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OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.
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Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte−PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte−PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.
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Anticorpos Monoclonais Humanizados , Artrite Reumatoide , Plaquetas , Monócitos , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Plaquetas/citologia , Citometria de Fluxo , Humanos , Interleucina-6/antagonistas & inibidores , Monócitos/citologiaRESUMO
The objective of this study was to evaluate changes in the bacterial community in sugarcane silage, in distinct soil types along the storage period. We depicted the bacterial community associated with sugarcane, before and after ensiling, through a massive sequencing of the gene 16S rRNA using MiSeq platform. The ensilage process shifted the composition of the bacterial community from the heterofermentative lactic acid bacteria Leuconostoc to bacteria belonging to the genera Acinetobacter, Ralstonia and Novosphingobium. However, this shift did not convey statically significant differences in alfa diversity metrics. In addition, similarity percentage analysis showed that the bacterial Operational Taxonomic Units that were primarily responsible for the observed differences were Leuconostoc, Pseudomonas, Acinetobacter, Ralstonia, Fructobacillus, Novosphingobium, Lactobacillus, Burkholderia and Clostridium sensu stricto 1. The storage period was the most important factor responsible for changes in the bacterial community of silages. Results confirmed that the type of soil did not influence the dissimilarity found among samples.
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Saccharum , Silagem , Bactérias/genética , Fermentação , RNA Ribossômico 16S/genética , Silagem/análise , Silagem/microbiologiaRESUMO
INTRODUCTION: To reach the diagnosis of giant cell arteritis (GCA), signs, symptoms, laboratory tests, imaging findings, and occasionally anatomopathological results from temporal artery biopsy are evaluated. This study describes the results of an algorithm analysis based on clinical and ultrasound evaluation of patients with suspected GCA, highlighting its diagnostic utility by contrasting its use in different clinical suspicion scenarios. METHOD: Prospective multicenter study evaluating patients referred with suspected GCA through a preferential circuit (fast track), grouping them according to low or high clinical suspicion of GCA. Each of these scenarios is evaluated by biopsy and ultrasound for all patients, resulting in positive, indeterminate, or negative outcomes, yielding six possible groups. Potential areas of improvement are explored, emphasizing that, following a negative or indeterminate ultrasound, 18-FDG-PET-CT could be recommended. We analyze the results and application of a diagnostic algorithm, confirming its efficiency and applicability based on whether there is high or low clinical suspicion. RESULTS: Sixty-nine patients (41 in the high suspicion group and 28 in the low suspicion group). There were 41 new diagnoses of GCA: 35 in the high suspicion group and 6 in the low suspicion group. Using ultrasound alone, the initial algorithm has an overall diagnostic efficiency of 72.5%, which improves to 80.5% when including 18F-FDG-PET/CT. The negative predictive value of ultrasound in patients with low clinical suspicion is 84.6%, and the positive predictive value of ultrasound in patients with high suspicion is 100%, improving sensitivity from 57.1% to 80.8% with 18F-FDG-PET/CT in this scenario. Temporal artery biopsy was performed on all patients, with no differences in sensitivity or specificity compared to ultrasound. In cases where all three tests - ultrasound, biopsy, and 18F-FDG-PET/CT - are performed, sensitivity increases to 92.3% in patients with high clinical suspicion. CONCLUSION: In situations of high clinical suspicion, the algorithm provides sufficient information for the diagnosis of GCA if ultrasound is positive. A negative ultrasound is sufficient to rule out the diagnosis in the context of low clinical suspicion. 18-FDG-PET-CT may be useful in patients with high suspicion and negative or indeterminate ultrasound results.
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Algoritmos , Arterite de Células Gigantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ultrassonografia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Estudos Prospectivos , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , Biópsia , Pessoa de Meia-Idade , Fluordesoxiglucose F18 , Artérias Temporais/patologia , Artérias Temporais/diagnóstico por imagem , Sensibilidade e Especificidade , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: To investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB). METHODS: A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months. RESULTS: Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA. CONCLUSION: Our study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.
