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BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. METHODS: This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. RESULTS: Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. CONCLUSION: Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.
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Ameloblastoma , Ácidos Nucleicos Livres , Humanos , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Prospectivos , Mutação , Ácidos Nucleicos Livres/genéticaRESUMO
The circulating micronutrient pattern in type 2 diabetes mellitus (T2DM) may impact glycemic control and insulin resistance; however, there is a scarcity of studies that have evaluated the circulating micronutrient pattern in the T2DM population. Therefore, our objective was to identify circulating micronutrient pattern and their association with markers of glycemic control and insulin resistance in individuals with T2DM. We developed a cross-sectional observational study involving adults with T2DM in Sergipe, Brazil. We assessed plasma levels of magnesium, zinc, calcium, potassium, and serum 25-hydroxyvitamin D. Additionally, also measured fasting glucose levels, the percentage of glycated hemoglobin (%HbA1c), and calculated the homeostatic model assessment for insulin resistance (HOMA-IR). Patterns of body reserve were established using principal component analysis and categorized into quartiles. Binary logistic regression models were employed. We evaluated 114 individuals (63.7% women), with a median age and body mass index of 49 years and 29.6 kg/m², respectively. Two circulating micronutrient patterns were identified, explaining 62.5% of the variance: Pattern 1 (positive contributions from magnesium, zinc, calcium, and potassium) and Pattern 2 (positive contributions from 25-hydroxyvitamin D and zinc, with a negative contribution from potassium). Lowest quartile for Pattern 1 and Pattern 2 exhibiting a 4.32-fold (p = 0.019) and 3.97-fold (p = 0.038) higher likelihood of increasing HOMA-IR and %HbA1c values, respectively, compared to the larger quartiles. However, no associations were found between these patterns and fasting glucose values. Lowest quartile for both patterns of micronutrients was associated with inadequate metabolic control in individuals with T2DM.
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Diabetes Mellitus Tipo 2 , Controle Glicêmico , Resistência à Insulina , Oligoelementos , Adulto , Feminino , Humanos , Masculino , Glicemia/análise , Glicemia/metabolismo , Cálcio , Estudos Transversais , Glucose , Hemoglobinas Glicadas , Insulina , Magnésio , Micronutrientes , Potássio , ZincoRESUMO
Our objective was to evaluate the accuracy of predictive models for metritis spontaneous cure (SC) and cure among ceftiofur-treated cows using farm-collected data only, and with the addition of hemogram variables and circulating concentration of metabolites, minerals, and biomarkers (BM) of inflammation measured at time of diagnosis. Data related to parity, calving-related issues, BCS, rectal temperature, and DIM at metritis diagnosis were collected from a randomized clinical trial that included 422 metritic cows from 4 herds in Texas, California, and Florida. Metritis was defined as the presence of red-brownish, watery, and fetid vaginal discharge, and cure was defined as the absence of metritis 14 d after initial diagnosis. Cows were randomly allocated to receive systemic ceftiofur therapy (2 subcutaneous doses of 6.6 mg/kg of ceftiofur crystalline-free acid on the day of diagnosis and 3 d later; CEF) or to remain untreated (control). At enrollment (day of metritis diagnosis), blood samples were collected and submitted to complete blood count (CBC) and processed for the measurement of 13 minerals and BM of metabolism and inflammation. Univariable analysis to evaluate the association of farm-collected data and blood-assessed variables with metritis cure were performed, and variables with P ≤ 0.20 were offered to multivariable logistic regression models and retained if P ≤ 0.15. The areas under the curve for models predicting SC using farm data only and farm + BM were 0.70 and 0.76, respectively. Complete blood count variables were not retained in the models for SC. For models predicting cure among CEF cows, the area under the curve was 0.75, 0.77, 0.80, and 0.80 for models using farm data only, farm + CBC, farm + BM, and farm + CBC + BM, respectively. Predictive models of metritis cure had fair accuracy, with SC models being less accurate than models predictive of cure among CEF cows. Additionally, adding BM variables marginally improved the accuracy of models using farm collected data, and CBC data did not improve the accuracy of predictive models.
