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2.
BMC Infect Dis ; 19(1): 966, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718584

RESUMO

BACKGROUND: Among pediatric patients hospitalized for Mycoplasma pneumoniae pneumonia (MPP), the risk factors for 90-day readmission after discharge is undefined. METHODS: We conducted a retrospective observational study of patients <14 years of age who were discharged with a diagnosis of MPP between January 2016 and February 2017. We collected clinical, laboratory and radiographic variables at the time of initial admission. We assessed pneumonia-related readmission within 90-day after discharge. Risk factors independently associated with rehospitalization were identified using multiple logistic regression models. RESULTS: Of the 424 MPP hospitalizations, 48 (11.3%) were readmitted within 90 days and were mainly diagnosed with pneumonia. Patients with younger age or coinfection with influenza A were more likely to be readmitted. In addition, compared with children without readmission, the readmission ones showed different clinical and laboratory characteristics at the index hospital admission. Multiple logistic regression analysis identified age (OR 0.815, 95%CI 0.706-0.940) and body temperature (OR 0.659, 95%CI 0.518-0.839) were significantly associated with lower risk of 90-day readmission. Coinfection with influenza was independently associated with a greater likelihood of 90-day readmission (OR 4.746, 95%CI 1.191-18.913). CONCLUSIONS: Readmission after MPP are common and is related to patients' age, body temperature and influenza A coinfection during initial hospital stay, indicating potential targets could be noticed to reduce the rehospitalization after pediatric MPP.

3.
Aging (Albany NY) ; 112019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31739286

RESUMO

Chronic cigarette smoke (CS) exposure induces prostate deficits. We previously found that swertiamarin had prostatic protective potential. This study was to investigate the possible protective effect of swertiamarin against CS-induced prostate dysfunction on human prostate epithelial cells, stromal cells and rats. Rat prostate collagen deposition and fibrosis were assessed by sirius red staining and measuring hydroxyproline content, as well as by qPCR and western blot analysis for fibrotic extracellular matrix components. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. In order to explore its underling mechanisms, the activities of Hedgehog signaling pathway and epithelial-mesenchymal transition of human prostate cells and rat prostate tissue were estimated. It was found that swertiamarin ameliorated CS-induced prostatic collagen deposition, relieved oxidative stress and local inflammation, inhibited the activation of Hedgehog signaling pathway and attenuated epithelial-mesenchymal transition. It indicated that swertiamarin could ameliorate CS-induced prostatic fibrosis by inhibiting epithelial-mesenchymal transition and Hedgehog pathway.

5.
Mar Biotechnol (NY) ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741169

RESUMO

The large yellow croaker Larimichthys crocea is an economically important marine fish species endemic to China and East Asia. Ningde area of Fujian Province is a major L. crocea aquaculture and spawning center in China. L. crocea cultivated at the Zhoushan area appears to be popular but suffered high mortality in cold water during winter seasons. To reduce the mortality rate, we pretreated fish with cold shocks prior to shift to cold water. In this study, we show that cold-pretreated L. crocea 12 days after shift to cold water increase the viability by 5.77-fold compared to the unpretreated (live fish 75 versus 13, p value = 1.775e-06, n = 100). The highest loss of 31 out of 100 fish in the unpretreated group occurred in day 3 after temperature shift. To identify the pretreatment-induced transcriptional changes that may be attributed to cold-resistance and survival, we performed RNA-seq analysis of a total of 48 fish that were prior to and 48 h, 54 h, and 72 h after temperature shift in pretreated and unpretreated groups in sextuplicate. Transcriptomic profiling analysis indicates that pretreatment-induced transcriptional alterations of enzymes involved in FASI, ß-oxidation, PUFA synthesis, oxidative phosphorylation, and molecular chaperones persisted after temperature shift, suggesting that these metabolic pathways may play a role in L. crocea cold-resistance and survival. Our study provides insights on how the pretreatment enhances the L. crocea growth fitness in cold water.

