Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 607
Filtrar
1.
Biomed Res Int ; 2020: 1061407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32016112

RESUMO

Asthma is a common respiratory disease with inflammation in the lungs. Exosomes and microRNAs (miRNAs) play crucial role in inflammation, whereas the role of exosomal miRNA in asthma remains unknown. Here, we aimed to identify the key exosomal miRNAs and their underlying mechanisms involved in scorpio and centipede (SC) treatment in asthma. Eighteen mice were randomly divided into three groups: control group, asthma group, and SC treatment group. Effect of SC was assessed by hematoxylin-eosin staining and real-time PCR. Exosomes from asthma and SC treatment groups were analyzed by small RNA-seq. Results revealed SC significantly alleviated the pathogenesis of asthma and suppressed the release of inflammatory cytokines. A total of 328 exosomal miRNAs were differentially expressed between the exosomes from asthma and SC-treated mice, including 118 up- and 210 downregulated in SC-treated mice. The altered exosomal miRNAs were primarily involved in the function of transcription, apoptotic process, and cell adhesion; and pathway of calcium, Wnt, and MAPK signaling. Real-time PCR verified exosomal miR-147 was downregulated, while miR-98-5p and miR-10a-5p were upregulated in SC-treated mice compared to asthma mice. Moreover, the target genes of miR-147-3p, miR-98-5p, and miR-10a-5p were mainly enriched in Wnt and MAPK inflammatory signaling. miR-10a-5p promoted the proliferation of mouse lung epithelial cells and downregulated the expression of Nfat5 and Map2k6. These data suggest SC-induced exosomal miRNAs might mediate the inflammatory signaling and might be involved in the SC treatment in asthma. The exosomal miRNAs might be promising candidates for the treatment of asthma.

2.
Drug Discov Today ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032705

RESUMO

Pharmacogenomics (PGx), studying the relationship between drug response and genetic makeup of an individual, is accelerating advances in precision medicine. The FDA includes PGx information in the labeling of approved drugs to better inform on their safety and effectiveness. We herein present a summary of PGx information found in 261 prescription drug labeling documents by querying the publicly available FDALabel database. A total of 362 drug-biomarker pairs (DBPs) were identified. We profiled DBPs using frequency of the biomarkers and their therapeutic classes. Four categories of applications (indication, safety, dosing and information) were discussed according to information in labeling. This analysis facilitates better understanding, utilization and translation of PGx information in drug labeling among researchers, healthcare professionals and the public.

3.
Phys Chem Chem Phys ; 22(9): 4880-4883, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32016184

RESUMO

Multiply-charged clusters with compact sizes that are stable in the gas phase are important due to their potential applications as weakly-coordinating ions and building blocks of bulk materials. However, the number of these clusters, especially those with high charge states beyond two, is limited. In this work, we show that gas-phase di- and tri-anions with record-high stability and compactness can be developed by utilizing a series of stable mono-anions with linear configurations as ligands. A stable di-anion with a record-high second electron binding energy of 6.26 eV and the smallest tri-anion with a record-low radius of 4.85 Å have been identified. This study demonstrates that multiply-charged clusters with highly charged state and compact sizes can be stabilized solely by selected terminal groups in the structure. This finding significantly enriches the database of stable multiply-charged gas-phase clusters and provides a path towards rational design of further multiply-charged species.

