RESUMO
This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics.
Assuntos
Liberação Controlada de Fármacos , Felodipino , Derivados da Hipromelose , Impressão Tridimensional , Solubilidade , Comprimidos , Felodipino/química , Felodipino/administração & dosagem , Derivados da Hipromelose/química , Composição de Medicamentos/métodos , Simulação de Dinâmica Molecular , Portadores de Fármacos/química , Preparações de Ação Retardada/química , Química Farmacêutica/métodos , Tecnologia de Extrusão por Fusão a Quente/métodos , Tecnologia Farmacêutica/métodosRESUMO
Gastrointestinal (GI) environment is influenced by several factors (gender, genetics, sex, disease state, food) leading to oral drug absorption variability or to low bioavailability. In this scenario, gastroretentive drug delivery systems (GRDDS) have been developed in order to solve absorption problems, to lead to a more effective local therapy or to allow sustained drug release during a longer time period than the typical oral sustained release dosage forms. Among all GRDDS, floating systems seem to provide a promising and practical approach for achieving a long intra-gastric residence time and sustained release profile. In the last years, a novel technique is being used to manufacture this kind of systems: three-dimensional (3D) printing technology. This technique provides a versatile and easy process to manufacture personalized drug delivery systems. This work presents a systematic review of the main 3D printing based designs proposed up to date to manufacture floating systems. We have also summarized the most important parameters involved in buoyancy and sustained release of the systems, in order to facilitate the scale up of this technology to industrial level. Finally, a section discussing about the influence of materials in drug release, their biocompatibility and safety considerations have been included.
RESUMO
Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. The aim of this work was to prepare 3DP gastroretentive floating tablets designed to provide a controlled release of the API. Metformin was used as a non-molten model drug and hydroxypropylmethyl cellulose with null or negligible toxicity was the main carrier. High drug loads were assayed. Another objective was to maintain the release kinetics as robust as possible when varying drug doses from one patient to another. Floating tablets using 10-50% w/w drug-loaded filaments were obtained by Fused Deposition Modelling (FDM) 3DP. The sealing layers of our design allowed successful buoyancy of the systems and sustained drug release for more than 8 h. Moreover, the effect of different variables on the drug release behaviour was studied. It should be highlighted that the robustness of the release kinetics was affected by varying the internal mesh size, and therefore the drug load. This could represent a step forward in the personalization of the treatments, a key advantage of 3DP technology in the pharmaceutical field.
RESUMO
BACKGROUND: Several laboratory techniques for anti double-stranded (ds) DNA detection in systemic lupus erythematosus (SLE) are available, with variable diagnostic performance. We aimed to evaluate anti-dsDNA's diagnostic performance by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (EIA). METHODS: We conducted a single-center retrospective (2015 to 2020) study. Patients with anti-dsDNA tests by IIF and EIA were included. We evaluated the indications, applications, concordance, positive predictive value (PPV) of anti-dsDNA to confirm SLE diagnosis or flares, and associations of disease manifestations with positivity with each technique. RESULTS: A total of 1368 reports of anti-dsDNA tests by IIF and EIA and the corresponding medical records of the patients were analyzed. The main indication for anti-dsDNA testing was to help in the diagnosis of SLE in 890 (65%) of the samples, and the main application after obtaining the results was SLE exclusion in 782 (57.2%) cases. The combination with the highest frequency was the negativity result by both techniques in 801 (58.5%) cases (Cohen kappa 0.57). Both methods were positive in 300 patients with SLE (Cohen kappa 0.42). The PPVs of anti-dsDNA tests to confirm diagnosis/flare was 79.64% (95% CI, 75.35-83.35) by EIA, 78.75% (95% CI, 74.27-82.62) by IIF, and 82% (95% CI, 77.26-85.93) when both were positive. CONCLUSIONS: Anti-dsDNA detection by IIF and EIA are complementary and may indicate different clinical patterns in patients with SLE. The detection of anti-dsDNA antibodies by both techniques has a higher PPV than either separately for confirming SLE diagnosis or flares. These results highlight the need for evaluating both methods in clinical practice.