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Biomarcadores , Doenças dos Bovinos , Animais , Bovinos , Feminino , Biomarcadores/sangue , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/diagnóstico , Inflamação/veterinária , Inflamação/tratamento farmacológico , Endometrite/veterinária , Endometrite/tratamento farmacológico , Endometrite/diagnóstico , Antibacterianos/uso terapêuticoRESUMO
The main objective of this study was to evaluate the effect of ceftiofur on metritis cure, milk yield, reproductive performance, and culling up to 300 DIM. The secondary objective was to evaluate the effect of metritis cure at 5 (early cure [ECURE]) and 14 (late cure [LCURE]) days after diagnosis on milk production, reproduction, and culling. A total of 422 Holstein cows diagnosed with metritis from 4 herds located in Texas, California, and Florida were enrolled in a randomized clinical trial. Cows diagnosed with metritis (fetid, watery, reddish or brownish uterine discharge) were blocked by herd and parity and were randomly allocated to receive systemic administration of ceftiofur (CEF) or to remain untreated (CON). In addition, 399 nonmetritic cows (NMET) were included for comparison purposes. Metritis cure was evaluated at 5 and 14 d after diagnosis and was defined as the absence of metritis clinical signs. Logistic regression models were fitted to the data to assess the effect of treatment on metritis cure. Milk yield was analyzed using a mixed linear model, while logistic regression, Cox proportional hazard, and Kaplan-Meier survival analysis models were fitted to culling and reproduction data. Cows treated with CEF had 1.86 (95% CI: 1.22-2.81) and 1.68 (95% CI: 1.02-2.75) greater odds of being cured than CON cows at 5 and 14 d after diagnosis, respectively. No effect of CEF was observed for milk yield; however, NMET cows had greater milk yield compared with metritic cows (CEF = 36.0, 95% CI = 33.8-38.1; CON = 36.1, 95% CI = 33.9-38.2; NMET = 36.9 kg/d, 95% CI = 34.8-39.4). Likewise, no effect of CEF was observed on reproductive performance and culling. Nonetheless, the likelihood of conceiving for NMET cows was 1.72 (95% CI = 1.41-2.12) and 1.64 (95% CI = 1.33-2.00) times greater than for CEF and CON cows, respectively. Ceftiofur-treated and CON cows had 2.93 (95% CI = 1.90-4.51) and 2.37 (95% CI = 1.51-3.71) greater hazard of culling compared with NMET, respectively. Regardless of treatment, no differences between ECURE and LCURE were observed on milk yield, reproduction, and culling throughout the entire lactation, but cows that cured at 5 or 14 d after diagnosis had greater milk production in the first 60 DIM compared with cows that did not cure (NCURE). Cows in ECURE and LCURE also had a 1.59 (95% CI = 1.16-2.16) and 1.49 (95% CI = 1.08-2.05) greater hazard of pregnancy and 0.43 (95% CI = 0.26-0.71) and 0.56 (95% CI = 0.34-0.92) hazard of culling compared with NCURE. Ceftiofur therapy increased metritis cure, but benefits to productivity and longevity were not observed. Also, cows that fail to cure have impaired lactation performance, but no differences regarding timing of cure were observed.
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Antibacterianos , Doenças dos Bovinos , Cefalosporinas , Lactação , Leite , Animais , Bovinos , Feminino , Lactação/efeitos dos fármacos , Cefalosporinas/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Antibacterianos/uso terapêutico , Endometrite/veterinária , Endometrite/tratamento farmacológico , Reprodução/efeitos dos fármacosRESUMO
The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever.
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Doenças dos Bovinos , Febre , Lactação , Leite , Período Pós-Parto , Reprodução , Descarga Vaginal , Animais , Bovinos , Feminino , Descarga Vaginal/veterinária , Estudos Retrospectivos , Febre/veterinária , Gravidez , Estudos de CoortesRESUMO
Geopropolis resins are produced by stingless bees (Meliponinae), developed from the collection of resinous materials, waxes and exudates, from the flora of the region where stingless bees are present, in addition to the addition of clay or earth in its composition. Several biological activities are attributed to Ethanol Extracts of Geopropolis (EEGP). The bioactive properties are associated with the complex chemical composition that the samples have. This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections, mainly those caused by resistant strains of Staphylococcus aureus. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus, both at concentrations of 550â µg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65 % at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05±1.55â µg/mL. In the cytotoxicity test against HaCat cells, after 24â hours, EEGP induced cell viability at the three tested concentrations (550â µg/mL: 81.68±3.79 %; 1100â µg/mL: 67.10±3.76 %; 2200â µg/mL: 67.40±1.86 %). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S.â aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions.