7.
J Surg Oncol ; 120(8): 1379-1385, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691290

RESUMO

BACKGROUND: Open surgery for hilar cholangiocarcinoma (HCCA) has already been widely reported and analyzed. However, the laparoscopic technique for treating HCCA remains controversial because of the lack of radicality and poor assessment of the resectability of hilar structures without direct palpation. The aim of this study was to provide detailed surgical procedures and photographs of this technically demanding operation, describe our experience in assessing resectability before and during surgery, and confirm the radicality of laparoscopic resection of Bismuth type III and IV HCCA. METHODS: From November 2016 to November 2018, nine patients received laparoscopic resection of Bismuth type III or IV HCCA in our department. RESULTS: Laparoscopic right hepatectomy was performed in four patients, and laparoscopic left hepatectomy was performed in five patients. Negative margins were achieved in all patients. Complications were found in two (22.22%) patients, with bile leakage and hepatic insufficiency each in one patient. The patient developing hepatic insufficiency had persistent and ongoing liver failure and finally expired. CONCLUSION: The radicality of laparoscopic resection for Bismuth type III and IV HCCA can be technically improved through extended lymphadenectomy, visual assessment of hilar structures, and frozen section techniques.

8.
Free Radic Biol Med ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31706990

RESUMO

Nitric oxide (NO) participates in many physiological and pathological processes in human. Urine tests tell a lot about health, which are convenient and harmless. Redox stress, including imbalance of reactive nitrogen species and its metabolites NOx, has been gaining increased attention in autism spectrum disorder (ASD) research. However, concentrations of urinary nitrite and nitrate among the ASD population stay unclear. In this study, nitrite and nitrate were precisely measured in urine specimens from 44 ASD children, 30 healthy children (the control group) and 28 healthy adults with an optimized and validated analytic method. For the first time, concentrations of urinary NOx in ASD and healthy children were reported. Nitrite in the ASD population is higher than in the control group, with concentrations of 0.8708 ±â€¯0.1121 µM (0.1556-3.0393 µM) and 0.5938 ±â€¯0.07276 µM (0.1134-2.1004 µM) (p = 0.0420), respectively. Nitrite in the adult groups is 0.5808 ±â€¯0.0985 µM (0.0808-1.9335 µM), which is similar to that in the control group. On the contrary, urinary nitrate concentration in ASD children is lower than that in the control group, which are 2.875 ±â€¯0.2716 mM (0.3264-7.1835 mM) and 4.558 ±â€¯0.5915 mM (1.1860-15.8555 mM) (p = 0.0133), respectively. Nitrate in adults is also significantly lower than that in the control, 2.799 ±â€¯0.3640 mM (0.2507-8.6978 mM) and 4.558 ±â€¯0.5915 mM (p = 0.0146), respectively. Nitrite/nitrate ratios for ASD and the control groups were 0.3496 ±â€¯0.04382 x 10-3 and 0.1604 ±â€¯0.01862 x 10-3 (p = 0.0002), which again indicated the probability of NOx as a novel biomarker. Furthermore, no correlation between NOx and gender, as well as sample collection timing was found. Taken together, the association between NOx and ASD was significant. Urinary nitrite, nitrate and NO2-/NO3-, might serve as a new biomarker for ASD diagnosis during pursuit of harmless, fast, and convenient diagnostic method. Further studies are needed for the metabolic pathways of NOx in ASD pathogenesis.

9.
Nanoscale ; 11(44): 21030-21045, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31674617

RESUMO

As a new kind of porous material, zeolitic imidazolate frameworks (ZIF-8) are built from zinc ions and 2-methylimidazolate and possess unique merits including high porosity, good structural regularity and tunability, adjustable surface functionality and intrinsic pH induced biodegradability. These advantages endow ZIF-8 with multiple functionalities and stimuli-responsive controlled release of loaded payloads by endogenous or exogenous means. In this review, we will summarize the recent advancement of ZIF-8 as nanocarriers for the loading of various molecules including chemotherapeutic drugs, photosensitizers, photothermal agents, and proteins to fabricate multifunctional nanocomposites for synergistic cancer therapy. In addition, the challenges and future developments in this area will be highlighted.

10.
Sci Rep ; 9(1): 15962, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685901

RESUMO

Fe-Mn-C-Al alloy is a new steel grade of TWIP steel developed in recent years. It has an excellent combination of elongation and tensile strength, as well as good anti-delayed fracture property. However, the crack sensitivity of this new TWIP steel has not been reported yet. In this study, differential thermal analysis (DTA) method was used, combined with professional thermodynamic software ThermoCalc to analyze the solidification behavior for Fe-Mn-C-Al alloys with different chemical compositions. Based on this, the crack sensitivity of TWIP steel is further determined. Through this study, it was found that Fe-Mn-C-Al TWIP steel may have a solidification sequence with high crack sensitivity, belonging to hypo-peritectic steel. Moreover, it was found that the carbon content has a large influence on the solidification behavior, and the manganese content also affects the solidification sequence. It can make the phase transition sequence of the solidification process change significantly, which may avoid the solidification behavior of hypo-peritectic reaction. The analysis results by thermodynamic software ThermoCalc are in good agreement with the experimental results. It displays thermoCalc can be a cost-effective way to develop Fe-Mn-C-Al TWIP steel. It is of great significance for shortening the development period of new Fe-Mn-C-Al steel grades.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31567715

