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6.
Clin Nutr ; 41(3): 620-629, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124469

RESUMO

BACKGROUND AND AIMS: Survival estimation for patients with spinal metastasis is crucial to treatment decisions. Psoas muscle area (PMA), a surrogate for total muscle mass, has been proposed as a useful survival prognosticator. However, few studies have validated the predictive value of decreased PMA in an Asian cohort or its predictive value after controlling for existing preoperative scoring systems (PSSs). In this study, we aim to answer: (1) Is PMA associated with survival in Han Chinese patients with spinal metastasis? (2) Is PMA a good prognosticator according to concordance index (c-index) and decision curve analysis (DCA) after controlling for six existing and commonly used PSSs? METHODS: This study included 180 adult (≥18 years old) Taiwanese patients with a mean age of 58.3 years (range: 22-85) undergoing surgical treatment for spinal metastasis. A patient's PMA was classified into decreased, medium, and large if it fell into the lower (0-33%), middle (33-67%), and upper (67-100%) 1/3 in the study cohort, respectively. We used logistic and cox proportional-hazard regressions to assess whether PMA was associated with 90-day, 1-year, and overall survival. The model performance before and after addition of PMA to six commonly used PSSs, including Tomita score, original Tokuhashi score, revised Tokuhashi score, modified Bauer score, New England Spinal Metastasis Score, and Skeletal Oncology Research Group machine learning algorithms (SORG-MLAs), was compared by c-index and DCA to determine if PMA was a useful survival prognosticator. RESULTS: Patients with a larger PMA is associated with better 90-day, but not 1-year, survival. The model performance of 90-day survival prediction improved after PMA was incorporated into all PSSs except SORG-MLAs. PMA barely improved the discriminatory ability (c-index, 0.74; 95% confidence interval [CI], 0.67-0.82 vs. c-index, 0.74; 95% CI, 0.66-0.81) and provided little gain of clinical net benefit on DCA for SORG-MLAs' 90-day survival prediction. CONCLUSIONS: PMA is a prognosticator for 90-day survival and improves the discriminatory ability of earlier-proposed PSSs in our Asian cohort. However, incorporating PMA into more modern PSSs such as SORG-MLAs did not significantly improve its prediction performance.


Assuntos
Músculos Psoas , Neoplasias da Coluna Vertebral , Adolescente , Adulto , Estudos de Coortes , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia
8.
Spine J ; 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35202784

RESUMO

BACKGROUND CONTEXT: Preoperative prediction of prolonged postoperative opioid prescription helps identify patients for increased surveillance after surgery. The SORG machine learning model has been developed and successfully tested using 5,413 patients from the United States (US) to predict the risk of prolonged opioid prescription after surgery for lumbar disc herniation. However, external validation is an often-overlooked element in the process of incorporating prediction models in current clinical practice. This cannot be stressed enough in prediction models where medicolegal and cultural differences may play a major role. PURPOSE: The authors aimed to investigate the generalizability of the US citizens prediction model SORG to a Taiwanese patient cohort. STUDY DESIGN: Retrospective study at a large academic medical center in Taiwan. PATIENT SAMPLE: Of 1,316 patients who were 20 years or older undergoing initial operative management for lumbar disc herniation between 2010 and 2018. OUTCOME MEASURES: The primary outcome of interest was prolonged opioid prescription defined as continuing opioid prescription to at least 90 to 180 days after the first surgery for lumbar disc herniation at our institution. METHODS: Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under the receiver operating characteristic curve and the area under the precision-recall curve), calibration, overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithm in the validation cohort. This study had no funding source or conflict of interests. RESULTS: Overall, 1,316 patients were identified with sustained postoperative opioid prescription in 41 (3.1%) patients. The validation cohort differed from the development cohort on several variables including 93% of Taiwanese patients receiving NSAIDS preoperatively compared with 22% of US citizens patients, while 30% of Taiwanese patients received opioids versus 25% in the US. Despite these differences, the SORG prediction model retained good discrimination (area under the receiver operating characteristic curve of 0.76 and the area under the precision-recall curve of 0.33) and good overall performance (Brier score of 0.028 compared with null model Brier score of 0.030) while somewhat overestimating the chance of prolonged opioid use (calibration slope of 1.07 and calibration intercept of -0.87). Decision-curve analysis showed the SORG model was suitable for clinical use. CONCLUSIONS: Despite differences at baseline and a very strict opioid policy, the SORG algorithm for prolonged opioid use after surgery for lumbar disc herniation has good discriminative abilities and good overall performance in a Han Chinese patient group in Taiwan. This freely available digital application can be used to identify high-risk patients and tailor prevention policies for these patients that may mitigate the long-term adverse consequence of opioid dependence: https://sorg-apps.shinyapps.io/lumbardiscopioid/.