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Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia , Estudos Retrospectivos , BiópsiaRESUMO
BACKGROUND: To examine the performance of the new 2022 American College of Rheumatology (ACR)/EULAR classification criteria for giant cell arteritis (GCA) in routine clinical care, compared with the 1990 ACR GCA classification criteria. METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR criteria was tested in our real-life cohort of GCA patients with proven vasculitis by temporal artery biopsy or imaging (a necessary pre-requisite to apply the new criteria is the presence of a confirmed diagnosis of medium- or large-vessel vasculitis). The performance of classification criteria was evaluated in all patients with GCA across different subsets of the disease. Patients with GCA were compared with unselected controls with suspected GCA. RESULTS: A total of 136 patients with proven GCA were identified. The new criteria had a sensitivity of 92.6% and a specificity of 85.2%. According to the clinical phenotypes, the sensitivity was 98.8% in cranial GCA, 92% in extracranial large vessel (LV) GCA and 75% in occult systemic GCA. These data are much better than those observed with the 1990 ACR classification criteria, which showed a sensitivity of 66.1% and a specificity of 85.1% for the total sample, with a sensitivity of 89.1% in cranial GCA, 24% in extracranial LV-GCA and 35.7% in occult systemic GCA. Ten (7.4%) patients in our cohort did not fulfil either of the criteria sets (8 with occult systemic GCA and 2 with extracranial LV-GCA). The sensitivity of the new criteria in patients with occult systemic and extracranial LV-GCA could be greatly improved assigning more weight (3 points) to some imaging findings (axillary involvement and FDG-PET activity throughout the aorta). CONCLUSION: Our study confirms that the new classification criteria are more sensitive in real-life settings than the old ACR criteria across all clinical phenotypes.
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Arterite de Células Gigantes , Reumatologia , Humanos , Estados Unidos , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/patologia , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
Aloe vera (Aloe barbadensis Miller) gel is a frequently used ingredient in many food pro-ducts, particularly beverages, due to its reported health benefits. Studies have identified acemannan, a polysaccharide rich in mannose units which are partially or fully acetylated, as the primary bioactive compound in Aloe vera gel. The acemannan content and its degree of acetylation (DA) were measured in 15 different commercial beverages containing Aloe vera at varying concentrations (from 30% to 99.8%) as listed on the label. Other biopolymers such as pectins, hemicelluloses, and cellulose were also evaluated. Flavoured beverages (seven samples labelled as containing from 30% to 77% Aloe vera) presented low levels of acemannan (<30 mg/100 g of fresh sample) and were fully deacetylated in most cases. These samples had high levels of other polymers such as pectins, hemicelluloses, and cellulose, likely due to the addition of fruit juices for flavour. Unflavoured beverages (eight samples, with Aloe vera concentrations above 99% according to their labels) had variable levels of acemannan, with only three containing more than 160 mg/100 g of fresh sample. In fact, four samples had less than 35 mg acemannan/100 g of fresh sample. DA levels in all but one sample were lower than 35%, possibly due to processing techniques such as pasteurization causing degradation and deacetylation of the acemannan polymer. Legislation regarding Aloe vera products is limited, and manufacturers are not required to disclose the presence or quality of bioactive compounds in their products, leaving consumers uncertain about the true properties of the products they purchase.
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OBJECTIVE: The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA). METHODS: We systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method. RESULTS: The literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence. In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64-0.84), angiographic stabilization was observed in 86% (0.77-0.94) and relapses in 12% (0.05-0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28-21.16). Adverse events were observed in 8% of patients (0.02-0.16). Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy. In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17-0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29-32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 - 0.80). Relapses were observed in 21% of cases (0.14- 0.28) and adverse events in 28% (0.12-0.46). Comparison of LEF with MTX showed similar efficacy and tolerance. CONCLUSION: LEF is well tolerated and might be effective for patients with TAK and GCA.