RESUMO

BACKGROUND AND AIM: Open surgery remains the major approach to treat hepatocellular carcinoma, and laparoscopy-assisted liver resection has been recommended as a superior treatment. However, the efficacy of laparoscopic surgery versus open surgery for cirrhotic patients is under debate. Therefore, the aim of this meta-analysis was to compare the clinical outcomes of laparoscopic and open resection of hepatocellular carcinoma in patients with cirrhosis. METHODS: Electronic databases were searched for eligible literature updated on November 2018. After rigorous review of quality, the data were extracted from eligible trials. All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. RESULTS: Fourteen trials met the inclusion criteria. According to the pooled result of surgery duration, laparoscopic surgery was associated with significantly shorter hospital stay [STD mean difference (SMD) = -0.61, 95% confidence interval -0.89 to -0.32; P < 0.0001], lower intraoperative blood loss (SMD = -0.56, 95% confidence interval -0.99 to -0.12; P = 0.01), fewer complications (odds ratio = 0.38, 95% confidence interval 0.28 to 0.52; P < 0.00001) and lower transfusion rate (odds ratio = 0.58, 95% confidence interval 0.36-0.93; P = 0.02). Nevertheless, there was no remarkable difference in operative time (SMD = 0.17, 95% confidence interval -0.25 to -0.59; P = 0.42) between the two groups. The pooled analysis of overall survival showed that laparoscopic surgery did not achieve benefit compared with open surgery (P = 0.02). Moreover, the pooled results of three subgroups indicated that laparoscopic surgery was associated with significantly better disease-free survival (P < 0.05). CONCLUSION: The current analysis indicates that laparoscopic liver resection for hepatocellular carcinoma improved intraoperative and disease-free survival, with similar overall survival compared to the open procedure. Laparoscopic surgery may serve as a safe and feasible alternative for selected hepatocellular carcinoma patients with cirrhosis.

12.
Food Funct ; 10(11): 7262-7274, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31620755

RESUMO

Most current research on food-relevant Pickering emulsions has been conducted using inorganic or food-compatible organic particles as emulsifiers. A key challenge is maintaining a favourable structure while being able to resist displacement or destabilisation by surfactants and controlling transport of substrates during digestion. Liposome stabilised emulsions have demonstrated some potential for being smart, responsive delivery systems for poorly available bioactives and drugs. We developed a liposome-stabilized oil-in-water Pickering emulsion utilising macromolecular crowding- with polyethylene glycol (PEG). They were pH-controllable and had surfactant-dependent deformability whilst displaying dual delivery routes from both the liposome and oil phases. Dynamic light scattering, confocal microscopy and emulsion stability measurements indicated the liposomes containing 10% PEG at neutral pH remained intact at the interface for extended time. Various degrees of interfacial coverage still existed in the presence of PEG, under acidic environment and with added bile salts. Emulsions with added PEG maintained a more integrated structure after in vitro oral-gastric digestion, and showed greater lipolysis with more free fatty acids (14.7 ± 0.5% for with PEG vs. 12.7 ± 0.1% for without PEG) released during in vitro intestinal digestion. These Pickering emulsions could provide a flexible approach to controlled release under a broad range of conditions.

