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OBJECTIVES: To reduce the overuse of magnetic resonance cholangiopancreatography and the rates of non-therapeutic endoscopic retrograde cholangiopancreatography in pediatric patients suspected of choledocholithiasis. MATERIALS AND METHODS: Retrospective study of patients suspected of choledocholithiasis between January 2010 and June 2023. Patients with cholangitis or two or more of the following predictive factors of choledocholithiasis in initial laboratory tests and ultrasound were categorized as high-risk group: total bilirubin level ≥ 2 mg/dl, common bile duct > 6 millimeters on ultrasound; and detection of choledocholithiasis by ultrasound. Patients were recategorized according to the results of the second set of laboratory and ultrasound analysis. Confirmatory modalities (magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, and/or intraoperative cholangiography) were used to evaluate the presence of choledocholithiasis. Finally, we assessed the predictive capability of both the initial high-risk group and the group after recategorization. RESULTS: A total of 129 patients were included. After initial studies, 72 (55.8%) patients were classified into the high-risk group. After recategorization, only 29 (22.5%) patients were included in this group. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the initial high-risk group were 89.3%, 53.5%, 34.7%, 94.7%, and 61.2%, respectively, while after recategorization, they were 82.1%, 94.1%, 79.3%, 95.0%, and 91.5%, respectively. CONCLUSIONS: Recategorization of the risk of choledocholithiasis would significantly improve the diagnostic accuracy of choledocholithiasis and help reduce the overuse of more complex and unnecessary studies/procedures.
OBJETIVOS: Disminuir la sobre indicación de la colangiorresonancia y las tasas de colangiopancreatografía retrógrada endoscópica o terapéuticas en pacientes pediátricos con sospecha de coledocolitiasis. MATERIAL Y METODOS: Estudio retrospectivo de pacientes con sospecha de coledocolitiasis entre enero de 2010 y junio de 2023. Los pacientes con colangitis o dos o más de los siguientes factores predictivos de coledocolitiasis en las pruebas de laboratorio y ecografía iniciales, se categorizaron como grupo de alto riesgo: nivel de bilirrubina total ≥ 2 mg/dl, colédoco > 6 milímetros en ecografía; y la detección de coledocolitiasis por ecografía. Los pacientes fueron recategorizados de acuerdo a los resultados del segundo conjunto de análisis de laboratorio y ecografía. Para evaluar la presencia de coledocolitiasis se utilizaron modalidades confirmatorias (colangiorresonancia, colangiopancreatografía retrógrada endoscópica y/o colangiografía intraoperatoria). Finalmente, evaluamos la capacidad predictiva tanto del grupo de alto riesgo inicial como del grupo después de la recategorización. RESULTADOS: Se incluyeron 129 pacientes. Luego de los estudios iniciales, 72 (55,8%) pacientes se clasificaron en el grupo de alto riesgo. Luego de la recategorización, solo 29 (22,5%) pacientes fueron incluidos dentro de este grupo. La sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y precisión diagnóstica del grupo de alto riesgo inicial fueron de 89,3%, 53,5%, 34,7%, 94,7% y 61,2%, mientras que luego de la recategorización fueron de 82,1%, 94,1%, 79,3%, 95,0% y 91,5%, respectivamente. CONCLUSIONES: La recategorización del riesgo de coledocolitiasis, mejoraría significativamente la precisión diagnóstica de coledocolitiasis y ayudaría a disminuir la sobre indicación de estudios/procedimientos complejos e innecesarios.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Coledocolitiasis , Humanos , Coledocolitiasis/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Niño , Preescolar , Pancreatocolangiografía por Resonancia Magnética/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Ultrasonografía/métodos , Adolescente , Cálculos Biliares , Lactante , Valor Predictivo de las Pruebas , Colangitis/diagnóstico , Bilirrubina/sangre , Factores de RiesgoRESUMEN
Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) intervals that best predict the concentration of adulterants in cocaine samples. Wavelengths are ranked according to their relevance through ReliefF and mRMR feature selection approaches, and an iterative process removes less relevant wavelengths based on the ranking suggested by each approach. Gaussian Process (GP) regression models are constructed after each wavelength removal and the prediction performance is evaluated using RMSE. The subset balancing a low RMSE value and a small percentage of retained wavelengths is chosen. The proposed framework was validated using a dataset consisting of 345 samples of cocaine with different amounts of levamisole, caffeine, phenacetin, and lidocaine. Averaged over the four adulterants, the GP regression coupled with the mRMR retained 1.07â¯% of the 662 original wavelengths, outperforming PLS and SVR regarding prediction performance.
