Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Eur Rev Med Pharmacol Sci ; 24(14): 7578, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32744683

RESUMEN

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis, by X.-J. Wei, X.-W. Li, J.-L. Lu, Z.-X. Long, J.-Q. Liang, S.-B. Wei, C.-X. Lu, W.-Z. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (17): 3886-3893-PMID: 28975975" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13351.

2.
Zhonghua Nei Ke Za Zhi ; 58(8): 560-565, 2019 Aug 01.
Artículo en Chino | MEDLINE | ID: mdl-31365976

RESUMEN

Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38℃) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2∶2∶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.


Asunto(s)
Antivirales/uso terapéutico , Ciclopentanos/uso terapéutico , Guanidinas/uso terapéutico , Gripe Humana/tratamiento farmacológico , Oseltamivir/uso terapéutico , Ácidos Carbocíclicos , Adolescente , Adulto , Anciano , Método Doble Ciego , Humanos , Gripe Humana/diagnóstico , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
3.
Sci Rep ; 9(1): 9373, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31253852

RESUMEN

Experiments on turbulence structures and features of a wind field under steady inflow and gusty wind inflows were implemented in a straight-through wind tunnel. Streamwise and wall-normal velocity components were measured using a streamline constant temperature anemometer (streamline CTA). Power spectra analyses revealed the existence of very large-scale motions (VLSMs) under both steady and gusty wind inflows; but new gusty scale motions (GSMs) were revealed under only gusty wind inflows. The GSMs might originate from an ordered external driving force that forces hairpin packets to align coherently in groups with a length scale related to the gust inflow condition. The streamwise wavelength of VLSMs is independent of inflow conditions, while the turbulent energy of VLSMs is associated with the wall-normal height and local mean streamwise velocity. In particular, the streamwise wavelength of GSMs increases linearly with the average value and period of sinusoidal gusty wind inflows, and the turbulent energy of GSMs is sensitive to the wall-normal height and all characteristic parameters of gusty wind inflows, including the average value, amplitude and period. Considerable wall-normal airflows induced by gusty wind inflows were detected and these are negatively correlated with the variation in gusty streamwise velocity, and root mean square (RMS) values of the gusty wall-normal velocity tended to increase linearly with the average value and amplitude of gusty wind inflows.

4.
Eur Rev Med Pharmacol Sci ; 21(17): 3886-3893, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28975975

RESUMEN

OBJECTIVE: STAT3 expression is elevated in the synovial tissue of patients with rheumatoid arthritis (RA). MiR-20a plays a role in mediating synovial inflammation in RA. Bioinformatics analysis has identified a binding site between miR-20 and the 3'-UTR of STAT3 mRNA. This study aimed to investigate the role of miR-20a in the regulation of STAT3 expression and synovial cell proliferation as well as apoptosis. PATIENTS AND METHODS: Synovial tissues were collected from RA patients and osteoarthritis (OA) patients to measure miR-20a, STAT3, p-STAT3, and Ki-67 expressions. Fibroblast-like synoviocytes (FLS) were treated with IL-17 (10 ng/ml) and then Ki-67 expression and cell cycle were evaluated by flow cytometry. The targeting relationship between miR-20a and STAT3 was assessed by dual luciferase reporter gene assay. FLS cells were divided into five groups: miR-NC, miR-20a mimic, si-NC, si-STAT3, and miR-20a mimic + si-STAT3 groups. RESULTS: In RA patients, significantly lower MiR-20a expression, and substantially higher STAT3, p-STAT3, and Ki-67 expression were found in the synovial tissues compared with those in OA patients. IL-17A treatment markedly promoted FLS cell proliferation, inhibited cell apoptosis, reduced miR-20a expression, as well as upregulated levels of STAT3, p-STAT3, and Bcl-2. MiR-20a played a regulatory function on the expression of STAT3. MiR-20a mimic and/or si-STAT3 transfection apparently downregulated STAT3, p-STAT3, and Bcl-2 expression, attenuated IL-17A-induced cell proliferation promotive and enhanced cell apoptosis in FLS cells. CONCLUSIONS: The expression of miR-20a was reduced in synovial tissue of RA patients with the increased level of STAT3. Downregulation of miR-20a promoted the expression of STAT3, p-STAT3, and Bcl-2, facilitated FLS cell proliferation, reduced apoptosis and, thereby, played a critical role in RA.