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Antirreumáticos , Arterite de Células Gigantes , Arterite de Takayasu , Humanos , Leflunomida/uso terapêutico , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Takayasu/tratamento farmacológico , Glucocorticoides/uso terapêutico , Estudos de Coortes , RecidivaRESUMO
Introduction: Uniform chromosome abnormalities are commonly seen in early pregnancy loss, with analyses of the product of conception suggesting the presence of mosaic autosomal trisomy in â¼10% of cases. Although chromosomal mosaicism occurs in a minority of embryos, their relative commonality and uncertainty regarding associated transfer outcomes have created discussion at both the clinical and research levels, highlighting the need to understand the clinical conditions associated with the incidence of embryo mosaicism. Methods: We took advantage of a preimplantation genetic testing for aneuploidy (PGT-A) database created from 2019 to 2022 in more than 160 in vitro fertilization (IVF) clinics in Brazil, the second-largest world market for IVF. We carried out descriptive statistical and associative analyses to assess the proportions of mosaicism associated with clinical conditions and reported incidence by chromosome, clinic origin, and biopsy operator. Results: Chromosomal analysis revealed that most mosaic aneuploidies occurred in the last three chromosomes, with 78.06% of cases having only one chromosome affected. Low mosaicism in trisomy represented the most ordinary form, followed by low mosaicism in monosomy. We identified associations between low (negatively-associated) and high mosaicism (positively-associated) and maternal age, indication (male factor and uterus/ovarian factor negatively associated with low and high mosaic, respectively), day of blastocyst development (day five has an overall better outcome), morphology grade (lower quality increased the chances of low and high mosaicism), origin (vitrified oocyte and embryo increased the rates of low and high mosaicism, respectively), and embryo sex (male embryos negatively associated with low mosaic). Discussion: With these results, we hope to foster an improved understanding of the chromosomal mosaicism linked with distinct clinical conditions and their associations in Brazil.
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In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39-CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39-CD73- cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.
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Artrite Reumatoide , Linfócitos T CD8-Positivos , Humanos , 5'-Nucleotidase/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Apirase/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Inflamação , Interleucina-6RESUMO
OBJECTIVE: The main study objective was to determine how giant cell arteritis (GCA) is diagnosed in our clinical practice and whether the EULAR recommendations have influenced the diagnostic procedures used. METHODS: ARTEritis of the Rheumatology Spanish Society -Sociedad Española de Reumatología (ARTESER) is a multicentre observational retrospective study conducted in 26 hospitals with support from the Spanish Society of Rheumatology. All patients diagnosed with GCA between 1 June 2013 and 29 March 2019 were included. The gold standard for the diagnosis of GCA was the judgement of the physician in charge, according to clinical criteria, supported by data available from laboratory tests, imaging studies (ultrasound, positron emission tomography (PET) and MRI/CT angiography) and temporal artery biopsy (TAB) when available. RESULTS: We included 1675 patients with GCA (mean age±SD (76.9±8.1) years, 1178 women (70.3%)). Of these, 776 patients had a positive TAB (46.3%), 503 (30.0%) positive ultrasound, 245 positive PET (14.6%) and 64 positive MRI/CT angiography (3.8%). These percentages changed substantially over the study. From 2013 to 2019, the use of ultrasound in diagnosis grew from 25.8% to 52.9% and PET from 12.3% to 19.6%, while use of TAB decreased from 50.3% to 33.3%. CONCLUSIONS: Biopsy was the most widely used diagnostic test for confirming GCA, but use of imaging as a diagnostic tool has grown in recent years. Following publication of the 2018 EULAR recommendations, ultrasound has displaced biopsy as the first-line diagnostic test; TAB was performed in a third and PET in a fifth of cases.
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Arterite de Células Gigantes , Feminino , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia , UltrassonografiaRESUMO
This study evaluated the rehydration approach of mature corn grains as an alternative for high-moisture corn grain silage production in distinct corn hybrids, storage period, cultivation locations and kernel maturity at plant harvest. High-moisture corn was used as a control. The dry matter content and pH of the silage were measured, and the bacterial community associated with corn grains pre- and post-ensiling was also assessed through 16S rRNA high-throughput sequencing. The decrease in pH value was directly linked to an ecological microbial succession of Enterobacteriales and Actinomycetales to Lactobacillales in the silage at 120 days after storage, either in rehydrated or high-moisture corn. These results were similar for both maize production locations and hybrids tested. Finally, the similarity between the ensiling processes including rehydrated corn and the high-moisture corn grain silages proves the reliability of the rehydration approach as an alternative for the maintenance of a successful bacterial community structure and composition capable of producing high-quality silages from dent and flint corn hybrids in tropical conditions.