4.
Sci Rep ; 10(1): 2411, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051430

RESUMO

Soil erosion due to underground leakage is a major factor causing land degradation in karst regions. Rhizosphere effects (REs) on soil anti-erodibility (SAE) can alleviate this type of soil erosion by improving soil physical processes such as aggregate stability. However, the magnitudes and causes of interspecific variation in REs on SAE remain unclear. We tested the rhizosphere SAE indices of 42 key woody species distributed worldwide. Biologically active matter (BAM) and analogs of antibiotics (AOAs) that affect the SAE in rhizosphere soils were tested by gas chromatography-mass spectrometry (GC-MS). We then used principal component analysis (PCA) and redundancy analysis (RA) to establish a spectrum of interspecific variability in the REs for the first time. The spectrum shows a gradient of change among species. Eleven species exerted negative REs on the SAE, while the remaining species showed positive effects along the spectrum. The species with large positive effects were mostly deciduous, which have high contents of both BAM and total organic matter and low contents of AOAs in their rhizosphere soil; compared with the other species tested, these species also have more leaves and roots and are better adapted to barren soils. The botanical characteristics of species with negative REs on the SAE differed from those with large positive effects. The contents of BAM in the rhizosphere accounted for 16-23% of the total variation in REs on the SAE. This study quantified interspecific variation in REs and identified root exudates with negative REs.

6.
Acta Pharmacol Sin ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066885

RESUMO

Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics.

8.
Histopathology ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083752

RESUMO

AIMS: PDGFRB rearrangement defines a unique group of myeloid/lymphoid neoplasms with frequent eosinophilia and high sensitivity to tyrosine kinase inhibitors. This genetic abnormality is also rarely reported in Philadelphia-like B-lymphoblastic leukemia (B-ALL). PDGFRB rearrangement was initially thought to only occur in cases with 5q31-33 rearrangement by conventional cytogenetics; however, there are reported cases with cryptic rearrangements, suggesting the need for a broader screening strategy. METHODS AND RESULTS: We performed FISH for PDGFRB rearrangement in 197 patients, including 70 B-ALL, 10 myeloid neoplasms with 5q31-33 rearrangements, and 117 with eosinophilia (≥0.5 x 109 /L in peripheral blood or ≥ 5% in bone marrow), and identified PDGFRB rearrangement in 4/197 (2.0%) cases. In an attempt to identify clinicopathologic and genetic features that may have a stronger association with PDGFRB rearrangement, we analyzed 13 patients with confirmed PDGFRB rearrangements, including 10 myeloid neoplasms and 3 B-ALL. Of the 10 patients with myeloid neoplasms, eosinophilia was present in 8, monocytosis in 2, 5q31-33 rearrangement in 7, and abnormal bone marrow morphology in all. All patients with myeloid neoplasms showed an excellent response to imatinib including a patient in blast crisis. The three B-ALL patients presented de novo, showed no eosinophilia, had complex karyotype including 5q31-33 rearrangement, and had clinically aggressive courses with ultimate patient demise. CONCLUSIONS: These findings suggest a higher yield for the identification of PDGFRB rearrangement may result from an index of suspicion on patients with eosinophilia, monocytosis, bone marrow features of a myeloid neoplasm, 5q31-33 rearrangement, and patients with Philadelphia-like B-ALL.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31977971

RESUMO

To establish a continuous reinfusion of succus entericus and enteral nutrition (EN) in complex high-output fistula (HOF). Percutaneous puncture and catheterization technique was used to establish continuous reinfusion of succus entericus and EN in complex HOF. From May 2010 to June 2018, 21 patients with complex HOF used continuous reinfusion of succus entericus and EN. Six of them were completely cured, and 15 cases were cured after definitive surgery. Percutaneous puncture and catheterization technique was shown to be a useful and effective method for establishing continuous reinfusion of succus entericus and EN in patients with complex HOF. This method can prevent succus entericus loss and remove the barrier to implementing EN in HOF.