Asunto(s)
Apoptosis , Artritis Reumatoide/patología , Proliferación Celular , MicroARNs/metabolismo , Regiones no Traducidas 3' , Anciano , Antagomirs/metabolismo , Apoptosis/efectos de los fármacos , Artritis Reumatoide/genética , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Interleucina-17/farmacología , Antígeno Ki-67/metabolismo , Masculino , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Persona de Mediana Edad , Osteoartritis/genética , Osteoartritis/patología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Sinoviocitos/citología , Sinoviocitos/metabolismo
5.
Genet Mol Res ; 13(1): 2299-309, 2014 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-24737478

RESUMEN

The activity-regulated cytoskeletal associated protein (Arc/Arg3.1) has been implicated in experience-dependent synaptic plasticity and memory formation. However, information regarding its coding gene in buffalo remains scarce. In this study, the full-length of Arc/Arg3.1 was isolated and characterized (accession No. JX491649) and genetic variations of six river buffalo and eight swamp buffalo were investigated. A tissue expression profile was obtained using semi-quantitative reverse transcription-polymerase chain reaction. The coding region sequence of Arc/Arg3.1 contained 1191 nucleotides encoding a putative protein of 396 amino acids with a theoretical isoelectric point (pI) and molecular weight (Mw) of 5.4 and 45.2 kDa, respectively. Four polymorphisms (c.63T>C, c.228T>C, c.558G>A, and c.625G>C) were found in buffalo; however, only substitution c.625G>C was non-synonymous, leading to an amino acid change from Val to Leu at the 209th position of the Arc/Arg3.1 protein sequence. Bioinformatics analysis revealed that this substitution had no significant effect on Arc/Arg3.1 function (subPSEC = -1.4039, Pdeleterious = 0.1685), which indicated that Arc/Arg3.1 was highly conserved and functionally important in buffalo. Phylogenetic analysis revealed that the gene is closely related to that of Bos taurus and Bos grunniens. The gene was moderately expressed in the hypophysis and the placenta; it was weakly expressed in the kidney, milk, mammary gland, cerebrum, lung, heart, rumen, fat, and uterus; and it was almost silent in the muscle, liver, and skin. These findings will provide further insights into the structure and function of the immediate-early gene in buffalo.


Asunto(s)
Búfalos/genética , Proteínas del Citoesqueleto/genética , Perfilación de la Expresión Génica , Genes Inmediatos-Precoces , Proteínas del Tejido Nervioso/genética , Polimorfismo Genético , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Búfalos/clasificación , Bovinos , Proteínas del Citoesqueleto/química , Evolución Molecular , MicroARNs/genética , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/química , Especificidad de Órganos/genética , Filogenia , Polimorfismo de Nucleótido Simple , Interferencia de ARN , ARN Mensajero/genética , Alineación de Secuencia , Análisis de Secuencia de ADN
6.
J Appl Genet ; 51(1): 19-25, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20145296