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Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Animais , Abelhas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Própole/química , Própole/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: In the last decade, tissue-engineering strategies for regenerating the temporomandibular joint (TMJ) have been investigated. This may be a promising strategy for the minimally invasive restoration of joint integrity. OBJECTIVES: To evaluate whether dental pulp stem cells (DPSCs) loaded in a light-occured hydrogel made of gelatin methacryloyl (GelMA) enhance the regeneration of osteochondral defects in the rabbit TMJ. MATERIALS AND METHODS: Defects were filled with GelMA alone (control group; n = 4) or filled with GelMA loaded with rabbit DPSCs (experimental group; n = 4), In one group, the TMJ capsule was opened without creating a defect (sham group; n = 2). The following micro-CT parameters were analysed: bone volume to total volume ratio (BV/TV%) and bone mineral density (BMD). Histological evaluation was performed to assess cartilage regeneration features. A semi-quantitative scoring system was also used to evaluate the defects. RESULTS: All groups had no statistical difference regarding the micro-CT parameters. The highest mean healing score was found for the experimental group. After 4 weeks, there were no signs of hydrogel in either group or no signs of inflammation in the adjacent tissues. The tissue formed in the defect was dense fibrous connective tissue. CONCLUSION: Adding DPSCs to GelMA did not provide a regenerative enhancement in TMJ osteochondral defects. This resulted in similar micro-CT parameters after 4 weeks of healing, with improved signs of subchondral bone regeneration but no cartilage regeneration.
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Polpa Dentária , Hidrogéis , Animais , Coelhos , Articulação Temporomandibular , Engenharia Tecidual/métodos , Células-TroncoRESUMO
PURPOSE: The biceps brachii muscle (BBM) is a large and thick muscle on the ventral portion of the upper arm. The scientific literature reports the existence of extra heads. OBJECTIVE: The present work investigated the frequency of occurrence of BBM accessory head(s) in four different Anatomy Laboratories at universities in Northeast Brazil. MATERIAL AND METHODS: Once the upper limbs with an anatomical variation of the BBM heads were identified, the accessory head was evaluated for morphometric characterization (the length, width, and thickness). RESULTS: The sample consisted of 249 upper limbs and the outcomes were 26 members with BBM accessory heads (10.44% of the total sample). Among the 26 members studied was found a single accessory head in 22 (84.62%), two accessory heads in 3 (11.54%), and three accessory heads in 1 (3.85%). BBMs with one, two, and three accessory heads were found, with different origins. The average length, width, and thickness of these accessory heads were 169.39mm, 10.25mm, and 3.39mm, respectively. CONCLUSION: The frequency of BBM accessory heads in a population of northeastern Brazil in this cadaveric study was 10.44%.
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OBJECTIVE: The objective of this systematic review with meta-analysis was to critically evaluate the available data on the association of the BRAF V600E mutation and recurrence rate of ameloblastomas. MATERIALS AND METHODS: This systematic review was registered in Prospero (CRD42020183645) and performed based on the PRISMA statement. A comprehensive search in PubMed, Web of Science, Scopus and Cochrane Library databases was performed in order to answer the question "Does BRAF V600E mutation affect recurrence rate of ameloblastomas?" Methodological quality and risk of bias of the selected studies were assessed with JBI Critical Appraise Tool. Meta-analysis of quantitative data was conducted with RevMan 5.3 and Jamovi 2.3. RESULTS: The initial search identified 302 articles, and 21 met the inclusion criteria. A total of 855 subjects with ameloblastoma were included in the analysis. The pooled measures for frequency of BRAF V600E mutation was 65.30% (95% CI: 0.56-0.75; p < .001; I2 = 90.85%; τ = 0.205; p < .001), and the pooled recurrence rate was 25.30% (95% CI: 0.19-0.31; p < .001; I2 = 79.44%; τ = 0.118; p < .001). No differences in recurrence rate were observed between the BRAF V600E and wild type BRAF ameloblastomas, with a pooled Odds Ratio of 0.93 (95% CI: 0.56-1.54; p = .78; I2 = 31%; p = .09). CONCLUSIONS: BRAF V600E mutation is a frequent event in ameloblastomas, but does not increase nor reduce its recurrence rate, and thus have a limited value in predicting its prognosis.