10.
Zhongguo Fei Ai Za Zhi ; 23(1): 5-14, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-31948532

RESUMO

BACKGROUND: Early investigation suggested patients' level of awareness regarding clinical trials was related with willingness to participation. This study was intended to evaluate the level of awareness of cancer patients regarding clinical trials and related influencing factors, and to compare the differences of awareness between patients who attended clinical trials before and not. METHODS: From Jun, 2018 to April, 2019, standardized question-naires were gathered from cancer patients (attended clinical trials vs not attended clinical trials) in our hospital regarding basic information and 10 other questions about awareness. The level of awareness was evaluated and patients were classified into "low cognition" and "high cognition" groups. Logistic regression analysis was performed to determine whether certain characteristics would predict for awareness. RESULTS: Of the 617 participants, 38.6% have attended clinical trials before. 338 (54.6%) patients had a correct overall understanding of clinical trials, while 44 (7.1%) patients still thought participants were the victim of scientific research. Except for the compensation of medical expenses (51.5% vs 48.7%) and related laws of clinical trials (52.3% vs 45.5%), other parts of understanding were elevated in patients attended clinical trials before comparing with patients who didn't, including significance (86.2% vs 77.6%), risk disclosure (91.2% vs 71.6%), confidentiality (73.2% vs 59.7%), voluntariness (95.8% vs 76.3%), withdrawal (86.6% vs 68.2%) and expenses (62.8% vs 39.2%). The proportion of participants who understand these components did not increase even in 239 patients who had attended clinical trials before. Participants who attended clinical trials before (OR=1.83, 95%CI: 1.11-3.00), unmarried/divorced (OR=5.04, 95%CI: 1.73-14.66), retired (OR=2.53, 95%CI: 1.16-5.50) had a higher level of awareness, while patients who had bad impression with doctors (OR=0.43, 95%CI: 0.26-0.72) had lower awareness. CONCLUSIONS: The current level of awareness for clinical trials of cancer patients in our hospital was relatively low, even in patients who had attended clinical trials before. It's necessary to improve patients' awareness of clinical trial by promoting harmony relationship between patients and doctors, as well as by enhancing related propagation. Strengthening the adequacy and efficacy of informed consent in clinical trials also needs to be achieved in the future.

11.
Zhongguo Fei Ai Za Zhi ; 23(1): 41-49, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-31948537

RESUMO

BACKGROUND: The clinical trials of new anti-tumor drugs are prospering in China. The acceptance of clinical trials in patients is an important factor affecting the speed and quality of clinical trials. Previous studies have investigated the acceptance of clinical trials in those cancer patients, who have never participated in a trial. This study is designed to investigate and compare the acceptance and related causes of clinical trials in cancer patients who have once participated in a clinical trial or not. METHODS: From June 2018 to April 2019, a standardized questionnaire-based survey was conducted among two groups of cancer patients classified by history of clinical trial participation in Cancer hospital, Chinese Academy of Medical Science, mainly focusing on their overall acceptance of clinical trials and related considerations, including the role of attending doctors, as well as group differences between the two participants. RESULTS: A total of 538 patients were enrolled with an average age of 53.5 years old, 51.1% of whom were males, and 43.3% of whom have never participated in a clinical trial. Overall, 502 patients (93.3%) were willing to or recommend their relatives or friends to participate in clinical trials, and patients with history of clinical trial participation had higher willingness (96.6% vs 90.8%, P=0.008). Patients were most likely to be motivated by expectation of optimal treatment (100.0% vs 99.3%) for both those who had once participated in a clinical trial or those not, respectively followed by financial burden reduction (56.0%) and recommendation by attending doctor (43.7%). The main reasons for unwillingness-to-participate for those who had once participated in a clinical trial were abandoning other treatment options, divided into control group or additional visits, while for those who had never participated in a clinical trial, ineffective treatment or serious adverse reactions were their main concerns. In the decision-making of clinical trial participation, 88% patients highly valued the role of recommendation by attending doctors. Among patients without trial participation history, 60.9% of those had no unwillingness-to-participate expressed that recommendation by attending doctors would change their decisions. The study also reported patients' preferences for information and access to clinical trials. CONCLUSIONS: The acceptance of clinical trials in cancer patients in our hospital is generally high, especially in patients who had a history of trial participation. It's of substantial significance to give full play to the role of doctors in improving the acceptance of clinical trials of cancer patients in China.