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Hidratação , Alimentos em Conserva/microbiologia , Microbiota/fisiologia , Silagem/microbiologia , Zea mays/microbiologiaRESUMO
This study evaluated changes in the bacterial community in high-moisture and rehydrated corn grain silage, and their correlation with fermentation quality attributes in distinct corn hybrids, the storage period, and kernel maturity at plant harvest. Most silages achieved good fermentation (pH<4.2). Rehydrated corn had a higher pH across all storage periods evaluated and increased dry matter losses. Leuconostoc and Lactococcus were the dominant genera in fresh material, while Lactobacillus and Acetobacter were prevalent in silages. Clostridium and Enterococcus prevailed in rehydrated corn after 120 days storage, and Clostridium was highly and positively correlated with acetone, butyric acid, and 2,3-butanediol contents. The storage period and kernel maturity were the most important factors responsible for changes in the bacterial community of silages. Results confirmed the existence of a specific bacterial microbiome that was unique for each maturity and storage time. Variations in these factors also affected the fermentation quality through influencing the bacterial community.
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Bactérias/crescimento & desenvolvimento , Microbiota , Silagem/microbiologia , Zea mays/microbiologia , Acetobacter/crescimento & desenvolvimento , Acetobacter/metabolismo , Bactérias/metabolismo , Clostridium/crescimento & desenvolvimento , Clostridium/metabolismo , Enterococcus/crescimento & desenvolvimento , Enterococcus/metabolismo , Fermentação , Hibridização Genética , Lactobacillales/crescimento & desenvolvimento , Lactobacillales/metabolismo , Silagem/análise , Água , Zea mays/genética , Zea mays/crescimento & desenvolvimentoRESUMO
We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet's disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ± SD BCVA (0.8 ± 0.3 LogMAR vs. 0.6 ± 0.3 LogMAR; p = 0.03), mean ± SD RNFL (190.5 ± 175.4 µm vs. 183.4 ± 139.5 µm; p = 0.02), mean ± SD MT (270.7 ± 23.2 µm vs. 369.6 ± 137.4 µm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10-61.5) mg/day at baseline to. 2.5 (0-5) mg/day after one year of follow-up; p = 0.001. After a mean ± SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.
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Myo4p is a nonessential type V myosin required for the bud tip localization of ASH1 and IST2 mRNA. These mRNAs associate with Myo4p via the She2p and She3p proteins. She3p is an adaptor protein that links Myo4p to its cargo. She2p binds to ASH1 and IST2 mRNA, while She3p binds to both She2p and Myo4p. Here we show that Myo4p and She3p, but not She2p, are required for the inheritance of cortical ER in the budding yeast Saccharomyces cerevisiae. Consistent with this observation, we find that cortical ER inheritance is independent of mRNA transport. Cortical ER is a dynamic network that forms cytoplasmic tubular connections to the nuclear envelope. ER tubules failed to grow when actin polymerization was blocked with the drug latrunculin A (Lat-A). Additionally, a reduction in the number of cytoplasmic ER tubules was observed in Lat-A-treated and myo4Delta cells. Our results suggest that Myo4p and She3p facilitate the growth and orientation of ER tubules.
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Retículo Endoplasmático/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Divisão Celular/fisiologia , Corrente Citoplasmática/fisiologia , Retículo Endoplasmático/ultraestrutura , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestrutura , Mutação/genética , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/genética , Tiazóis/farmacologia , TiazolidinasRESUMO
Sickle cell anemia is an inherited systemic hemoglobinopathy that affects hemoglobin production in red blood cells, leading to early morbidity and mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the ß-globin gene (HBB) that changes a glutamic acid to a valine in the protein. We present a case report of a fertile couple, both carriers of the sickle cell anemia mutation, with one affected daughter. Six cycles of assisted reproductive techniques were performed, resulting in 53 embryos in cleavage stage. Each embryo was biopsied and analyzed for pre-implantation genetic diagnosis (PGD) by fluorescent polymerase chain reaction, using polymorphic markers of the region of interest followed by capillary electrophoresis in an automated genetic analyzer. HLA Compatible and normal embryos for the mutation represented 3 (5.66%); while the carriers and compatible 6 (11.32%); therefore, embryos matching those of the affected daughter represented 9 (16.98%). A selected embryo in blastocyst stage was transferred, resulting in a healthy male newborn, who had the umbilical cord blood cells collected and stored. The affected daughter was immunosuppressed and received transplanted cells from the umbilical cord blood of her brother; the treatment was successful. Embryo selection using PGD technologies represent the most effective treatment plan for parents who want to have a healthy child, and it could cure another child already affected by inherited hemoglobinopathy.