Assuntos
Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico , Humanos , Ensaio de Imunoadsorção Enzimática/normas , Técnica Indireta de Fluorescência para Anticorpo/normas , Lúpus Eritematoso Sistêmico/diagnóstico , Estudos Retrospectivos , Anticorpos Antinucleares/análise , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de RegressãoRESUMO
This study presents the design, effect and utility of using audiovisual material containing real images of dissected human cadavers as an innovative educational strategy (IES) in the teaching of Human Anatomy. The goal is to familiarize students with the practice of dissection and to transmit the importance and necessity of this discipline, while modulating their anxiety. The study included 303 first-year Human Anatomy students, randomly assigned to two groups (Traditional and Educational Innovation). Their state of anxiety was measured using the State-Trait-Anxiety Inventory. Repeated measures ANOVA with between-subject factors was applied. The between-subject factor was Educational Innovation (EI). Two levels were established for this factor. The within-subject factor was Time, four levels being considered here. The results show that the effects of the Educational Innovation factor, Time factor and EI × Time interaction were statistically significant. These results provide an additional element of efficacy to the use of videos as an IES. That is, the use of video material as an introduction into an anxiety-provoking situation which resembles real-life viewing and interaction with human cadavers for the first time significantly diminishes the anticipatory reaction of dread against which novel students have not had the opportunity to develop any cognitive strategy of emotional control.
Assuntos
Anatomia/educação , Ansiedade/prevenção & controle , Recursos Audiovisuais , Educação de Graduação em Medicina , Estudantes de Medicina/psicologia , Adolescente , Ansiedade/classificação , Dissecação/educação , Educação Médica , Feminino , Humanos , Masculino , Espanha , Adulto JovemRESUMO
Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30-40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component.
RESUMO
The use of 3D printing technology in the manufacturing of drug delivery systems has expanded and benefit of a customized care. The ability to create tailor-made structures filled with drugs/delivery systems with suitable drug dosage is especially appealing in the field of nanomedicine. In this work, chitosan-based polymeric micelles loaded with camptothecin (CPT) were incorporated into 3D printing systems (printfills) sealed with an enteric layer, aiming to protect the nanosystems from the harsh environment of the gastrointestinal tract (GIT). Polymeric micelles and printfills were fully characterized and, a simulated digestion of the 3D systems upon an oral administration was performed. The printfills maintained intact at the simulated gastric pH of the stomach and, only released the micelles at the colonic pH. From there, the dissolution media was used to recreate the intestinal absorption and, chitosan micelles showed a significant increase of the CPT permeability compared to the free drug, reaching an apparent permeability coefficient (Papp) of around 9×10-6 cm/s in a 3D intestinal cell-based model. The combination of 3D printing with nanotechnology appears to have great potential for the colon-specific release of polymeric micelles, thereby increasing intestinal absorption while protecting the system/drug from degradation throughout the GIT.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Quitosana/química , Sistemas de Liberação de Medicamentos , Administração Oral , Antineoplásicos Fitogênicos/farmacocinética , Células CACO-2 , Camptotecina/farmacocinética , Colo/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal , Micelas , Polímeros/química , Impressão TridimensionalRESUMO
A biodegradable copolyester, poly(butylene succinate-co-ε-caprolactone) (PBS_CL), was used for first time as an excipient for pharmaceutical dosage forms using direct compression and hot processing techniques (ultrasound-assisted compression (USAC) and hot melt extrusion (HME)). Robust binary systems were achieved with hot processing techniques, allowing a controlled release of the drug. With only 12% v/v of PBS_CL, controlled release forms were obtained using USAC whereas in HME over 34% v/v of excipient is necessary. Amounts over 23% v/v allowed a long-extended release for more than 72 h following diffusional kinetic. Thanks to the high melting point of theophylline and the physicochemical properties of PBS_CL selected and synthesized, the structure of the excipient inside the USAC tablets and HME filaments corresponds to a continuum medium. A percolation threshold around 23% v/v was estimated, which agrees with a continuum percolation model. The polymer shows a high excipient efficiency value using HME and USAC. A nanostructured matrix with wall thicknesses lower than 0.1 µm was obtained. This leads to a very effective coating of the drug particles by the excipient, providing a slow and reproducible release. The present study therefore supports the use of PBS_CL, for the preparation of controlled release dosage forms using hot processing techniques.
RESUMO
In the present study, the efficacy of a formal mentoring program applied to fourth and fifth year students of the Psychology Faculty of the Complutense University is assessed. In this program, fifth-year students took on the role of mentors and fourth-year students, the role of mentees. To assess the efficacy, the group of mentors was compared with a group of non-mentors and the group of mentees with a group of non-mentees, before and after the program, taking into account the variables related to career development function (knowledge acquired of the academic setting and satisfaction with the career of Psychology) and the psychosocial function (self-concept, self-esteem, self-efficacy, and involvement). The results show a statistically significant increase in the knowledge acquired about the academic setting as a consequence of the program, both in the group of mentors and in the group of mentees. Moreover, the mentors achieved a better average grade in the subjects of the specialty of Work Psychology. There were no statistically significant differences between the experimental group and the control group in satisfaction with the career of Psychology, or in self-concept, self-esteem, or self-efficacy.