9.
Nat Commun ; 13(1): 102, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013238

RESUMO

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/ .


Assuntos
Aminoácidos/química , Antineoplásicos/química , Software , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , /farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bases de Dados de Proteínas , Desenho de Fármacos/métodos , Humanos , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Ligação Proteica , Conformação Proteica em alfa-Hélice , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Relação Estrutura-Atividade
12.
Artigo em Inglês | MEDLINE | ID: mdl-34812197

RESUMO

STUDY DESIGN: An in vitro study to investigate the effect of pressure stimulation on nucleus pulposus (NP) cells. OBJECTIVE: The aim of this study was to investigate the question whether physical stimulation can be leveraged to enhance extracellular matrix (ECM) synthesis as a preventive measure for intervertebral disc (IVD) degeneration. SUMMARY OF BACKGROUND DATA: ECM plays an important role in regulating hydration and pressure balance of the IVD. METHODS: Cellular stimulation devices with different pressurizing protocols were used to create a pressurized environment to cells cultures. The setup was used to mimic the pressurized conditions within IVD to investigate the effect of pressure stimulation on NP cells. RESULTS: Pressure stimulation at 300 kPa can enhance the synthesis of ECM proteins Collagen II and aggrecan in NP cells and the effect of dynamic pressure stimulation outperformed the static one. The difference between static and dynamic pressure stimulation was due primarily to calcium signaling activated by pressure fluctuation. The superior effect of dynamic pressure holds for a wide range of stimulation durations, relating to the range of spontaneous calcium oscillations in NP cells. CONCLUSION: The results link mechanotransduction to the downstream ECM protein synthesis and suggest slow exercises that correspond with spontaneous calcium oscillations in NP cells can be effective to stimulate ECM synthesis in IVD.Level of Evidence: 4.

13.
Biol Lett ; 17(10): 20210388, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34610252

RESUMO

Anticipatory behaviour is the expectation of a near-future event based on information processed in the past and influences an animal's tactical decisions, particularly when there are significant fitness consequences. The grass lizard (Takydromus viridipunctatus) perches on blades of grass at night which likely reduces the probability of predation by terrestrial predators such as snakes, rodents and shrews. During twilight (starting 30 min before sunrise), they move from above the grass to within grass clumps and this is thought to afford the lizard protection while reducing detection by avian predators. Here, we examined how lizards shift their behaviour as a function of visual detectability to their primary predator, the cattle egret (Bubulcus ibis). We show that the lizards shift from their perch site during twilight at the earliest time at which egrets depart communal roosts. At the same time, visual modelling shows a dramatic increase in the detectability of the lizards to the visual system of egrets. Therefore, anticipatory behaviour in response to environmental cues acts to reduce predation risk as lizards become more conspicuous and predators become more active. Grass lizard anticipatory behaviour appears to be finely tuned by natural selection to adjust to temporal changes in predation risk.


Assuntos
Lagartos , Percas , Animais , Aves , Bovinos , Comportamento Predatório , Serpentes
14.
J Chin Med Assoc ; 84(12): 1084-1091, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561408

RESUMO

BACKGROUND: Statins, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been advocated by guidelines as secondary prevention medications to improve the long-term outcomes of post-acute myocardial infarction (AMI) patients. However, adequate drug adherence has always been challenging, and different treatment regimens may lead to divergent outcomes that remain unclear under current myocardial infarction (MI) care standards. This study investigated the association between use of different preventive regimens post-AMI and patients' long-term outcomes. METHODS: This cohort study used data files from the Taiwan National Health Insurance Research Database. A total of 77 520 people who were hospitalized with AMI between 2002 and 2015 were assessed. On the basis of medication possession ratio (MPR) to individual medications, eight treatment groups were examined in this study. Receiving therapy was defined as MPR ≥40%. We investigated the association between different treatment groups and all-cause mortality in 24 months. RESULTS: Overall, 51 322 patients with ST-elevation MI and 26 198 with non-ST-elevation MI were included in the study. Patients received all three preventive medications show the lowest mortality in 24 months follow-up periods among all treatment groups. Patients who did not usage of any of these three preventive medications had the highest mortality in 24 months (adjusted hazard ratio, 1.78; 95% CI, 1.64-1.93). This mortality rate had the same pattern across the three cohort generations (2002-2005, 2006-2010, and 2011-2015). CONCLUSION: In this large population-based real-world study, usage of three preventive therapies post-MI was associated with the lowest rate of all-cause mortality.


