RESUMO
Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in the Bragg peak area and biological washout of PET emitters. The use of contrast agents including 18O, 68Zn or 63Cu, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of 18O-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (18F) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough 18O into a living organism to produce a detectable signal from 18F after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of 18F (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which confirms that low-energy protons can indeed produce a detectable PET signal if a suitable contrast agent is employed. Moreover, dynamic PET studies in two of the eggs evidenced a minimal effect of biological washout, with 68% retained specific 18F activity at 8 h after irradiation. Furthermore, ex-vivo analysis of 4 irradiated tumours showed that up to 3% of oxygen atoms in the targets were replaced by 18O from infused 18-W, and evidenced an entrapment of 59% for specific activity of 18F after washing, supporting our hypothesis that F- ions remain trapped within the cells. An infusion of 18-W can incorporate 18O in animal tissues by replacing regular water inside cells, producing a PET signal when irradiated with low-energy protons that could be used for range verification in protontherapy. 18F produced inside cells remains entrapped and suffers from minimal biological washout, allowing for a sharper localization with longer PET acquisitions. Further studies must evaluate the feasibility of this technique in dosimetric conditions closer to clinical practice, in order to define potential protocols for its use in patients.
Assuntos
Neoplasias da Mama , Terapia com Prótons , Animais , Embrião de Galinha , Galinhas , Meios de Contraste , Feminino , Radioisótopos de Flúor , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prótons , ÁguaRESUMO
Passive dosimetry with radiochromic films is widely used in proton radiotherapy, both in clinical and scientific environments, thanks to its simplicity, high spatial resolution and dose-rate independence. However, film under-response for low-energy protons, the so-called linear-energy transfer (LET) quenching, must be accounted and corrected for. We perform a meta-analysis on existing film under-response data with EBT, EBT2 and EBT3 GAFchromic™ films and provide a common framework to integrate it, based on the calculation of dose-averaged LET in the active layer of the films. We also report on direct measurements with the 10 MeV proton beam at the Center for Microanalysis of Materials (CMAM) for EBT2, EBT3 and unlaminated EBT3 films, focusing on the 20-80 keVµm-1LET range, where previous data was scarce. Measured film relative efficiency (RE) values are in agreement with previously reported data from the literature. A model on film RE constructed with combined literature and own experimental values in the 5-80 keVµm-1LET range is presented, supporting the hypothesis of a linear decrease of RE with LET, with no remarkable differences between the three types of films analyzed.
Assuntos
Dosimetria Fotográfica , Prótons , Calibragem , RadiometriaRESUMO
BACKGROUND: Most patients with cerebral palsy (CP) do not respond to physical therapy due to deterioration in their nutritional status, secondary to gastrointestinal disorders and the catabolic state of the disease itself. However, basic treatments only contemplate the energy requirements and do not consider supplementation with glutamine, zinc, selenium, colecalciferol, spirulina, omega 3 or even vegetal proteins. OBJECTIVE: In this study, we determined the effect of using a nutritional support system (NSS): diet and supplements, on the gross motor function in children with CP with spastic diparesic and Gross Motor Function Classification System III (GMFCS III). METHODS: An exploratory study was performed. Thirty patients (from 4 to 12 years old) were randomly assigned to: (1) dietary surveillance (FG), (2) deworming and WHO diet (CG), or (3) deworming and the NSS (IG). Gross motor function was evaluated using the gross motor function measure (GMFM) scale. RESULTS: The IG-treated group presented a significant improvement in standing and walking parameters analyzed in the GMFM compared with FG and CG groups. Fifty percent of the IG-treated patients managed to walk, while in the other groups, no patients were able to walk. CONCLUSIONS: The NSS used in the present work improves gross motor function and promotes walking in patients with CP.
RESUMO
Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16INK4a -positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16INK4a expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.