RESUMEN

Fusarium head blight (FHB) is a destructive disease in wheat. The major quantitative trait locus (QTL) on 3BS from Sumai 3 and its derivatives has been used as a major source of the resistance to FHB worldwide, but the discrepancy in reported location of the major QTL could block its using in map based cloning and marker assisted selection. In this study, Chinese Spring-Sumai 3 chromosome 3B substitution line was used as resistant parent of the mapping population to reduce the confounded effect of genetic background in Sumai 3. The major QTL region was saturated with the Sequence Tagged Microsatellite (STM) and Sequence Tagged Site (STS) markers. A linkage map of chromosome 3B with 36 markers covering a genetic distance of 112.4 cM was constructed. Twelve new markers were inserted into the chromosome region where the major QTL was located. The average interval distance between markers was 1.5 cM. Multiple QTL Models (MQM) mapping indicated that the major QTL was located in the interval of Xgwm533-Xsts9-1, and explained 45.6% of phenotypic variation of the resistance to FHB. The SSR (simple sequence repeat) marker Xgwm533 and STM marker Xstm748tcac are closely linked to the major QTL.


Asunto(s)
Mapeo Cromosómico , Fusarium/genética , Inmunidad Innata/genética , Enfermedades de las Plantas/genética , Sitios de Carácter Cuantitativo , Triticum/genética , Cromosomas de las Plantas , Ligamiento Genético , Marcadores Genéticos , Enfermedades de las Plantas/microbiología
7.
Phytopathology ; 96(5): 534-41, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-18944314

RESUMEN

ABSTRACT Chinese Spring Sumai 3 chromosome 7A disomic substitution line (CS-SM3-7ADS) is highly resistant to Fusarium head blight (FHB), and an F(7) population of recombinant inbred lines derived from the cross CS-SM3-7ADS x Annong 8455 was evaluated for resistance to FHB to investigate main effects, epistasis, and environmental interactions of quantitative trait loci (QTLs) for FHB resistance. A molecular linkage map consists of 501 simple sequence repeat and amplified fragment length polymorphism markers. A total of 10 QTLs were identified with significant main effects on the FHB resistance using MapQTL and QTLMapper software. Among them, CS-SM3-7ADS carries FHB-resistance alleles at five QTLs on chromosomes 2D, 3B, 4D, and 6A. One QTL on 3BS had the largest effect and explained 30.2% of the phenotypic variance. Susceptible QTLs were detected on chromosomes 1A, 1D, 4A, and 4B. A QTL for enhanced FHB resistance was not detected on chromosome 7A of CS-SM3-7ADS; therefore, the increased FHB resistance in CS-SM3-7ADS was not due to any major FHB-resistance QTL on 7A of Sumai 3, but more likely was due to removal of susceptible alleles of QTLs on 7A of Chinese Spring. QTLMapper detected nine pairs of additive-additive interactions at 17 loci that explained 26% phenotypic variance. QTL-environment interactions explained 49% of phenotypic variation, indicating that the environments significantly affected the expression of the QTLs, especially these epistasis QTLs. Adding FHB-enhancing QTLs or removal of susceptible QTLs both may significantly enhance the degree of wheat resistance to FHB in a wheat cultivar.

8.
Aliment Pharmacol Ther ; 22(10): 927-34, 2005 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-16268966

RESUMEN

BACKGROUND: Melatonin is involved in the regulation of gastrointestinal motility and sensation. AIM: To determine the potential therapeutic effects of melatonin in irritable bowel syndrome (IBS). METHOD: Seventeen female patients satisfying the Rome II criteria for IBS were randomized to receive either melatonin 3 mg nocte or identically appearing placebo 1 nocte for 8 weeks, followed by a 4-week washout period and placebo or melatonin in the reverse order for another 8 weeks. Three validated questionnaires - the GI symptom, the sleep questionnaires and the Hospital Anxiety and Depression Scale - were used to assess symptom severity and to compute the IBS, sleep and anxiety/depression scores, respectively. RESULTS: Improvements in mean IBS scores were significantly greater after treatment with melatonin (3.9 +/- 2.6) than with placebo (1.3 +/- 4.0, P = 0.037). Percent response rate, defined as percentage of subjects achieving mild-to-excellent improvement in IBS symptoms, was also greater in the melatonin-treated arm (88% vs. 47%, P = 0.04). The changes in mean sleep, anxiety, and depression scores were similar with either melatonin or placebo treatment. CONCLUSIONS: Melatonin is a promising therapeutic agent for IBS. Its therapeutic effect is independent of its effects on sleep, anxiety or depression.