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Cocaína , Contaminación de Medicamentos , Cocaína/análisis , Contaminación de Medicamentos/prevención & control , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Distribución Normal , Cafeína/análisis , Levamisol/análisis , Fenacetina/análisis , Análisis de RegresiónRESUMEN
INTRODUCTION AND OBJECTIVES: Lung cancer is the second type of cancer with the second highest incidence rate and the first with the highest mortality rate in the world. Machine learning through the analysis of imaging tests such as positron emission tomography/computed tomography (PET/CT) has become a fundamental tool for the early and accurate detection of cancer. The objective of this study was to propose an image analysis architecture (PET/CT) ordered in phases through the application of ensemble or combined machine learning methods for the early detection of lung cancer by analyzing PET/CT images. MATERIAL AND METHODS: A retrospective observational study was conducted utilizing a public dataset entitled "A large-scale CT and PET/CT dataset for lung cancer diagnosis." Various imaging modalities, including CT, PET, and fused PET/CT images, were employed. The architecture or framework of this study comprised the following phases: 1. Image loading or collection, 2. Image selection, 3. Image transformation, and 4. Balancing the frequency distribution of image classes. Predictive models for lung cancer detection using PET/CT images included: a) the Stacking model, which used Random Forest and Support Vector Machine (SVM) as base models and complemented them with a logistic regression model, and b) the Boosting model, which employed the Adaptive Boosting (AdaBoost) model for comparison with the Stacking model. Quality metrics used for evaluation included accuracy, precision, recall, and F1-score. RESULTS: This study showed a general performance of 94% with the Stacking method and a general performance of 77% with the Boosting method. CONCLUSIONS: The Stacking method proved to be a model with high performance and quality for lung cancer detection when analyzing PET/CT images.
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Neoplasias Pulmonares , Aprendizaje Automático , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Pulmonares/diagnóstico por imagen , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , MasculinoRESUMEN
In this work, we report the structural analysis of Cu+ and Cu2+ ions in zeolite as a nanoreactor with antibacterial applications. A simple one-step process was implemented to obtain Cu ions in zeolite A (ZA4) by controlling the temperature in the solutions to guarantee the ions' stability. Samples were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy, showing the characteristic zeolite elements as well as the characteristic bands with slight modifications in the chemical environment of the zeolite nanoreactor attributed to Cu ions by FT-IR spectroscopy. In addition, a shift of the characteristic peaks of ZA4 in X-ray diffraction was observed as well as a decrease in relative peak intensity. On the other hand, the antibacterial activity of Cu ions in the zeolite nanoreactor was evaluated.
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Understanding the factors that influence fire regimes in Mediterranean climates is essential to reduce their risk. This research uses Climate Hazards Group InfraRed Precipitation with Station (CHIRPS) and Moderate-Resolution Imaging Spectroradiometer (MODIS) satellite resources to evaluate recent changes in land surface temperature, precipitation, and vegetation and their effects in the occurrence of large fires in the Mediterranean Basin. The results of the analysis of 335 fire events occurred in southern Spain from 2001 to 2020 show an increase in hazardous meteorological factors linked to droughts and thermal anomalies. The study also examines the potential of preserving traditional landscapes to minimize such risk. In fact, the maintenance and recovering of traditional agro-pastoral activities is an effective option to reduce flammability and increase the resilience of cultural landscapes in hazardous climatic conditions.