13.
Circulation ; 140(14): 1170-1184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31567014

RESUMO

BACKGROUND: Despite robust cholesterol lowering, cardiovascular disease risk remains increased in patients with diabetes mellitus. Consistent with this, diabetes mellitus impairs atherosclerosis regression after cholesterol lowering in humans and mice. In mice, this is attributed in part to hyperglycemia-induced monocytosis, which increases monocyte entry into plaques despite cholesterol lowering. In addition, diabetes mellitus skews plaque macrophages toward an atherogenic inflammatory M1 phenotype instead of toward the atherosclerosis-resolving M2 state typical with cholesterol lowering. Functional high-density lipoprotein (HDL), typically low in patients with diabetes mellitus, reduces monocyte precursor proliferation in murine bone marrow and has anti-inflammatory effects on human and murine macrophages. Our study aimed to test whether raising functional HDL levels in diabetic mice prevents monocytosis, reduces the quantity and inflammation of plaque macrophages, and enhances atherosclerosis regression after cholesterol lowering. METHODS: Aortic arches containing plaques developed in Ldlr-/- mice were transplanted into either wild-type, diabetic wild-type, or diabetic mice transgenic for human apolipoprotein AI, which have elevated functional HDL. Recipient mice all had low levels of low-density lipoprotein cholesterol to promote plaque regression. After 2 weeks, plaques in recipient mouse aortic grafts were examined. RESULTS: Diabetic wild-type mice had impaired atherosclerosis regression, which was normalized by raising HDL levels. This benefit was linked to suppressed hyperglycemia-driven myelopoiesis, monocytosis, and neutrophilia. Increased HDL improved cholesterol efflux from bone marrow progenitors, suppressing their proliferation and monocyte and neutrophil production capacity. In addition to reducing circulating monocytes available for recruitment into plaques, in the diabetic milieu, HDL suppressed the general recruitability of monocytes to inflammatory sites and promoted plaque macrophage polarization to the M2, atherosclerosis-resolving state. There was also a decrease in plaque neutrophil extracellular traps, which are atherogenic and increased by diabetes mellitus. CONCLUSIONS: Raising apolipoprotein AI and functional levels of HDL promotes multiple favorable changes in the production of monocytes and neutrophils and in the inflammatory environment of atherosclerotic plaques of diabetic mice after cholesterol lowering and may represent a novel approach to reduce cardiovascular disease risk in people with diabetes mellitus.

14.
Bioorg Med Chem Lett ; 29(20): 126665, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31495556

RESUMO

Pyruvate dehydrogenase kinases (PDKs) act as negative modulator of mitochondrial pyruvate dehydrogenase complex (PDC) and play a crucial role in the regulation of oxidative glycolysis, which recently have been considered as a potential drug target for varying types of cancer and diabetes. Herein, we describe the discovery and biological validation of novel anti-osteosarcoma therapeutics targeting PDK2. We identified 14 anti-osteosarcoma compounds from an in-house small molecule library, which were then evaluated in a PDK2 kinase inhibition assay. We found that compounds with 2-((4-oxo-6-((4-phenylpiperazin-1-yl)methyl)-4H-pyran-3-yl)oxy)acetamide moiety showed promising inhibitory potencies to PDK2. Especial for 12, which bound to PDK2 with a Kd value of 2.3 µM, and inhibited PDK2 activity with an EC50 value of 1.1 µM. In addition, 12 selectively inhibited PDK2, the selectivity indexes are 10.6, 22.0, and 60.9 for PDK2 as compared to PDK1, 2 and 4, respectively. The MTT assay suggested that 12 reduced MG-63 cancer cell proliferation with an IC50 value of 4.7 µM. All these observations indicated that 12 was a novel anti-osteosarcoma therapeutic, which deserved for further investigation.

15.
Mar Drugs ; 17(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484443

RESUMO

Phytoplankton are primary producers in the marine ecosystem, where phosphorus is often a limiting factor of their growth. Hence, they have evolved strategies to recycle phosphorus by replacing membrane phospholipids with phosphorus-free lipids. However, mechanisms for replacement of lipid classes remain poorly understood. To improve our understanding, we performed the lipidomic and transcriptomic profiling analyses of an oleaginous marine microalga Nannochloropsis sp. PJ12 in response to phosphorus depletion (PD) and replenishing. In this study, by using (liquid chromatography couple with tandem mass spectrometry) LC-MS/MS-based lipidomic analysis, we show that membrane phospholipid levels are significantly reduced upon PD, while phosphorus-free betaine lipid levels are increased. However, levels of phosphorus-free photosynthetic galactolipid and sulfolipid are not increased upon PD, consistent with the reduced photosynthetic activity. RNA-seq-based transcriptomic analysis indicates that enzymes involved in phospholipid recycling and phosphorus-free lipid synthesis are upregulated, supporting the lipidomic analysis. Furthermore, enzymes involved in FASII (type II fatty acid synthesis) elongation cycle upon PD are transcriptionally downregulated. EPA (eicosapentaenoic acid) level decrease upon PD is revealed by both GC-MS (gas chromatography coupled with mass spectrometry) and LC-MS/MS-based lipidomic analyses. PD-induced alteration is reversed after phosphorus replenishing. Taken together, our results suggest that the alteration of lipid classes upon environmental change of phosphorus is a result of remodeling rather than de novo synthesis in Nannochloropsis sp. PJ12.