Asunto(s)
Fármacos Gastrointestinales/uso terapéutico , Síndrome del Colon Irritable/tratamiento farmacológico , Melatonina/uso terapéutico , Adulto , Anciano , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/etiología , Método Doble Ciego , Femenino , Humanos , Síndrome del Colon Irritable/complicaciones , Persona de Mediana Edad , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología , Encuestas y Cuestionarios
9.
Sci Total Environ ; 324(1-3): 247-59, 2004 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-15081710

RESUMEN

Air pollution in a metropolitan city like Hong Kong is a major obstacle to improve air quality and living environment due to the high population density and the vehicle emission increases. The high air pollutant levels impose harm to the human health and impair the city image. The characteristic analysis of air pollutants is very important and necessary to pollutant monitoring, forecasting and controlling. In this study, the interaction patterns of principle air pollutants, e.g. nitrogen dioxide (NO(2)), nitric oxide (NO), nitric oxides (NO(x)) and ozone (O(3)), a secondary pollutant, are investigated based on the measured database in four selected areas, which covers two urban types (i.e. residential area, mixed residential/commercial/industrial area) in Hong Kong, during the period of 1999-2001. The study involves analyzing the chemical and physical properties, the characteristics of air pollutants and the factors affecting such interactions using statistical method. The results reveal several routines in urban air pollutants' variations, interaction and trends from macro aspect.

10.
Environ Monit Assess ; 87(3): 235-54, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12952354

RESUMEN

As the health impact of air pollutants existing in ambient addresses much attention in recent years, forecasting of air pollutant parameters becomes an important and popular topic in environmental science. Airborne pollution is a serious, and will be a major problem in Hong Kong within the next few years. In Hong Kong, Respirable Suspended Particulate (RSP) and Nitrogen Oxides NOx and NO2 are major air pollutants due to the dominant diesel fuel usage by public transportation and heavy vehicles. Hence, the investigation and prediction of the influence and the tendency of these pollutants are of significance to public and the city image. The multi-layer perceptron (MLP) neural network is regarded as a reliable and cost-effective method to achieve such tasks. The works presented here involve developing an improved neural network model, which combines the principal component analysis (PCA) technique and the radial basis function (RBF) network, and forecasting the pollutant levels and tendencies based in the recorded data. In the study, the PCA is firstly used to reduce and orthogonalize the original input variables (data), these treated variables are then used as new input vectors in RBF neural network model established for forecasting the pollutant tendencies. Comparing with the general neural network models, the proposed model possesses simpler network architecture, faster training speed, and more satisfactory predicting performance. This improved model is evaluated by using hourly time series of RSP, NOx and NO2 concentrations collected at Mong Kok Roadside Gaseous Monitory Station in Hong Kong during the year 2000. By comparing the predicted RSP. NOx and NO2 concentrations with the actual data of these pollutants recorded at the monitory station, the effectiveness of the proposed model has been proven. Therefore, in authors' opinion, the model presented in the paper is a potential tool in forecasting air quality parameters and has advantages over the traditional neural network methods.


Asunto(s)
Contaminantes Atmosféricos/análisis , Modelos Teóricos , Redes Neurales de la Computación , Dióxido de Nitrógeno/análisis , Óxidos de Nitrógeno/análisis , Ciudades , Análisis Costo-Beneficio , Monitoreo del Ambiente/economía , Monitoreo del Ambiente/métodos , Predicción , Hong Kong , Tamaño de la Partícula , Sensibilidad y Especificidad
11.
Environ Monit Assess ; 79(3): 217-30, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12392160