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Urban green areas minimize the negative effects of climatic change and improve the sustainability of historic cities. Despite this, green areas have traditionally been considered a threat to heritage buildings because they cause humidity changes, that accelerate degradation processes. Within this context, this study evaluates the trends in the inclusion of green areas in historic cities and the effects it causes on humidity and conservation of earthen fortifications. To achieve this goal, vegetative and humidity information has been obtained since 1985 from Landsat satellite images. The historical series of images has been statistically analysed in Google Earth Engine to obtain maps that show the means, 25th, and 75th percentiles of the variations registered in the last 35 years. The results allow visualizing spatial patterns and plotting the seasonal and monthly variations. In the decision-making process, the proposed method allows to monitor whether the presence of vegetation is an environmental degradation agent in the nearby earthen fortifications.The analysis of the historic fortified cities of Seville and Niebla (Spain) shows a gradual increase in green areas and an interest in locating them near the earthen fortifications. The impact on the fortifications is specific to each type of vegetation and can be positive or negative. In general, the low humidity registered indicates low danger, and the presence of green areas favours drying after heavy rains. This study suggests that increasing green spaces to historic cities does not necessarily endanger the preservation of earthen fortifications. Instead, managing both heritage sites and urban green areas together can encourage outdoor cultural activities, reduce the impacts of climate change, and enhance the sustainability of historic cities.
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OBJECTIVE: To assess the efficacy of the endourological treatment of ectopic ureterocele in children in a large series and with a long-term follow-up. MATERIALS AND METHODS: A retrospective, descriptive study of patients with ectopic ureterocele who had undergone surgery in our institution in the last 15 years was carried out. All patients were treated using an endourological approach, both for ureterocele and postoperative vesicoureteral reflux (VUR). RESULTS: 40 patients were treated -55% with left involvement and 5% with bilateral involvement. Mean age at diagnosis was 4.97 months, with diagnosis being established prenatally in 54.1% of cases. In all patients but one, endourological puncture of the ureterocele was conducted. Mean age at surgery was 6.96 months (0-1.11). Surgery was performed on an outpatient basis in 94.9% of patients. No perioperative complications were recorded. In the last 30 patients, preoperative voiding cystourethrography was not carried out. 72.5% of patients had postoperative VUR (44.8% into the upper pyelon, 10.3% into the lower pyelon, 17.2% into both, 6.9% into the contralateral system, and 20.7% into the bilateral system), but it was resolved with a single endoscopic procedure in 48.1% of cases (65% of patients were healed with two procedures). VUR was not endoscopically resolved in 3 patients who required ureteral re-implantation. 6 patients required heminephrectomy (n=3) or nephrectomy (n=3) as a result of functional impairment and infections. CONCLUSION: The endourological treatment of ectopic ureterocele is a little aggressive and little invasive technique that allows the obstruction to be resolved on an outpatient basis, which means bladder surgery -if required- can be performed outside the neonatal period.
OBJETIVO: Evaluar la eficacia del tratamiento endourológico del ureterocele ectópico en niños en una serie amplia y con seguimiento a largo plazo. MATERIAL Y METODOS: Estudio retrospectivo descriptivo de los pacientes con ureterocele ectópico intervenidos en nuestro centro en los últimos 15 años. Todos los pacientes se tratan por vía endourológica, tanto el ureterocele como el reflujo vesicoureteral (RVU) postoperatorio. RESULTADOS: Se trataron 40 pacientes, 55% eran izquierdos y 5% bilaterales. La edad media al diagnóstico fue de 4,97 meses siendo de diagnóstico prenatal el 54,1%. En todos los pacientes menos uno se realizó una punción endourológica del ureterocele. La edad media en el momento de la cirugía era de 6,96 meses (0-1,11). La cirugía fue ambulante en un 94,9% de los pacientes. No se registraron complicaciones perioperatorias. En los últimos 30 pacientes no se realizó cistouretrografía miccional preoperatoria. Un 72,5% de los pacientes presentaron RVU postoperatorio (44,8% a pielón superior, 10,3% a pielón inferior, 17,2% a ambos, 6,9% al sistema contralateral y 20,7% bilateral), pero este se resolvió con un único procedimiento endoscópico en un 48,1% de los casos (curación del 65% de los pacientes con dos procedimientos). El RVU no se resolvió de forma endoscópica en 3 pacientes que requirieron un reimplante ureteral. Seis pacientes precisaron heminefrectomía (n= 3) o nefrectomía (n= 3) por anulación funcional e infecciones. CONCLUSION: El tratamiento endourológico del ureterocele ectópico es una técnica poco agresiva invasiva que consigue la resolución de la obstrucción de forma ambulante permitiendo diferir la cirugía vesical (si fuera necesaria) fuera del periodo neonatal.
