, finger-to-palm distance – FTP, range of motion measures, DASH and COCHIN questionnaires), mouth opening, six-minute walk test (6MWT) and quality of life questionnaire (SF-36). Results were subjected to statistical analyses and significance levels were established at p Results Twenty-seven patients were evaluated before and at 6 months after transplant, 22 of which were additionally evaluated at 12 months, and 13 patients at 24 months post-transplant. At 12 months after AHSCT, patients presented significant improvement of mRSS (p Conclusions AHSCT enhances the functional status of SSc patients, significantly improving skin involvement, hand function, physical capacity and quality of life. These results can be interpreted as positive outcomes of AHSCT for SSc. References [1] van Laar, et al. JAMA2014;311(24):2490–8. [2] Del Papa, et al. Bone Marrow Transplantation2017;52:53–58. [3] Burt, et al. Lancet2013:381(9872):1116–24. [4] Sullivan, et al. N Engl J Med2018;378:35–47. Disclosure of Interest None declared