Assuntos
Doença Aguda , Quimioterapia Combinada , Infarto do Miocárdio/prevenção & controle , Alta do Paciente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan , Adulto Jovem
15.
PLoS One ; 16(8): e0255645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34347826

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) is currently the standard treatment for the prevention of ischemic events after stent implantation. However, the optimal DAPT duration remains elusive for patients with chronic kidney disease (CKD). Therefore, we aimed to compare the effectiveness and safety between long-term and short-term DAPT after coronary stenting in patients with CKD. METHODS: This retrospective cohort study analyze data from the Taipei Medical University (TMU) Institutional and Clinical Database, which include anonymized electronic health data of 3 million patients that visited TMU Hospital, Wan Fang Hospital, and Shuang Ho Hospital. We enrolled patients with CKD after coronary stenting between 2008 and 2019. The patients were divided into the long-term (>6 months) and short-term DAPT group (≤ 6 months). The primary end point was major adverse cardiovascular events (MACE) from 6 months after the index date. The secondary outcomes were all-cause mortality and Thrombolysis in Myocardial Infarction (TIMI) bleeding. RESULTS: A total of 1899 patients were enrolled; of them, 1112 and 787 were assigned to the long-term and short-term DAPT groups, respectively. Long-term DAPT was associated with similar risk of MACE (HR: 1.05, 95% CI: 0.65-1.70, P = 0.83) compare with short-term DAPT. Different CKD risk did not modify the risk of MACE. There was also no significant difference in all-cause mortality (HR: 1.10, 95% CI: 0.75-1.61, P = 0.63) and TIMI bleeding (HR 1.19, 95% CI: 0.86-1.63, P = 0.30) between groups. CONCLUSIONS: Among patients with CKD and coronary stenting, we found that long-term and short-term DAPT tied on the risk of MACE, all-cause mortality and TIMI bleeding.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Terapia Antiplaquetária Dupla/efeitos adversos , AVC Isquêmico/etiologia , AVC Isquêmico/prevenção & controle , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Stents Farmacológicos/efeitos adversos , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
Materials (Basel) ; 14(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206939

RESUMO

In this paper, we used two mass-produced industrial technologies, namely, thermal spraying and anodization methods, to enhance the surface characteristics of AISI 1045 medium carbon steel for use in special environments or products. The anodic film can effectively improve the surface properties of carbon steel. A sequence of treatments of the carbon steel substrate surface that consist of sandblasting, spraying the aluminum film, annealing, hot rolling, cleaning, grinding, and polishing can increase the quality of the anodized film. This paper proposes an anodization process for the surface of carbon steel to increase the corrosion resistance, hardness, color diversification, and electrical resistance. The resulting surface improves the hardness (from 170 HV to 524 HV), surface roughness (from 1.26 to 0.15 µm), coloring (from metal color to various colors), and corrosion resistance (from rusty to corrosion resistant). The electrochemical corrosion studies showed that the AISI 1045 steel surface with a hard anodized film had a lower corrosion current density of 10-5.9 A/cm2 and a higher impedance of 9000 ohm than those of naked AISI 1045 steel (10-4.2 A/cm2 and 150 ohm) in HCl gas.

17.
Nat Commun ; 12(1): 4404, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285225

RESUMO

Activation of fibroblasts is essential for physiological tissue repair. Uncontrolled activation of fibroblasts, however, may lead to tissue fibrosis with organ dysfunction. Although several pathways capable of promoting fibroblast activation and tissue repair have been identified, their interplay in the context of chronic fibrotic diseases remains incompletely understood. Here, we provide evidence that transforming growth factor-ß (TGFß) activates autophagy by an epigenetic mechanism to amplify its profibrotic effects. TGFß induces autophagy in fibrotic diseases by SMAD3-dependent downregulation of the H4K16 histone acetyltransferase MYST1, which regulates the expression of core components of the autophagy machinery such as ATG7 and BECLIN1. Activation of autophagy in fibroblasts promotes collagen release and is both, sufficient and required, to induce tissue fibrosis. Forced expression of MYST1 abrogates the stimulatory effects of TGFß on autophagy and re-establishes the epigenetic control of autophagy in fibrotic conditions. Interference with the aberrant activation of autophagy inhibits TGFß-induced fibroblast activation and ameliorates experimental dermal and pulmonary fibrosis. These findings link uncontrolled TGFß signaling to aberrant autophagy and deregulated epigenetics in fibrotic diseases and may contribute to the development of therapeutic interventions in fibrotic diseases.