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Anemia Falciforme/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Teste de Histocompatibilidade/métodos , Diagnóstico Pré-Implantação/métodos , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/genética , Blastocisto/metabolismo , Blastocisto/patologia , Criança , Transferência Embrionária , Feminino , Ligação Genética , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Linhagem , Gravidez , Técnicas de Reprodução Assistida , Relações entre IrmãosRESUMO
The aim of this study was to assess the diagnostic value of the Psoriatic Arthritis Screening Evaluation (PASE) and Early Psoriatic Arthritis Screening Questionnaire (EARP) questionnaires in the ultrasonographic detection of enthesitis, synovitis, and tenosynovitis. A cross-sectional study was done in a total of 96 consecutive patients. Double blind clinical examination and echographic assessment were performed. A receiver-operating characteristic (ROC) model analysis for the questionnaires was established using echographic findings as reference variable. The optimal diagnostic point was determined following a Youden analysis model from the obtained data, calculating sensitivity and specificity along with predictive values, likelihood ratio, and diagnostic odds ratio. A logistic regression analysis was used to determine possible predictor variables of enthesitis, synovitis, and tenosynovitis. When enthesitis, synovitis, and tenosynovitis were considered as one outcome for the diagnostic study of the PASE or EARP questionnaire, there were no statistically significant differences among the score of the study groups and the rest of patients. The PASE and EARP tests had a diagnostic performance for enthesitis, synovitis, and tenosynovitis that followed the expected pattern when the prevalence of findings is low. In these cases, the tests increase their negative predictive value, being particularly interesting in ruling out the disease.
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Artrite Psoriásica/diagnóstico , Psoríase/complicações , Inquéritos e Questionários , Sinovite/diagnóstico , Tenossinovite/diagnóstico , Adulto , Idoso , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Psoríase/diagnóstico por imagem , Sensibilidade e Especificidade , Sinovite/complicações , Sinovite/diagnóstico por imagem , Tenossinovite/complicações , Tenossinovite/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVE: To investigate the frequency and type of giant cell arteritis (GCA)-related ischemic complications in a series of patients with GCA who, for a substantial period of time (i.e., at least 3 mo), lacked vascular symptoms and presented with apparently isolated polymyalgia rheumatica (PMR). METHODS: Retrospective follow-up study of an unselected population of 167 patients with GCA diagnosed from 1985 to 2014. RESULTS: In all, 18 patients (11%) developed GCA on a background of a prior history of PMR. They were diagnosed as having isolated PMR because they did not have clinical evidence of GCA at diagnosis and exhibited a prompt and complete response to low-dose steroid therapy. However, during the course of treatment, 17 patients later experienced an arteritic relapse with the development of typical craniofacial symptoms, and one patient developed signs of upper extremity vascular insufficiency, resulting in the diagnosis of large-vessel GCA. The median time to GCA diagnosis from the initiation of low-dose steroid therapy was 9 ± 14.4 mo (range: 3-39). At the time of GCA diagnosis, severe ischemic complications were observed in 50% (9/18) of the patients. Of these patients 22% (4/18) were considered to have "true" occlusive disease (i.e., permanent visual loss, stroke, and/or limb claudication). Late inflammation of the aorta and its branches occurred in 4 (22%) of the patients during long-term follow-up. CONCLUSION: Patients with GCA presenting with apparently isolated PMR have a significant risk of developing transient or permanent disease-related ischemic complications; these complications occurred in 50% of the cases.