Assuntos
Escolha da Profissão , Mentores/psicologia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Grupo Associado , Psicologia/educação , Logro , Feminino , Humanos , Satisfação no Emprego , Masculino , Autoimagem , Identificação Social , Adulto JovemRESUMO
The skin is the largest organ in the human body. Among other components, it contains epidermal cells, which are modified epithelial cells that rest on a basal membrane that separates them from the dermis. When the epidermis presents variations in its structural composition and the distribution of its elements, the result is the loss of large amounts of water, which perpetuates these variations and leads to permanent dehydration. Emollients are the first line of treatment for pathologies that affect the hydration of the skin, such as atopic dermatitis, which is one of the most important ones. This document entails the description of the epidermal barrier with its main components and functions, the characteristics of an altered skin barrier, and the mechanisms for its repair. Subsequently, this paper includes the definition of emollient, hydration mechanisms for the recovery of the barrier, types of emollients, the situations that must be taken into account when the use of emollients is prescribed, evidence with or without connection with their advantages, and the key points at the time of its formulation.
La piel es el órgano más extenso del cuerpo humano; entre otros componentes comprende las células epidérmicas, la cuales son células epiteliales modificadas que descansan sobre una membrana basal separadas de la dermis. Al presentar modificaciones en su composición estructural y la distribución de sus elementos, la epidermis pierde grandes cantidades de agua, lo que perpetúa estas variaciones y llevan a deshidratación permanente. Los emolientes constituyen la primera línea de manejo para las patologías que afectan la hidratación de la piel, entre ellas una de las más importantes es la dermatitis atópica. En este documento se describe la barrera epidérmica con sus principales componentes y funciones, las características de una barrera cutánea alterada y los mecanismos para su reparación. Posteriormente se continúa con la definición de emoliente, mecanismos de hidratación para la recuperación de la barrera, tipos de emolientes, situaciones que deben considerarse al indicar su uso, la evidencia en relación con sus ventajas o no y los puntos clave al realizar su formulación.
Assuntos
Emolientes/uso terapêutico , Dermatopatias/tratamento farmacológico , Emolientes/farmacologia , Humanos , Pele/efeitos dos fármacosRESUMO
OBJECTIVE: Bariatric surgery is a widely used procedure for the treatment of obesity. Our aim is to describe the main immunological changes in patients who undergo bariatric surgery. METHODS: A prospective study was conducted within a cohort of patients undergoing bariatric surgery and without previous evidence of systemic or organ-specific autoimmune diseases in whom 3 blood samples were collected - one day before surgery (Time 0), and 5 (Time 1) and 10 months (Time 2) after surgery. RESULTS: Thirty four obese patients underwent surgery (Time 0):30(88.24%) were women, mean age 38.3 years. When comparing Time 0 and Time 2, there were statistically significant changes in CD4+T cell count, with an increase from 1074/mL(IQR:860-1316) to 1217.5/mL(IQR:838-1510),pâ¯=â¯0.0002. The CD4/CD8 ratio increased from 2.2(IQR: 1.7-2.7) to 2.4(1.8-2.8), pâ¯=â¯0.0001. As for humoral variables, the C3 fraction of complement decreased from 164⯱â¯40.6â¯mg/dL to 112.4⯱â¯31.4â¯mg/dL(pâ¯<â¯0.001) and C4 decreased from 29.3⯱â¯10.1â¯mg/dL to 22.5⯱â¯7.1(pâ¯=â¯0.0009) at Time 2. Four patients with negative ANAs at baseline, showed positive ANAs at Time 2.One patient developed anti-citrullinated peptide antibodies >200 IU/mL at Time 2. CONCLUSIONS: Patients undergoing bariatric surgery show immunological changes which might eventually lead to develop an autoimmune disease.