12.
Am J Clin Pathol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31977035

RESUMO

OBJECTIVES: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous category with a broad range of underlying genetic abnormalities. We investigated the significance of genetic factors in a large series of AML-MRC cases. METHODS: The morphologic findings, genetic data, and patient outcomes were assessed in 186 AML-MRC cases. RESULTS: The median overall survival (OS) was dismal in AML-MRC patients (median, 7.6 months; 95% confidence interval, 5-10.6 months). Karyotypically normal cases and cytogenetically abnormal cases without myelodysplastic syndrome (MDS)-related cytogenetic abnormalities showed similar OS, significantly better than cases carrying MDS-related cytogenetic abnormalities. MDS-related cytogenetic abnormalities, monosomal or complex karyotype, and history of MDS or myelodysplastic/myeloproliferative neoplasm were all associated with dismal outcome. CONCLUSIONS: AML-MRC predicts a poor prognosis. Our study supports the finding that the genetic profile plays a key role in determining prognosis in AML-MRC as defined according to the World Health Organization revised fourth edition (2017) diagnostic criteria.

13.
Gut ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900292

RESUMO

OBJECTIVE: High-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility. DESIGN: Faecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin. RESULTS: Transplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice. CONCLUSION: We revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes. TRIAL REGISTRATION NUMBER: NCT03634644.

14.
Biotechnol Bioeng ; 117(4): 945-958, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31930479

RESUMO

Reconstructing the chemical and structural characteristics of the plant cell wall represents a promising solution to overcoming lignocellulosic biomass recalcitrance to biochemical deconstruction. This study aims to leverage hydroxyproline (Hyp)-O-glycosylation, a process unique to plant cell wall glycoproteins, as an innovative technology for de novo design and engineering in planta of Hyp-O-glycosylated biopolymers (HypGP) that facilitate plant cell wall reconstruction. HypGP consisting of 18 tandem repeats of "Ser-Hyp-Hyp-Hyp-Hyp" motif or (SP4)18 was designed and engineered into tobacco plants as a fusion peptide with either a reporter protein enhanced green fluorescence protein or the catalytic domain of a thermophilic E1 endoglucanase (E1cd) from Acidothermus cellulolyticus. The engineered (SP4)18 module was extensively Hyp-O-glycosylated with arabino-oligosaccharides, which facilitated the deposition of the fused protein/enzyme in the cell wall matrix and improved the accumulation of the protein/enzyme in planta by 1.5-11-fold. The enzyme activity of the recombinant E1cd was not affected by the fused (SP4)18 module, showing an optimal temperature of 80°C and optimal pH between 5 and 8. The plant biomass engineered with the (SP4)18 -tagged protein/enzyme increased the biomass saccharification efficiency by up to 3.5-fold without having adverse impact on the plant growth.

15.
J Clin Lab Anal ; 34(2): e23043, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31556160

RESUMO

BACKGROUND: Early recognition and treatment for severe drug eruption are important in improving clinical outcomes. A few studies have reported laboratory parameters to evaluate the severity of drug eruptions. This study aimed to determine the association between serum ferritin and the severity of drug eruptions. METHODS: We retrospectively reviewed patients diagnosed with drug eruptions in our hospital from 2013 to 2018. RESULTS: We identified 85 patients (mean age 53.4 years), 20 in the severe cutaneous adverse drug reactions (SCADRs) group and 65 in the non-SCADRs group. Serum ferritin level was higher in the SCADRs group compared with that in the CADRs group (P<.001). Serum ferritin was positively associated with peripheral white blood cell count, aspartate aminotransferase level, alanine aminotransferase level, blood glucose level, blood creatinine level, and body temperature. Receiver operating characteristic (ROC) analysis revealed a good diagnostic value of ferritin (area under the curve [AUC]:0.87, 95% confidence interval [CI]:0.78-0.96) with a sensitivity of 80% and a specificity of 87.7% at a cutoff value of 416.15 ng/mL. CONCLUSIONS: Serum ferritin is significantly associated with the severity of CADRs and hence might be potentially used to evaluate the severity of CADRs.