Assuntos
Autofagia/genética , Epigênese Genética , Histona Acetiltransferases/metabolismo , Escleroderma Sistêmico/patologia , Fator de Crescimento Transformador beta/metabolismo , Adulto , Idoso , Animais , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Biópsia , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fibroblastos , Fibrose , Técnicas de Inativação de Genes , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Células NIH 3T3 , Cultura Primária de Células , Receptores de Fatores de Crescimento Transformadores beta , Transdução de Sinais/genética , Pele/citologia , Pele/patologia , Proteína Smad3/metabolismo , Adulto Jovem
18.
Global Spine J ; : 21925682211019692, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096362

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the factors contributing to the development of postoperative distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) with lowest instrumented vertebrae (LIV) at or above L1. METHODS: Patients with Lenke type 1 or 2 curves who underwent PSF with LIV at or above L1 with a minimum follow-up of 2 years were evaluated. The primary outcome measure was the occurrence of postoperative DJK. Radiographic parameters of sagittal alignment and inclusion/exclusion of sagittal stable vertebra (SSV) in PSF were analyzed to determine their associations with the occurrence of postoperative DJK. RESULTS: Overall, 122 patients (mean age: 15.1 ± 3.2 years) were included. The overall incidence of postoperative DJK was 6.6%. DJK was observed in 19.0% (8/42) of patients whose SSV was not included in PSF and not in patients with SSV included in PSF (n = 80). In the SSV-excluded group, univariate analysis found two significant risk factors for DJK: postoperative thoracic kyphosis (TK, T5-12) and postoperative thoracolumbar kyphosis (TLK, T11-L2). The ROC curve revealed that postoperative TK ≥ 25° and TLK ≥ 10° best predicted the occurrence of postoperative DJK in the SSV-excluded group. The incidence was significantly higher in cases with postoperative TK ≥ 25° or TLK ≥ 10° (7/13 = 53.8%) than in those with postoperative TK < 25° and TLK < 10° (1/29 = 3.4%). CONCLUSIONS: The current study revealed that postoperative TK ≥ 25° or postoperative TLK ≥ 10° with SSV excluded from PSF were related to DJK after PSF for Lenke type 1 and type 2 AIS. When the SSV is intended to be spared from PSF to save more motion segments, TK and TLK should be carefully evaluated and attained in a lesser magnitude (TK < 25°, TLK < 10°) after surgery.

19.
PLoS One ; 16(4): e0249940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831130

RESUMO

BACKGROUND: The optimal anticoagulant for end-stage renal disease patients for stroke prophylaxis is unknown. The efficacy and safety of warfarin in this population are debatable. In addition, real-world evidence of direct oral anticoagulants in patients with end-stage renal disease is limited. The aim of this study was to evaluate the clinical outcomes of rivaroxaban compared with warfarin in Taiwanese patients with end-stage renal disease with nonvalvular atrial fibrillation in a real-world setting. METHODS AND RESULTS: This was a retrospective population-based cohort study conducted using Taiwan's National Health Insurance Research Database. Patients with nonvalvular atrial fibrillation and end-stage renal disease who started on rivaroxaban or warfarin between February 2013 and September 2017 were eligible to participate in the study. The inverse probability of treatment weighting approach was used to balance baseline characteristics. Bleeding and thromboembolic outcomes were compared using competing risk analyses. The study population consisted of 3358 patients (173 and 3185 patients on rivaroxaban and warfarin, respectively). In the rivaroxaban group, 50.8%, 38.7%, and 10.4% of the patients received 10, 15, and 20 mg of the drug, respectively. The cumulative incidence of major bleeding was similar between the two groups; however, the gastrointestinal bleeding rate was lower in the rivaroxaban group (adjusted subdistribution hazard ratio [SHR]: 0.56, 95% confidence interval [CI]: 0.34-0.91) than in the warfarin group. Furthermore, the composite risk of ischemic stroke or systemic embolism was significantly lower in the rivaroxaban group (adjusted SHR: 0.36, 95% CI: 0.17-0.79). Similar findings were observed for patients who received 10 mg of rivaroxaban. CONCLUSIONS: In Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation, rivaroxaban may be associated with a similar risk of major bleeding but a lower risk of thromboembolism compared with warfarin. The potential benefit of 10 mg of rivaroxaban in this population requires further investigation.


Assuntos
Fibrilação Atrial/prevenção & controle , Hemorragia Gastrointestinal/epidemiologia , Falência Renal Crônica/tratamento farmacológico , Rivaroxabana/administração & dosagem , Tromboembolia/epidemiologia , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Taiwan , Tromboembolia/induzido quimicamente , Varfarina/efeitos adversos , Adulto Jovem
20.
Int J Mol Sci ; 22(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917452

RESUMO

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial-mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-ß) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-ß-induced EMT pathway.


Assuntos
Neoplasias Encefálicas/metabolismo , Fibronectinas/biossíntese , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Proteínas de Neoplasias/biossíntese , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Bases de Dados de Ácidos Nucleicos , Feminino , Fibronectinas/genética , Glioblastoma/diagnóstico , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Fator de Crescimento Transformador beta/genética
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