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Uréter , Ureterocele , Reflujo Vesicoureteral , Niño , Recién Nacido , Humanos , Lactante , Ureterocele/complicaciones , Ureterocele/diagnóstico , Ureterocele/cirugía , Estudios Retrospectivos , Endoscopía/efectos adversos , Procedimientos Quirúrgicos Urológicos , Resultado del Tratamiento , Reflujo Vesicoureteral/complicacionesRESUMEN
Objetivo: Evaluar la eficacia del tratamiento endourológico delureterocele ectópico en niños en una serie amplia y con seguimientoa largo plazo. Material y métodos: Estudio retrospectivo descriptivo de los pacientes con ureterocele ectópico intervenidos en nuestro centro en losúltimos 15 años. Todos los pacientes se tratan por vía endourológica,tanto el ureterocele como el reflujo vesicoureteral (RVU) postoperatorio. Resultados: Se trataron 40 pacientes, 55% eran izquierdos y 5%bilaterales. La edad media al diagnóstico fue de 4,97 meses siendo dediagnóstico prenatal el 54,1%. En todos los pacientes menos uno serealizó una punción endourológica del ureterocele. La edad media enel momento de la cirugía era de 6,96 meses (0-1,11). La cirugía fue ambulante en un 94,9% de los pacientes. No se registraron complicacionesperioperatorias. En los últimos 30 pacientes no se realizó cistouretrografía miccional preoperatoria. Un 72,5% de los pacientes presentaron RVUpostoperatorio (44,8% a pielón superior, 10,3% a pielón inferior, 17,2%a ambos, 6,9% al sistema contralateral y 20,7% bilateral), pero este seresolvió con un único procedimiento endoscópico en un 48,1% de loscasos (curación del 65% de los pacientes con dos procedimientos). ElRVU no se resolvió de forma endoscópica en 3 pacientes que requirieronun reimplante ureteral. Seis pacientes precisaron heminefrectomía (n= 3)o nefrectomía (n= 3) por anulación funcional e infecciones. Conclusión: El tratamiento endourológico del ureterocele ectópicoes una técnica poco agresiva invasiva que consigue la resolución de laobstrucción de forma ambulante permitiendo diferir la cirugía vesical(si fuera necesaria) fuera del periodo neonatal.(AU)
Objective: To assess the efficacy of the endourological treatmentof ectopic ureterocele in children in a large series and with a long-termfollow-up. Materials and methods: A retrospective, descriptive study ofpatients with ectopic ureterocele who had undergone surgery in ourinstitution in the last 15 years was carried out. All patients were treatedusing an endourological approach, both for ureterocele and postoperativevesicoureteral reflux (VUR). Results: 40 patients were treated 55% with left involvement and5% with bilateral involvement. Mean age at diagnosis was 4.97 months,with diagnosis being established prenatally in 54.1% of cases. In allpatients but one, endourological puncture of the ureterocele was conducted. Mean age at surgery was 6.96 months (0-1.11). Surgery wasperformed on an outpatient basis in 94.9% of patients. No perioperativecomplications were recorded. In the last 30 patients, preoperative voidingcystourethrography was not carried out. 72.5% of patients had postoper-ative VUR (44.8% into the upper pyelon, 10.3% into the lower pyelon,17.2% into both, 6.9% into the contralateral system, and 20.7% into thebilateral system), but it was resolved with a single endoscopic procedurein 48.1% of cases (65% of patients were healed with two procedures).VUR was not endoscopically resolved in 3 patients who required ureteral remplantation. 6 patients required heminephrectomy (n=3) ornephrectomy (n=3) as a result of functional impairment and infections. Conclusion: The endourological treatment of ectopic ureterocele isa little aggressive and little invasive technique that allows the obstructionto be resolved on an outpatient basis, which means bladder surgery ifrequired can be performed outside the neonatal period.(AU)