Assuntos
Senescência Celular/efeitos da radiação , Radiação Ionizante , Baço/metabolismo , Baço/efeitos da radiação , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Animais , Antivirais/uso terapêutico , Infecções por Arenaviridae/tratamento farmacológico , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/virologia , Proliferação de Células/efeitos da radiação , Células Cultivadas , Senescência Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Ganciclovir/uso terapêutico , Vírus da Coriomeningite Linfocítica/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Fenótipo , Rejuvenescimento/fisiologia , Baço/virologiaRESUMO
Introducción: en la formación de pregrado debe concederse la debida importancia a la enseñanza de la reumatología dado su carácter multidisciplinar, que demanda un futuro profesional de la salud capaz de valorar y reconocer aún desde aulas y laboratorios, las implicaciones sociales y de salud entre enfermedades reumáticas y oculares ya que el diagnóstico correcto de estas, puede ayudar a destacar el rol del proceso sistémico y viceversa. Objetivo: evaluar el nivel de conocimientos de estudiantes de medicina sobre las afecciones oftalmológicas más frecuentes en la práctica de la reumatología. Métodos: la investigación se realizó en la facultad de Medicina perteneciente a la Universidad Regional Autónoma de los Andes en el período comprendido de marzo a mayo de 2017. Se trata de un estudio descriptivo, transversal y analítico. El universo estuvo constituido por 166 estudiantes de VI y VII semestres y la muestra de estudio la constituyeron 75 estudiantes de cada semestre seleccionados al azar. Resultados: la presencia mayoritaria de mujeres caracteriza a la muestra objeto de estudio (53.3 por ciento, contra 46,7 por ciento de hombres). Las edades máximas y mínimas fueron 21 y 26 años respectivamente, con edad promedio superior en el VII semestre. Se aplicó una encuesta validada previamente que permitió evaluar el conocimiento relacionado con las manifestaciones oftalmológicas más frecuentes. Conclusiones: el nivel de conocimiento sobre las manifestaciones oftalmológicas en la práctica de la reumatología no es bueno, por lo que se sugiere redimensionar el proceso docente, privilegiando la formación práctica que debe caracterizar la enseñanza de pregrado al profundizar en el manejo de estas entidades(AU)
Introduction: In the undergraduate training must be given due importance to the teaching of rheumatology because of its multidisciplinary character, which demands a future health professional able to assess and recognize even from classrooms and laboratories, the social and health implications between rheumatic and ocular diseases because the correct diagnosis of these can help highlighting the role of the systemic process and vice versa. Objective: To assess the level of medical students´ knowledge about the most common ophthalmological conditions in the practice of rheumatology. Methods: The research was carried out in the Faculty of Medicine belonging to the Universidad Regional Autónoma de los Andes from March to May, 2017. It is a descriptive, transversal and analytical study. The universe was constituted by 166 students of sixth and seventh semesters and the sample of study was constituted by 75 students of each semester selected at random. Development: The majority presence of women characterizes the sample object of study (53.3 percent against 46.7 percent of men). The maximum and minimum wages were 21 and 26 years old respectively, with a higher average age in the seventh semester. A previously validated survey was applied that allowed evaluating the knowledge related to the most frequent ophthalmologic manifestations. Conclusions: The level of knowledge on the ophthalmologic manifestations in the practice of rheumatology is not good, so it is suggested to resize the teaching process, favoring the practical training that must characterize the teaching of undergraduate to deepen the management of these entities(AU)
Assuntos
Humanos , Adulto Jovem , Reumatologia , Faculdades de Medicina , Estudantes de Medicina , Doenças Reumáticas , Conhecimento , Epidemiologia Descritiva , Estudos Transversais , Educação Médica/normas , Oftalmopatias/prevenção & controleRESUMO