RESUMO
ABSTRACT Introduction: Lupus nephritis (LN) is one of the most prevalent and severe complications of systemic lupus erythematosus (SLE), requiring reliable urine and serum biomarkers to evaluate it. Anti-nucleosome and anti-C1q antibodies are associated with LN in several geographic regions. Also, southwest Colombia has a heterogeneous ethnicity, which motivated the evaluation of the frequency and relationship of such markers with LN in this region. Methods: A cross-sectional study was conducted in a health centre in south-west Colombia in 84 patients diagnosed with SLE (57 without LN; 27 with LN) between 2016 and 2018. Demographic and clinical and laboratory features, including anti-dsDNA, complement, and anti-C1q and anti-nucleosome antibodies were compared in these patients. ELISA immunoassays were performed to measure the antibodies of interest in blood samples. Statistical analysis was carried out using STATA14 software (StataCorp, College Station, Texas, USA). Quantitative variables were summarised as means or medians and compared with Mann-Whitney or Two-sample t test. Categorical variables were shown as proportions, and compared with Chi-squared or Fisher's exact test. Correlation analysis between quantitative variables was calculated using Spearman's correlation. Results: Of all 84 patients, 27 patients had LN, of which 16 (59.2%) had a positive test for anti-nucleosome antibodies and 10 (37%) for anti-C1q antibodies. An association was found between anti-C1q and proliferative forms of LN and newly diagnosed LN. A correlation was found between anti-nucleosome and anti-C1q antibodies, and anti-dsDNA and low serum complement concentrations. Conclusion: Although both markers were found in variable percentages in SLE patients and seem not to be specific markers of LN in our population, anti-C1q was associated with proliferative forms of LN and de novo LN.
RESUMEN Introducción: La nefritis lúpica (NL), una de las complicaciones más frecuentes y graves del lupus eritematoso sistémico (LES), requiere biomarcadores confiables de orina y suero para su evaluación. Los anticuerpos anti-nucleosoma y anti-C1q se asocian con la NL en varias regiones geográficas. En el suroccidente colombiano se asienta una etnia heterogénea, lo que motivó la evaluación de la frecuencia y la relación de dichos marcadores con NL en dicha región. Métodos: Realizamos un estudio transversal en un centro de salud en el suroccidente de Colombia, con 84 pacientes diagnosticados con LES (57 sin NL; 27 con NL) entre los anos 2016 y 2018. Se compararon las características demográficas, clínicas y de laboratorio, incluidos los anticuerpos anti-dsDNA, complemento, anti-C1q y anti-nucleosomas entre estos pacientes. Se realizaron inmunoensayos ELISA para medir los anticuerpos de interés en muestras de sangre. El análisis estadístico se llevó a cabo con el software Stata v.14 (Stata-Corp, College Station, Texas, EE. UU.). Las variables cuantitativas se resumieron como medias o medianas y se compararon con la prueba t de Mann-Whitney o Two-sample t test; las variables categóricas se mostraron como proporciones y se compararon con Chi-cuadrado o con la prueba exacta de Fisher. Para el análisis de correlaciones entre variables cuantitativas se calculó el coeficiente de correlación de Spearman. Resultados: Entre los 84 pacientes, 27 presentaban LN, de los cuales 16 (59,2%) tuvieron una prueba positiva para anticuerpos anti-nucleosoma y 10 (37%) para anticuerpos anti-C1q. Se encontró una asociación entre anti-C1q y formas proliferativas de NL, así como formas recientemente diagnosticadas de NL. Hubo una correlación entre los anticuerpos anti-nucleosoma y anti-C1q y el anti-dsDNA y las bajas concentraciones de complemento sérico. Conclusión: Aunque los 2 marcadores se encontraron en porcentajes variables de pacientes con LES y no parecen ser marcadores específicos de NL en nuestra población, la presencia de anti-C1q se asoció con formas proliferativas de NL y NL de novo.
Assuntos
Humanos , Nefrite Lúpica , Lúpus Eritematoso Sistêmico , Anticorpos , Pesos e Medidas , Imunoensaio , Etnicidade , LaboratóriosRESUMO
INTRODUCTION: In vitro models with high predictive ability have been revealed as strong tools for pharmaceutical industry. However, the variability in permeability estimations complicates the comparison and combination of data from different laboratories and it makes necessary the careful validation of the model and the continuous suitability demonstration. The adequate standardization of pre-experimental, experimental and post-experimental factors might help to reduce the inter- and intra-laboratory variability in permeability values. METHODS: The objective of this paper is the evaluation of the effect of passage number, experimental protocol, time after seeding and calculation method on the permeability values and their variability in transport experiments in Caco-2, MDCK and MDCK-MDR1 cells. Metoprolol, Lucifer yellow and Rhodamine-123 were used to check the performance of the cell lines. Protocols used differ mainly in the differentiation time and the filter support coating with collagen. Data was analyzed with sink and non-sink approaches. The final purpose was to explore pre-experimental, experimental and post-experimental conditions in order to select the best experimental scenarios for permeability assays. RESULTS: Results indicated that for passive diffusion studies, coating helps cell differentiation in a more stable manner in all cell lines compared to protocol without coating which showed permeability changes with passages and more variable values. In both protocols the paracellular route became more restricted with higher passage numbers. Functionality of P-gp assessed with Rhodamine permeability did not change with passage number in Caco-2 cells with any of the protocols but increased in both protocols in MDCK and MDCK-MDR1 cells. Protocol without coating showed the less variable results in these cell lines. Rhodamine permeabilities increased with higher maturation times due to a higher expression of the transporter. Nevertheless for compounds absorbed by passive diffusion there was not a clear trend neither in permeability values nor in variability. DISCUSSION: As a conclusion, we have confirmed the influence of maturation conditions and passage number in permeability values and in their variability. Based on our results protocol with coating would be more adequate for studies of compounds absorbed by passive diffusion but the protocol without coating gave us better results for studies about P-gp interactions.