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Ameloblastoma , Humanos , Ameloblastoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Mutação , PrognósticoRESUMO
The general assumption that the survival patterns of tropical and southern temperate birds are similar lacks empirical data from higher latitudes. Regional comparisons of New World species are rare, and this assumption has been based on data from African studies. Here, we estimate the survival rates of 88 tropical and southern temperate bird populations (69 species) from eight localities in South America to evaluate the hypothesis that the survival of these populations is homogeneous at the regional scale. We estimated survival based on the Cormack-Jolly-Seber model and compared values from different environments. The survival estimates ranged from 0.30 to 0.80 (0.56 ± 0.12). Apparent survival did not differ significantly between low-latitude tropical environments (03°S) and the other sites from high-latitudes (between 22° and 34°S). Despite a predicted positive trend, body size was not significantly related to survival among passerines. On the other hand, phylogenetic relationships explained more than a third of the variation in bird survival. Based on the largest available database on South American bird species, our findings support the hypothesis that bird survival is homogeneous, at the regional scale, along the southern hemisphere. In particular, we reinforce the hypothesis that climatic variation has a limited influence on bird survival in the southern hemisphere.
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Clima Tropical , Filogenia , América do Sul , Tamanho CorporalRESUMO
Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/complicações , Creatinina , Vitamina D , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteinúria/tratamento farmacológico , Suplementos NutricionaisRESUMO
Over the years, aircraft and spacecraft designs incorporated highly integrated and/or complex systems that can manage complex scenarios during its operation. In addition to the inherent complexity and/or high level of integration of those systems, the development process applied to aerospace programs is also challenged by other factors: program schedule, budget, multidisciplinary teams, new industry emerging technologies, large number of different processes and procedures that guide the activities along the development life cycle, and others. Given the fact many tasks executed during the development of such systems require human interaction, that yields the introduction of design errors that can contribute to the occurrence of non-desired system behaviors during operation phase. It is already recognized by the civil aviation industry that it is unfeasible to have a deterministic test set to demonstrate that such systems are completely free of such design errors. In that context, a huge effort is applied by the industry, by using qualitative methods to mitigate the occurrence of design errors during the development phases. This paper discusses how MBSE methodology applied together with a design assurance process could prevent such design errors, and presents an analysis showing how some events in aerospace industry where a design error was one of the contributing factors could be avoided.
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Aviação , Humanos , Aeronaves , EngenhariaRESUMO
The aim of this work was to evaluate the anti-inflammatory and antioxidant effects of ethyl acetate extract obtained from the leaves of Brazilian peppertree Schinus terebinthifolius Raddi (EAELSt). Total phenols and flavonoids, chemical constituents, in vitro antioxidant activity (DPPH and lipoperoxidation assays), and cytotoxicity in L929 fibroblasts were determined. In vivo anti-inflammatory and antioxidant properties were evaluated using TPA-induced ear inflammation model in mice. Phenol and flavonoid contents were 19.2 ± 0.4 and 93.8 ± 5.2 of gallic acid or quercetin equivalents/g, respectively. LC-MS analysis identified 43 compounds, of which myricetin-O-pentoside and quercetin-O-rhamnoside were major peaks of chromatogram. Incubation with EAELSt decreased the amount of DPPH radical (EC50 of 54.5 ± 2.4 µg/mL) and lipoperoxidation at 200-500 µg/mL. The incubation with EAELSt did not change fibroblast viability up to 100 µg/mL. Topical treatment with EAELSt significantly reduced edema and myeloperoxidase activity at 0.3, 1, and 3 mg/ear when compared to the vehicle-treated group. In addition, EAELSt decreased IL-6 and TNF-α levels and increased IL-10 levels. Besides, it modulated markers of oxidative stress (reduced total hydroperoxides and increased sulfhydryl contents and ferrium reduction potential) and increased the activity of catalase and superoxide dismutase, without altering GPx activity.
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Anacardiaceae , Antioxidantes , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Schinus , Quercetina , Brasil , Anacardiaceae/química , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Folhas de Planta/químicaRESUMO
The diffusion of photogenerated holes is studied in a high-mobility mesoscopic GaAs channel where electrons exhibit hydrodynamic properties. It is shown that the injection of holes into such an electron system leads to the formation of a hydrodynamic three-component mixture consisting of electrons and photogenerated heavy and light holes. The obtained results are analyzed within the framework of ambipolar diffusion, which reveals characteristics of a viscous flow. Both hole types exhibit similar hydrodynamic characteristics. In such a way the diffusion lengths, ambipolar diffusion coefficient, and the effective viscosity of the electron-hole system are determined.