RESUMEN

Air pollution has emerged as an imminent issue in modern society. Prediction of pollutant levels is an important research topic in atmospheric environment today. For fulfilling such prediction, the use of neural network (NN), and in particular the multi-layer perceptrons, has presented to be a cost-effective technique superior to traditional statistical methods. But their training, usually with back-propagation (BP) algorithm or other gradient algorithms, is often with certain drawbacks, such as: 1) very slow convergence, and 2) easily getting stuck in a local minimum. In this paper, a newly developed method, particle swarm optimization (PSO) model, is adopted to train perceptrons, to predict pollutant levels, and as a result, a PSO-based neural network approach is presented. The approach is demonstrated to be feasible and effective by predicting some real air-quality problems.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Redes Neurales de la Computación , Hong Kong , Tamaño de la Partícula
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 21(6): 881-5, 2001 Dec.
Artículo en Chino | MEDLINE | ID: mdl-12958922

RESUMEN

This paper introduces the backgrounds, principles and some popular algorithms used for resolving calibration transfer in multivariate calibration of chemometrics. The algorithms include S/B, DS, PDS, FIR, and Shenk's algorithm. The recent development of calibration transfer in the past two years is also reviewed. A number of key applications of different calibration transfer algorithms are summarized, which will be helpful for the further research of calibration transfer principles and algorithms. 51 references are cited.


Asunto(s)
Algoritmos , Simulación por Computador , Análisis Espectral/métodos , Calibración , Análisis de Fourier , Modelos Químicos , Modelos Teóricos , Análisis Multivariante , Procesamiento de Señales Asistido por Computador , Espectrofotometría Infrarroja
13.
Blood ; 83(12): 3682-8, 1994 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-8204892

RESUMEN

Although translocations of the BCL2 gene are frequent in B-cell non-Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B-cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B-CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI-HindIII fragment indicating a clustering of breakpoints. Two cases of B-CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms.


Asunto(s)
Leucemia de Células B/genética , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Translocación Genética , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 2 , Femenino , Humanos , Linfoma/genética , Masculino , Proteínas Proto-Oncogénicas c-bcl-2
15.
J Immunol ; 147(1): 86-95, 1991 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-2051030

RESUMEN

We have developed culture conditions for human lymphocytes that support primary in vitro immune responses to protein Ag of either human or nonhuman origin. We now show that these primed B cells can be efficiently immortalized by fusion with a heterohybrid fusion partner to generate human, Ag-specific IgM or IgG antibody-producing heterohybridomas at a rate of 17 to 50 hybrids/10(6) lymphocytes fused. Approximately 50% of the Ig-secreting clones were stable with respect to Ig secretion. Levels of secretion attained with terminal cultures ranged from less than 1 to 100 micrograms/ml. Fusions of cells between 2 and 5 days after initiation of in vitro exposure to Ag produced more Ag-reactive and Ag-specific antibodies than fusions at 1 day or fusions performed after 5 days. Ag-reactive hybrids could be isolated at frequencies of 3 to 10%, depending on antigenicity of the immunogen. Foreign proteins, horse spleen ferritin, and a murine monoclonal Ig, induced higher percentages of Ag-reactive mAb than immunization with the human-derived ferritin. Ag-reactive IgG mAb were produced at relatively high frequency, depending on immunization conditions and the nature of the Ag. The strategy for identification of the best hybrids included early elimination of unstable hybridomas and of hybridomas producing broadly cross-reactive antibody, followed by evaluation of units of Ag reactivity/micrograms Ig. Ferritin-specific mAb selected according to these criteria showed immunocytochemical reactivity with ferritin-containing tissues and apparent affinities in the range of 10(7) to 10(8)/mol.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Hibridomas/citología , Bazo/citología , Animales , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Monoclonales/metabolismo , Afinidad de Anticuerpos , Células Cultivadas , Ferritinas/inmunología , Caballos , Humanos , Técnicas In Vitro , Especificidad de la Especie , Bazo/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...