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Humanos , Masculino , Femenino , Lactante , Ureterocele , Endoscopía , Pediatría , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Epidemiología DescriptivaRESUMEN
We investigate the structural relaxation of a soft-sphere liquid quenched isochorically (Ï = 0.7) and instantaneously to different temperatures Tf above and below the glass transition. For this, we combine extensive Brownian dynamics simulations and theoretical calculations based on the non-equilibrium self-consistent generalized Langevin equation (NE-SCGLE) theory. The response of the liquid to a quench generally consists of a sub-linear increase of the α-relaxation time with system's age. Approaching the ideal glass-transition temperature from above (Tf > Ta), sub-aging appears as a transient process describing a broad equilibration crossover for quenches to nearly arrested states. This allows us to empirically determine an equilibration timescale teq(Tf) that becomes increasingly longer as Tf approaches Ta. For quenches inside the glass (Tf ≤ Ta), the growth rate of the structural relaxation time becomes progressively larger as Tf decreases and, unlike the equilibration scenario, τα remains evolving within the whole observation time-window. These features are consistently found in theory and simulations with remarkable semi-quantitative agreement and coincide with those revealed in a previous and complementary study [P. Mendoza-Méndez et al., Phys. Rev. 96, 022608 (2017)] that considered a sequence of quenches with fixed final temperature Tf = 0 but increasing Ï toward the hard-sphere dynamical arrest volume fraction ÏHS a=0.582. The NE-SCGLE analysis, however, unveils various fundamental aspects of the glass transition, involving the abrupt passage from the ordinary equilibration scenario to the persistent aging effects that are characteristic of glass-forming liquids. The theory also explains that, within the time window of any experimental observation, this can only be observed as a continuous crossover.
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Vidrio , Simulación de Dinámica Molecular , Temperatura , Temperatura de Transición , Vidrio/químicaRESUMEN
BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.
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Neoplasias , Enfermedades no Transmisibles , Refugiados , Sistemas de Socorro , Humanos , Masculino , Femenino , Niño , Naciones Unidas , Atención a la Salud , Neoplasias/epidemiologíaRESUMEN
INTRODUCTION: Ectopic scrotum is a rare clinical entity, potentially associated with other congenital abnormalities. We present the case of a patient with buried penis secondary to ectopic scrotum. The surgical technique was described, and a literature review was carried out. CLINICAL CASE: 1-year-old patient with ectopic right hemiscrotum and the testes within the scrotal sac. A double Z-plasty was performed with two flaps - one above the penis, surrounding the ectopic scrotum, and the other one at the scrotum to modify the bifid scrotum. The upper flap was rotated downwards, which allowed ectopy to be repaired, and the lower flap was used to repair bifidity. No postoperative complications were recorded. Follow-time was 6 months, with good final cosmetic results. DISCUSSION: Ectopic scrotum is an infrequent congenital malformation. Cutaneous rotation flaps with Z-plasties are a valid treatment option, with good long-term cosmetic results.