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Extracellular adenosine plays important roles in modulating the immune responses. We have previously demonstrated that infection of dendritic cells (DC) by Leishmania amazonensis leads to increased expression of CD39 and CD73 and to the selective activation of the low affinity A2B receptors (A2B R), which contributes to DC inhibition, without involvement of the high affinity A2A R. To understand this apparent paradox, we now characterized the alterations of both adenosine receptors in infected cells. With this aim, bone marrow-derived DC from C57BL/6J mice were infected with metacyclic promastigotes of L. amazonensis. Fluorescence microscopy revealed that L. amazonensis infection stimulates the recruitment of A2B R, but not of A2A R, to the surface of infected DC, without altering the amount of mRNA or the total A2B R density, an effect dependent on lipophosphoglycan (LPG). Log-phase promastigotes or axenic amastigotes of L. amazonensis do not stimulate A2B R recruitment. A2B R clusters are localized in caveolin-rich lipid rafts and the disruption of these membrane domains impairs A2B R recruitment and activation. More importantly, our results show that A2B R co-localize with CD39 and CD73 forming a "purinergic cluster" that allows for the production of extracellular adenosine in close proximity with these receptors. We conclude that A2B R activation by locally produced adenosine constitutes an elegant and powerful evasion mechanism used by L. amazonensis to down-modulate the DC activation.
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5'-Nucleotidase/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Caveolina 1/metabolismo , Células Dendríticas/imunologia , Leishmaniose/imunologia , Microdomínios da Membrana/imunologia , Receptor A2B de Adenosina/metabolismo , Animais , Células Dendríticas/metabolismo , Células Dendríticas/parasitologia , Células Dendríticas/patologia , Imunidade , Imunomodulação , Leishmania/imunologia , Leishmaniose/metabolismo , Leishmaniose/parasitologia , Leishmaniose/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Macrófagos/patologia , Masculino , Microdomínios da Membrana/parasitologia , Microdomínios da Membrana/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Obesity is a major public health problem, and there is increasing scientific interest in its mechanisms, as well as a search for new compounds with antioxidant and anti-inflammatory properties that can minimize the metabolic complications associated with its pathology. One potential source of these compounds is natural products; Among these, flavonoids are a promising group of natural substances. Flavonoids are active constituents with diverse biological activities and are widely found in plants kingdom. Numerous studies have shown that flavonoids can effectively inhibit obesity and related metabolic disorders. The review synthesizes recent evidence in respect of progress in the understanding of the anti-obesity effects of flavonoids. Such effects which occurs through the modulation of proteins, genes and transcriptional factors involved in decreasing lipogenesis, increasing lipolysis, expenditure energy, stimulating fatty acids B-oxidation, digestion and metabolism of carbohydrates. In addition to mitigating inflammatory responses and suppress oxidative stress. A better understanding of the modulating effects and mechanisms of flavonoids in relation to obesity will allow us to better use these compounds to treat or even prevent obesity and its associated comorbidities.
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Fármacos Antiobesidade , Flavonoides , Obesidade , Fármacos Antiobesidade/farmacologia , Produtos Biológicos/farmacologia , Flavonoides/farmacologia , Humanos , Obesidade/prevenção & controleRESUMO
The genus Ctenomys has been widely used in karyotype evolution studies due to the variation in their diploid numbers. Ctenomys minutus is characterized by intraspecific variation in diploid number (2n = 42, 46, 48, and 50), which makes it an interesting model to investigate genomic rearrangements mechanisms that could lead to different cytotypes in this species. Thereupon, it has been already shown that DNA methylation may participate in chromosome structure. Therefore, we aimed to investigate whether telomeres and global DNA methylation had a role in the genome rearrangements that led to this variation in C. minutus. We also realized an analysis for the presence of intrachromosomal telomeric repeats (ITRs) by fluorescence in situ hybridization. Our study demonstrated that neither telomere length nor DNA methylation had significant differences among the cytotypes. However, if only females were considered, there were significant differences for telomere length and methylation. Young individuals, regardless of their cytotypes, had the most methylated DNA. Regarding the ITRs, we found a signal on chromosome 1 in 2n = 50b. No evidence was found that telomere length or methylation could have influenced chromosomal rearrangements, although new cytotypes seem to have emerged within the distribution of parental cytotypes by the accumulation of different chromosomal rearrangements.