16.
Int Immunopharmacol ; 76: 105882, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520991

RESUMO

Vitamin A (VA) is an anti-inflammatory agent that is important in modulating and balancing the immune system. The present study aimed to investigate the immunoregulatory effects of vitamin A supplement (VAS) in C57BL/6J mice infected with Plasmodium yoelii 17XL (P.y17XL) or Plasmodium berghei ANKA (P.bANKA). Following VA treatment, parasitaemia decreased, but survival rate did not significantly change during P.y17XL infection. However, in P.bANKA infected C57BL/6J mice, VA pretreatment decreased parasitaemia, and a lag in cerebral malaria (CM) was observed during the early stages of infection. Furthermore, VA pretreatment was also demonstrated to upregulate MHCII expression in dendritic cells (DCs), downregulate Th1 and Tregs, and downregulate TNF-α and IFN-γ production. The results of the current study indicated that VAS downregulated the inflammation response in CM, but did not exhibit an immunoregulatory effect against P.y17XL infection. VAS protected the onset of CM by reducing inflammation, and was also correlated with the downregulation of Th1 by modifying the function of DCs and Tregs. However, no significant effect was observed during P.y17XL infection.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31420655

RESUMO

Until recently, the polymyxin antibiotics were sparingly used due to dose limiting toxicities. However, the lack of therapeutic alternatives for infections caused by highly resistant Gram-negative bacteria has led to the increased use of the polymyxins. Unfortunately, in the last decade the world has witnessed increased rates of polymyxin resistance, which is likely in part due to its irrational use in human and veterinary medicine. The spread of polymyxin-resistance has been aided by the dissemination of the transferable polymyxin-resistance gene, mcr, in humans and the environment. The mortality of colistin-resistant bacteria infections varies in different reports. However, poor clinical outcome was associated with prior colistin treatment, illness severity, complications and multidrug resistance. Detection of polymyxin-resistance in the clinic is possible through multiple robust and practical tests including broth microdilution susceptibility testing, chromogenic agar testing, and molecular biology assays. There are multiple risk factors that increase a person's risk for infection with a polymyxin-resistant bacteria including age, prior colistin treatment, hospitalization and ventilator support. For patients that are determined to be infected by polymyxin-resistant bacteria, various antibiotic treatment options currently exist. The rising trend of polymyxin-resistance threatens patient care and warrants an effective control.

18.
J BUON ; 24(3): 1075-1080, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424663

RESUMO

PURPOSE: Breast cancer causes significant mortality in women world over. The lack of efficient and reliable biomarkers and therapeutic targets impedes the treatment of breast cancer. Herein, the role and therapeutic potential of miR-155 was investigated in different breast cancer cell lines Methods: Cell viability was determined by WST-1 and colony formation assays. Transfections were performed by Lipofectamine 2000 reagent. Cell cycle analysis was carried out by flow cytometry and apoptosis was detected by AO (acridine orange)/EB (ethidium bromide) staining. Cell migration and cell invasion were determined by wound healing assay. RNA and protein expressions were determined by qRT-PCR and western blotting, respectively. RESULTS: miR-155 was significantly upregulated in all the breast cancer cells. Suppression of miR-155 in SK-BR-3 cells inhibited the growth and colony formation. The inhibition of SK-BR-3 cell proliferation was found to trigger apoptotic cell death and cell cycle arrest. Induction of apoptosis was also accompanied with enhancement of cytochrome c, Bax caspase 3, 8 and 9and inhibition of Bcl-2. Besides, suppression of miR-155 resulted in the decrease of cell migration and invasion. Bioinformatic analysis revealed MAPK7 to be the potential target of miR-155. The MAPK7 expression was also upregulated in all the breast cancer cells and suppression of miR-155 resulted in its downregulation. CONCLUSION: Taken together, miR-155 may prove essential in the management of breast cancer.

19.
Org Lett ; 21(16): 6418-6422, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31368713

RESUMO

An attractive method for the synthesis of indoline-7-carboxylates through RhCl3-catalyzed C-H carbonylation of indolines with CO and alcohols was developed. The copper-based oxidant and removable pyrimidyl directing group played important roles in achieving high-level yields of the title products. Based on control experiments, a possible catalytic cycle was proposed.

20.
J Natl Cancer Inst ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400201

RESUMO

BACKGROUND: Isocitrate dehydrogenase (IDH)-wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, while only 27% of IDH-WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood. METHODS: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests. RESULTS: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knockdown or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; HR = 3.94 (95%CI=1.87-8.28), p<.001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, p=.03), which decreased dramatically after surgery. CONCLUSION: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.

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