INTRODUCCION: La ectopia escrotal constituye una entidad clínica rara, que puede asociar otras anomalías congénitas. Presentamos el caso de un paciente con un pene oculto secundario a una ectopia escrotal, con descripción de la técnica quirúrgica y revisión de la literatura. CASO CLINICO: Paciente de un año de vida que presentaba un hemiescroto derecho ectópico con testes en bolsa. Se diseñó una doble Z-plastia con realización de dos colgajos, uno suprapeneano rodeando el escroto ectópico y otro escrotal para modificar el escroto bífido. El colgajo superior se rotó hacia abajo corrigiendo la ectopia y el colgajo inferior corregió la bifidez. No se produjeron complicaciones posoperatorias. El tiempo de seguimiento fue de seis meses con buen aspecto estético final. COMENTARIOS: El escroto ectópico es una malformación congénita infrecuente. Los colgajos de rotación cutáneos con Z-plastias son una opción válida de tratamiento con buenos resultados estéticos a largo plazo.
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Procedimientos de Cirugía Plástica , Anomalías Urogenitales , Humanos , Lactante , Masculino , Pene/anomalías , Pene/cirugía , Procedimientos de Cirugía Plástica/métodos , Escroto , Colgajos Quirúrgicos/cirugía , TestículoRESUMEN
Introducción: La ectopia escrotal constituye una entidad clínicarara, que puede asociar otras anomalías congénitas.Presentamos el caso de un paciente con un pene oculto secundario auna ectopia escrotal, con descripción de la técnica quirúrgica y revisiónde la literatura. Caso clínico: Paciente de un año de vida que presentaba un he-miescroto derecho ectópico con testes en bolsa. Se diseñó una dobleZ-plastia con realización de dos colgajos, uno suprapeneano rodeandoel escroto ectópico y otro escrotal para modificar el escroto bífido.El colgajo superior se rotó hacia abajo corrigiendo la ectopia y elcolgajo inferior corregió la bifidez. No se produjeron complicacionesposoperatorias. El tiempo de seguimiento fue de seis meses con buenaspecto estético final.Comentarios: El escroto ectópico es una malformación congénitainfrecuente. Los colgajos de rotación cutáneos con Z-plastias son una op-ción válida de tratamiento con buenos resultados estéticos a largo plazo.(AU)
Introduction: Ectopic scrotum is a rare clinical entity, potentiallyassociated with other congenital abnormalities. We present the case ofa patient with buried penis secondary to ectopic scrotum. The surgicaltechnique was described, and a literature review was carried out. Clinical case: 1-year-old patient with ectopic right hemiscrotumand the testes within the scrotal sac. A double Z-plasty was performedwith two flaps one above the penis, surrounding the ectopic scrotum,and the other one at the scrotum to modify the bifid scrotum. The up-per flap was rotated downwards, which allowed ectopy to be repaired,and the lower flap was used to repair bifidity. No postoperative com-plications were recorded. Follow-time was 6 months, with good finalcosmetic results. Discussion: Ectopic scrotum is an infrequent congenital malfor-mation. Cutaneous rotation flaps with Z-plasties are a valid treatmentoption, with good long-term cosmetic results.(AU)
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Humanos , Niño , Pene/anomalías , Pene/diagnóstico por imagen , Escroto , Pacientes Internos , Examen Físico , Evaluación de Síntomas , Salud Infantil , Pediatría , Cirugía GeneralRESUMEN
Euphorbia lathyris seeds have been used to treat various medical conditions. We previously reported that ethanolic extract from the defatted seed of Euphorbia lathyris (EE) (variety S3201) possesses a potent in vitro antitumor activity against colon cancer (CRC) cell lines. However, the effects of EE on CRC in vivo models and its possible preventive activity have not been elucidated. The aim of this study is to develop an in vivo study to corroborate its efficacy. For this purpose, two tumor induction models have been developed. In orthotopic xenograft model, it has been shown that EE reduces tumor size without hematological toxicity. The ethanolic extract induced an intense apoptosis in tumors mediated by caspase 3. Using the Azoxymethane/Dextran Sulfate Sodium model, a reduction of dysplastic polyps has been demonstrated, showing its preventive power. Furthermore, EE promoted the presence of an eubiotic microbiotal environment in the mucosa of the colon and induced an increase in antioxidant enzyme activity. This fact was accompanied by a modulation of cytokine expression that could be related to its protective mechanism. Therefore, although further experiments will be necessary to determine its applicability in the treatment of CRC, ES could be a new prevention strategy as well as treatment for this type of tumor, being a powerful candidate for future clinical trials.
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Neoplasias del Colon , Euphorbia , Azoximetano/toxicidad , Neoplasias del Colon/tratamiento farmacológico , Sulfato de Dextran , Etanol , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The most frequently isolated human fungal pathogen is Candida albicans which is responsible for about 50% of all Candida infections. In healthy individuals, this organism resides as a part of the normal microbiota in equilibrium with the host. However, under certain conditions, particularly in immunocompromised patients, this opportunistic pathogen adheres to host cells causing serious systemic infections. Thus, much effort has been dedicated to the study of its physiology with emphasis on factors associated to pathogenicity. A representative analysis deals with the mechanisms of glycoprotein assembly as many cell surface antigens and other macromolecules that modulate the immune system fall within this chemical category. In this regard, studies of the terminal protein glycosylation stage which occurs in Golgi vesicles has led to the identification of nucleotidases that convert glycosyltransferase-generated dinucleotides into the corresponding mononucleotides, thus playing a double function: their activity prevent inhibition of further glycosyl transfer by the accumulation of dinucleotides and the resulting mononucleotides are exchanged by specific membrane transporters for equimolecular amounts of sugar donors from the cytosol. Here, using a simple protocol for protein separation we isolated a bifunctional nucleotidase from C. albicans active on GDP and UDP that was characterized in terms of its molecular mass, response to bivalent ions and other factors, substrate specificity and affinity. Results are discussed in terms of the similarities and differences of this nucleotidase with similar counterparts from other organisms thus contributing to the knowledge of a bifunctional diphosphatase not described before in C. albicans.
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Candida albicans , Candidiasis , Humanos , Pirofosfatasas/metabolismoRESUMEN
PURPOSE: The survival of women with brain metastases (BM) from breast cancer remains very poor, with over 80% dying within a year of their diagnosis. Here, we define the function of IL13Rα2 in outgrowth of breast cancer brain metastases (BCBM) in vitro and in vivo, and postulate IL13Rα2 as a suitable therapeutic target for BM. EXPERIMENTAL DESIGN: We performed IHC staining of IL13Rα2 in BCBM to define its prognostic value. Using inducible shRNAs in TNBC and HER2+ breast-brain metastatic models, we assessed IL13Rα2 function in vitro and in vivo. We performed RNAseq and functional studies to define the molecular mechanisms underlying IL13Rα2 function in BCBM. RESULTS: High IL13Rα2 expression in BCBM predicted worse survival after BM diagnoses. IL13Rα2 was essential for cancer-cell survival, promoting proliferation while repressing invasion. IL13Rα2 KD resulted in FAK downregulation, repression of cell cycle and proliferation mediators, and upregulation of Ephrin B1 signaling. Ephrin-B1 (i) promoted invasion of BC cells in vitro, (ii) marked micrometastasis and invasive fronts in BCBM, and (iii) predicted shorter disease-free survival and BM-free survival (BMFS) in breast primary tumors known to metastasize to the brain. In experimental metastases models, which bypass early tumor invasion, downregulation of IL13Rα2 before or after tumor seeding and brain intravasation decreased BMs, suggesting that IL13Rα2 and the promotion of a proliferative phenotype is critical to BM progression. CONCLUSIONS: Non-genomic phenotypic adaptations at metastatic sites are critical to BM progression and patients' prognosis. This study opens the road to use IL13Rα2 targeting as a therapeutic strategy for BM.
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Neoplasias Encefálicas , Neoplasias de la Mama , Subunidad alfa2 del Receptor de Interleucina-13 , Neoplasias Encefálicas/patología , Neoplasias de la Mama/patología , Proliferación Celular/genética , Femenino , Humanos , Subunidad alfa2 del Receptor de Interleucina-13/genética , Subunidad alfa2 del Receptor de Interleucina-13/uso terapéutico , PronósticoRESUMEN
In this paper, diagnostic tools are utilized to conduct a vulnerability analysis of monuments located in a coastal environment in accordance with a raft of standards drawn up by the International Organization for Standardization (ISO) 31000, in order to identify the main risks for Cultural Heritage in Havana (Cuba) and Cadiz (Spain). Vulnerability analysis is based on a Leopold matrix, which models the relationship between major hazards and pathologies in order to evaluate coastal influence and the risks for the conservation of cultural heritage. The quantitative matrix allows for a cause-effect analysis to be conducted for the main scenarios, related to the state of conservation. These relationships are a key step in risk assessment and treatment strategies. Major hazards have been identified by different public bodies and agencies to provide information about the probability and intensity of these variables in the vulnerability matrix. The combination of vulnerability index assessment, which depends on intrinsic variables and environmental scenarios, and knowledge of the main hazards in Havana and Cadiz, has provided useful tools to conduct risk assessments for cultural heritage conservation in coastal environments, where climate conditions, geomorphology and social issues are the main hazards, while vulnerability is associated with conservation plans. These tools provide information that will enable decision-makers in different coastal environments to prioritize strategies for cultural heritage preservation.
RESUMEN
Based on the stochastic Langevin equation, we derived the total friction experienced by a tracer particle diffusing in thermally equilibrated colloidal magnetic fluids. This transport property leads to new expressions for its long-time diffusion coefficients, which satisfy an Einstein relation with the frictions of its translational and rotational Brownian motion. Further use of the nano-rheology theory allowed us to derive also the viscoelastic modulus of the colloid from such a property. The temporal relaxation of the viscoelasticity and transport coefficient turns out to be governed by the intermediate scattering function of the colloid. We derived an explicit formula for this evolution function within a hydrodynamic theory to include rotational degrees of freedom of the particles. In the limit of short frequencies, the viscous moduli render a new expression for the static viscosity. We found that its comparison with known experiments, at low and high concentration of ferroparticles in magnetite ferrofluids, is fair. However, comparing the predicted viscoelastic moduli with computer simulations as a function of frequency yields poor agreement.
RESUMEN
BACKGROUND AND AIMS: In France, there are approximately 2,400 new cases of neuroendocrine tumors (NETs) annually. Peptide receptor radionuclide therapy with 177Lu-Dotatate plus long-acting repeatable [LAR] octreotide 30 mg has been shown to significantly improve progression-free survival and overall survival relative to high-dose octreotide LAR 60 mg in patients with unresectable or metastatic progressive midgut NETs. A long-term cost-effectiveness analysis was performed to assess whether 177Lu-Dotatate is a cost-effective option versus octreotide 60 mg for patients with unresectable/metastatic progressive midgut NETs from the perspective of French healthcare payer. METHODS: The analysis was performed using a three-state partitioned survival model. In the base case analysis 177Lu-Dotatate plus octreotide LAR 30 mg was compared with high-dose octreotide LAR 60 mg in patients with midgut NETs. Survival data were obtained from the phase III NETTER-1 trial in patients with metastatic midgut NETs. Future costs and clinical outcomes were discounted at 4% per annum. One-way deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, for patients with midgut NETs, 177Lu-Dotatate treatment improved quality-adjusted life expectancy by 1.21 quality-adjusted life years (QALYs) relative to octreotide LAR 60 mg and the lifetime treatment costs were EUR 50,784 higher with 177Lu-Dotatate resulting in an incremental cost-effectiveness ratio (ICER) of EUR 42,106 per QALY gained versus octreotide LAR 60 mg. When compared with everolimus, 177Lu-Dotatate was associated with an ICER of EUR 59,769 per QALY gained. Sensitivity analyses showed that the results were sensitive to methods used to extrapolate survival data. CONCLUSIONS: For patients with advanced progressive midgut NETs 177Lu-Dotatate is likely to be considered a cost-effective option versus octreotide 60 mg from the perspective of the French healthcare payer.