Assuntos
Técnicas de Cultura de Células , Permeabilidade da Membrana Celular , Animais , Transporte Biológico , Células CACO-2 , Células Cultivadas , Cães , Humanos , Células Madin Darby de Rim CaninoRESUMO
Introducción: La diferenciación entre actividad lúpica de infecciones en pacientes con lupus eritematoso sistémico (LES) es difícil debido a una presentación clínica similar. El objetivo es evaluar la utilidad de una serie de biomarcadores para diferenciar infecciones de actividad en pacientes con LES admitidos con respuesta inflamatoria sistémica (SIRS). Métodos: Pacientes con LES y SIRS que consultaron al servicio de urgencias fueron seleccionados. Se realizaron mediciones de diferentes marcadores como procalcitonina, expresión de CD64 de neutrófilos y presepsina al ingreso y fueron comparados con la presencia o no de infección, la cual se consideró presente con cultivos positivos y/o evidencia microbiológica por PCR. Se calculó la sensibilidad y especificidad de cada biomarcador y puntos de corte usando curvas ROC.
Assuntos
Lúpus Eritematoso Sistêmico , Calcitonina , Receptores de IgGRESUMO
In the present study, the efficacy of a formal mentoring program applied to fourth and fifth year students of the Psychology Faculty of the Complutense University is assessed. In this program, fifth-year students took on the role of mentors and fourth-year students, the role of mentees. To assess the efficacy, the group of mentors was compared with a group of nonmentors and the group of mentees with a group of non-mentees, before and after the program, taking into account the variables related to career development function (knowledge acquired of the academic setting and satisfaction with the career of Psychology) and the psychosocial function (self-concept, self-esteem, self-efficacy, and involvement). The results show a statistically significant increase in the knowledge acquired about the academic setting as a consequence of the program, both in the group of mentors and in the group of mentees. Moreover, the mentors achieved a better average grade in the subjects of the specialty of Work Psychology. There were no statistically significant differences between the experimental group and the control group in satisfaction with the career of Psychology, or in self-concept, self-esteem, or self-efficacy (AU)
En el presente estudio se evalúa la eficacia de un programa de mentoring formal implantado en la Facultad de Psicología de la Universidad Complutense en alumnos de segundo ciclo. En dicho programa los alumnos de quinto curso asumían el rol de mentores y los de cuarto curso el rol de telémacos. Para evaluar la eficacia se contrasta el grupo de mentores con el grupo de no mentores y el grupo de telémacos con el grupo de no telémacos, antes y después del programa, atendiendo a variables relacionadas con la función de desarrollo de carrera (conocimientos adquiridos sobre el entorno académico, y satisfacción con la carrera de Psicología) y con la función psicosocial (autoconcepto, autoestima, autoeficacia e implicación). Los resultados encontrados muestran un incremento estadísticamente significativo en los conocimientos adquiridos respecto al entorno académico como consecuencia del programa, tanto para el grupo de mentores como para el grupo de telémacos. Además, los mentores consiguen un mejor promedio en las calificaciones de las asignaturas de la especialidad de Psicología del Trabajo. No aparecen diferencias estadísticamente significativas entre el grupo experimental y el grupo control ni en la satisfacción con la carrera de Psicología, ni en el autoconcepto, la autoestima y la autoeficacia (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Eficácia/métodos , Eficácia/normas , Avaliação de Eficácia-Efetividade de Intervenções , Estudantes/psicologia , Estudantes de Ciências da Saúde/psicologia , Mentores/psicologia , Satisfação Pessoal , Autoimagem , Autoeficácia , Trabalho/psicologia , Mentores/classificação , Mentores/educação , Mentores/estatística & dados numéricos , Apoio Social , Impacto PsicossocialRESUMO
No disponible