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Roedores , Telômero , Humanos , Animais , Hibridização in Situ Fluorescente , Metilação , Cariótipo , Cariotipagem , Roedores/genética , Telômero/genéticaRESUMO
The present study investigates dumbbell-shaped nematic liquid crystal shells. Using molecular dynamics (MD) simulations, we consider the effects of an external electric field on nematic ordering by computing the average molecular alignment's time evolution and equilibrium configuration. We show that the number and location of topological defects are strongly affected by the external field, with the orientational ordering's equilibrium configuration depending on field direction about the shell's long axis. For a transverse external field, it is verified that the defect rearrangement presents a non-linear dynamics, with a field independent characteristic time scale delimiting the short and long time regimes. Effects associated with varying the shell's Gaussian curvature are also analyzed.
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OBJECTIVE: The objective of this systematic review with meta-analysis was to critically evaluate the available data on sensitivity and specificity of IHC compared with molecular tests in the detection of BRAF V600E mutation in ameloblastomas. MATERIALS AND METHODS: This systematic review was performed based on the PRISMA statement and registered in Prospero (CRD42021259117). PubMed, Web of Science, Scopus, and Cochrane Library databases were searched for observational studies to answer the question "What is the diagnostic accuracy of immunohistochemistry compared with molecular tests for the diagnosis of BRAF V600E mutation in ameloblastomas?". Methodological quality and risk of bias assessment of the selected studies were based on the QUADAS-2. Meta-analysis based on hierarchical SROC curve model and summary measures for sensitivity and specificity were computed. RESULTS: A total of 226 records were found, but only 05 articles met the inclusion criteria, with 277 FFPE specimens of ameloblastoma included in the quantitative analysis. The sensitivity of the IHC compared to molecular tests ranged from 0.71 to 1.00, while all of the included studies showed perfect specificity (1.00). Pooled measures for sensitivity and specificity were 0.95 [95% CI 0.89, 1.00] and 1.00 [95% CI 0.95, 1.00], respectively. The diagnostic odds ratio was 4.05, and the AUC for SROC curve was calculated as 0.979. CONCLUSIONS: BRAF V600E-specific IHC using VE1 antibody showed extremely high sensitivity and specificity when compared with molecular tests in the detection of the mutation in ameloblastomas.
Assuntos
Ameloblastoma , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Biomarcadores Tumorais/genética , Humanos , Imuno-Histoquímica , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Sensibilidade e EspecificidadeRESUMO
The present report describes the implementation of an emergency operations center to coordinate the response to the COVID-19 pandemic in the municipality of Rio de Janeiro, Brazil. Following the public health emergency management framework proposed by the World Health Organization (WHO), this temporary center (COE COVID-19 RIO) started operating in January 2021. The report is organized along five themes: legal framework; structure, planning, and procedures; institutional articulation; health information for decision-making; and risk communication. Major advances obtained with the initiative include improvements in governance for the management of COVID-19, increase in the synergy among sectors and institutions, improved information sharing in relation to COVID-19 prevention and control measures, innovation in epidemiologic analyses, and gains in transparency and decision-making opportunities. In conclusion, even if conceived at an advanced stage of the pandemic in the municipality of Rio de Janeiro, the COE COVID-19 RIO has played a relevant role in shaping the city's responses to the pandemic. Also, despite its temporary character, the experience will leave a lasting legacy for the management of future public health emergencies in the municipality of Rio de Janeiro.
En el presente artículo se describe la experiencia al establecerse un centro de operaciones de emergencia (COE) para coordinar la respuesta a la pandemia de COVID-19 en el municipio de Rio de Janeiro (Brasil). Siguiendo el modelo de gestión de emergencias de salud pública promovido por la Organización Mundial de la Salud (OMS), este centro temporal se activó en enero del 2021. El informe se estructuró con base en cinco ejes temáticos: marco legal; estructura, planes y procedimientos; articulaciones institucionales; información en materia de salud para sustentar las decisiones; y comunicación sobre riesgos. Entre los principales avances relacionados con esta iniciativa cabe destacar los adelantos en cuanto a la gobernanza para organizar la forma de enfrentar la COVID-19, el aumento de la sinergia entre los sectores y las instituciones correspondientes, un mayor intercambio de información sobre las medidas de prevención y control de la enfermedad, innovación en los análisis epidemiológicos, mayor transparencia en la toma de decisiones y decisiones tomadas de manera más oportuna. Se llegó a la conclusión de que este COE, a pesar de que había sido establecido en una fase avanzada de la pandemia en la ciudad, tuvo un papel importante en la estructuración de la respuesta. Sin embargo, a pesar de su carácter temporal, la experiencia demostró ser un importante legado para enfrentar futuras emergencias de salud pública en el municipio de Rio de Janeiro.