Virtual environment interaction has been studied from different theoretical-methodological approaches. The purpose of this paper is to describe the characteristics of written texts in a blended learning course, and to analyze six theoretical systems that contrast them with data. The collected data come from all the texts written in Moodle by the teacher in a year-long course. The variables were set up from six approaches (coding systems): (a)- Communities of inquiry; (b)- Teaching assistance dimensions; (c)- Macro and micro-scripting; (d)- Twelve ways of teaching; (e)- Rethinking the class; and (f)- Observation record. Reliability and multivariable analyses were carried out. Results showed different consistency of approaches. The analyzed texts revealed how interaction took place and showed pedagogical issues underlying the didactic proposals. Associations among categories produced three typical groups of texts related with the different variables from theoretical-methodological coding systems used: Cluster 1 gathered general instructions; Cluster 2 illustrated the virtual environment usage as repository; and Cluster 3 represented tutorial interactivity. Future studies should continue to explore these approaches, contrasting them with new data -and vice versa- to get a better understanding of socio-cognitive interaction among students and teachers in blended learning
La interacción del entorno virtual ha sido estudiada desde diferentes enfoques teórico-metodológicos. El propósito de este artículo es describir las características de los textos escritos en un curso de aprendizaje combinado y analizar seis sistemas teóricos que los contrastan con los datos. Los datos recopilados son de todos los textos escritos en Moodle por el profesor en un curso de un año. Las variables se configuraron a partir de seis enfoques (sistemas de codificación): (a) - Comunidades de investigación; (b) - Dimensiones de la asistencia docente; (c) - Macro y micro-scripting; (d) - Doce formas de enseñar; (e) - Repensando la clase; y (f) - Registro de observación. Se realizaron análisis de fiabilidad y multivariables. Los resultados mostraron diferente consistencia de los enfoques. Los textos analizados revelaron cómo tuvo lugar la interacción y mostraron problemas pedagógicos subyacentes a las propuestas didácticas. Las asociaciones entre categorías produjeron tres grupos típicos de textos relacionados con las diferentes variables de los sistemas de codificación teórico-metodológicos utilizados: el grupo 1 reunió instrucciones generales; El cluster 2 ilustra el uso del entorno virtual como repositorio; y Cluster 3 representó la interactividad tutorial. Los estudios futuros deben continuar explorando estos enfoques, contrastándolos con datos nuevos, y viceversa, para obtener una mejor comprensión de la interacción sociocognitiva entre estudiantes y maestros en el aprendizaje combinado
Assuntos
Humanos , Ensino , Compreensão , Aprendizagem , Pesquisa , Estudantes , Cursos , Docentes , Codificação Clínica , Professores EscolaresRESUMO
La finalidad de este estudio fue verificar los estándares de calidad que se dan dentro de la Clínica Odontológica CES Sabaneta, partiendo del sistema de habilitación preescrito en el decreto 2309 del 2002 y las resoluciones 1439 y 1474 del mismo año. Para realizar esta evaluación se empleó un formulario donde se especificó cada uno de los estándares, los cuales fueron: condiciones básicas para una institución prestadora de servicios de salud, consulta externa, métodos de esterilización y técnicas de imagenología. Se realizaron encuestas a 410 usuarios, (335 usuarios externos) y (75 usuarios internos), con el propósito de realizar un análisis del grado de satisfacción de los clientes. El instrumento utilizado para evaluar a los usuarios, tanto internos como externos fue diferente para ambos, valorando aspectos pertinentes para cada uno. Los usuarios externos evaluaron la ubicación geográfica, amabilidad del personal de la clínica, infraestructura y duración de los tratamientos. En cuantos a los usuarios internos, esto lo hicieron con respecto a su relación con todo el personal que labora en la clínica, tarifas laborales, flujo de pacientes, infraestructura y satisfacción persona en cuanto a su función. El grado de satisfacción obtenido por parte de los usuarios internos y externos es alto, como también lo fueron, las condiciones requeridas por la Clínica Odontológica CES Sabaneta para trabajar como institución prestadora de servicios de salud...