16.
J Atheroscler Thromb ; 27(3): 255-270, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462616

RESUMO

AIM: Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism. METHODS: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague-Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082. RESULTS: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs. CONCLUSIONS: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.

17.
J Clin Lab Anal ; 34(1): e23016, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31423643

RESUMO

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a bone metabolism disorder involving systematic inflammation activation. Blood routine examination is easily available in clinical practice and contains abundant information reflecting the systematic inflammation level. Thus, it is attractive to achieve early diagnosis of PMOP and predict osteoporotic fracture risk just based on the biomarkers in blood routine examination. METHODS: A multi-centric prospective cohort study was designed and enrolled postmenopausal women from two independent institutions. All participants underwent the dual-energy X-ray absorptiometry (DEXA) scanning for diagnosing PMOP. Blood routine examination was conducted, and the key inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) were calculated. PMOP patients were followed up to observe osteoporotic fracture and identify the related risk predictors. RESULTS: A total of 92 participants out of 238 enrolled postmenopausal women were diagnosed with PMOP, with a prevalence of 38.66%. The main risk factors identified for PMOP included older age (OR = 2.06, 95% CI = 1.14-3.72), longer menopause duration (OR = 3.14, 95% CI = 2.06-4.79), higher NLR (OR = 2.11, 95% CI = 1.37-3.25), and higher SII (OR = 3.02, 95% CI = 1.98-4.61). Besides age and menopause duration, SII ≥834.89 was newly identified as a prominent risk factor for discriminating osteoporotic fracture risk in PMOP patients (HR = 3.66, 95% CI = 1.249-10.71). CONCLUSION: As an easy and economical biomarker calculated from blood routine examination, SII not only acts as a good risk predictor for PMOP diagnosis but also well discriminates the osteoporotic fracture risk, which deserves further investigation and application in clinical practice.

18.
Clin Rev Allergy Immunol ; 58(1): 71-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31147820

RESUMO

Adult-onset Still's disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology. AOSD is generally characterized by high spiking fever, arthralgia or arthritis, skin rash, leukocytosis, and hyperferritinemia. Traditionally, AOSD has been treated with non-steroidal anti-inflammatory drugs, corticosteroids, and immunosuppressants. An increasing number of studies have shown that proinflammatory cytokines, such as interleukin-1ß, -18, -6, and tumor necrosis factor-α, play key roles in AOSD and may serve as therapeutic targets. In the current review, we provided insights into the roles of these cytokines in the pathogenesis of AOSD and also provided a commentary on the clinical studies of biologic therapy against AOSD.

19.
Appl Neuropsychol Child ; 9(1): 41-55, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30526074

RESUMO

Objective: Attention-deficit/hyperactivity disorder C subtype (ADHD-C) is associated with social rejection and peer difficulties. The present study evaluates the comparative efficacy of group executive function training (GEFT) with social skills training (SST) in children with ADHD-C in China.Methods: A randomized, controlled treatment outcome study that comprised of 52 boys and 29 girls (age range: 9-12 years old) was conducted. The primary variable (peer relationship), secondary variables (executive functions [EFs] and social skills) and ADHD symptoms (inattention and hyperactive) were measured before and after the intervention and 3-month follow-up.Results: First, both GEFT and SST had instant effects on peer relationship. Second, GEFT mainly improved their EFs and self-control dimension of social skills. At the same time, ADHD symptoms were reduced. SST mainly improved their social skills, but had no effect on EFs and ADHD symptoms. Third, GEFT had better long-term effects than SST on peer relationship.Conclusion: Executive function training produced more effective and lasting changes on peer difficulties of ADHD children.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA