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Melanin is an insoluble, amorphous polymer that forms planar sheets that aggregate naturally to create colloidal particles with several biological functions. Based on this, here, a preformed recombinant melanin (PRM) was utilized as the polymeric raw material to generate recombinant melanin nanoparticles (RMNPs). These nanoparticles were prepared using bottom-up (nanocrystallization-NC, and double emulsion-solvent evaporation-DE) and top-down (high-pressure homogenization-HP) manufacturing approaches. The particle size, Z-potential, identity, stability, morphology, and solid-state properties were evaluated. RMNP biocompatibility was determined in human embryogenic kidney (HEK293) and human epidermal keratinocyte (HEKn) cell lines. RMNPs prepared by NC reached a particle size of 245.9 ± 31.5 nm and a Z-potential of -20.2 ± 1.56 mV; 253.1 ± 30.6 nm and -39.2 ± 0.56 mV compared to that obtained by DE, as well as RMNPs of 302.2 ± 69.9 nm and -38.6 ± 2.25 mV using HP. Spherical and solid nanostructures in the bottom-up approaches were observed; however, they were an irregular shape with a wide size distribution when the HP method was applied. Infrared (IR) spectra showed no changes in the chemical structure of the melanin after the manufacturing process but did exhibit an amorphous crystal rearrangement according to calorimetric and PXRD analysis. All RMNPs presented long stability in an aqueous suspension and resistance to being sterilized by wet steam and ultraviolet (UV) radiation. Finally, cytotoxicity assays showed that RMNPs are safe up to 100 µg/mL. These findings open new possibilities for obtaining melanin nanoparticles with potential applications in drug delivery, tissue engineering, diagnosis, and sun protection, among others.
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This article describes a curriculum developed as part of the American Psychological Association President Jessica Henderson Daniel's, 2018 Presidential Initiative-The Citizen Psychologist. The curriculum is designed to prepare the next generation of Citizen Psychologists to provide the broadest sense of service as leaders in their communities and in public service psychology. The curriculum prepares the learner to bring psychological knowledge, science, and expertise to bear on existing challenges to improve community well-being locally, nationally, and globally. This includes addressing the services needs of various vulnerable populations such as veterans, prisoners, the seriously mentally ill, those with substance abuse problems, children, and older adults. Competency-based curricula are presented in a series of modules, each dedicated to a level of education and training from high school through lifelong learning. Each module presents learning outcomes, activities, and resources designed to develop level-specific competencies. Steps for implementation and recommendations at the local and national level are provided. Implications of incorporating the Citizen Psychologist curriculum in education and training programs are discussed including encouraging students to explore volunteer and career opportunities in public service psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Subject(s)
Curriculum , Societies, Scientific , Aged , Child , HumansABSTRACT
BACKGROUND: Gene expression profiles have demonstrated that miR-21 expression is altered in almost all types of cancers and it has been classified as an oncogenic microRNA. Persistent HPV infection is the main etiologic agent in cervical cancer and induces genetic instability, including disruption of microRNA gene expression. In the present study, we analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells. METHODS: To identify that c-Fos and c-Jun regulate the expression of miR-21 we performed RT-qPCR and western blot assays. We analyzed the interaction of AP-1 with miR-21 promoter by EMSA and ChIP assays and determined the mechanism of its regulation by reporter construct plasmids. We identified the nuclear translocation of c-Fos and c-Jun by immunofluorescence microscopy assays. RESULTS: We demonstrated that c-Fos and c-Jun proteins are expressed and regulate the expression of miR-21 in cervical cancer cells. DNA sequence analysis revealed the presence of AP-1 DNA-binding sites in the human miR-21 promoter region. EMSA analyses confirmed the interactions of the miR-21 upstream transcription factor AP-1. ChIP assays further showed the binding of c-Fos to AP-1 sequences from the miR-21 core promoter in vivo. Functional analysis of AP-1 sequences of miR-21 in reporter plasmids demonstrated that these sequences increase the miR-21 promoter activation. CONCLUSIONS: Our findings suggest a physical interaction and functional cooperation between AP-1 transcription factor in the miR-21 promoter and may explain the effect of AP-1 on miR-21 gene expression in cervical cancer cells.
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Resumen: Introducción: El soporte vital extracorpóreo (ECLS - por sus siglas en inglés extra-corporeal life support) se aplica exitosamente en neonatos con insuficiencia respiratoria aguda (IRA). Las dificultades técnicas, los costos y los resultados desalentadores confinaron a esta técnica como última estrategia en adultos. Nuestro objetivo es reportar nuestra experiencia con ECLS en adultos. Material y métodos: Se analizaron pacientes adultos tratados con ECLS entre febrero de 2002 y enero de 2012. Se recolectaron variables demográficas y cardiopulmonares. Los datos son expresados como mediana (rango). Se analizaron las diferencias entre los pacientes afectados con IRA aislada y con síndrome cardiopulmonar por Hantavirus (SCPH) con test U de Mann Whitney y se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Se aplicó ECLS a15 pacientes. Cinco venoarteriales (VA), siete venovenoso (V-V) y tres asistencias pulmonares extracorpóreas sin bomba (P-ELA). Se describen variables demográficas, cardiopulmonares, diagnóstico, tiempo en ECLS y los desenlaces. Los días en ventilación mecánica (VM), la estadía en UCI y hospital fueron: 17 (4-49), 38 (4-93) y 46 (4-102) días respectivamente. Siete de los 15 pacientes fallecieron (47%). Dos pacientes murieron por shock séptico por bacilos Gram negativos después de un ECLS exitoso. La única diferencia estadísticamente significativa entre los pacientes con IRA aislada (ECLS-VV venovenosa o P-ELA) y los pacientes con SCPH (ECLS-VA venoarterial) fue el lactato al ingreso (p < 0.05). Conclusión: ECLS es una estrategia útil como rescate de adultos con IRA refractaria a estrategias de VM avanzada. El progreso en los equipos y el uso de algoritmos en la toma de decisiones han contribuido a reducir la morbimortalidad.
Abstract: Introduction: Extra-corporeal life support (ECLS) is an established technique for neonates with acute respiratory failure (ARF). Technical difficulties, expense and discouraging outcomes explains its confinement to a last resource tool for adults with ARF. Our objective is report the experience with adult ECLS in two hospitals. Material and methods: All consecutive adult patients treated with different ECLS techniques from 2002 to 2012 were analyzed. Demographic and cardiopulmonary variables were collected. Data are expressed as median (range). The differences between patients affected with ARF isolated and patients with hantavirus cardiopulmonary syndrome was obtained with Mann Whitney U test and a value of p < 0.05 was considered statistically significant. Results: Fifteen patients received ECLS. Five were veno-arterial (VA), 7 veno-venous (VV), and 3 pumpless extracorporeal lung assist (P-ELA). Demographic, cardiopulmonary variables, diagnosis, time on ECLS and outcome are described. Mechanical ventilation (MV), ICU and hospital stay were 17 (4-49), 38 (4-93) and 46 (4-102) days respectively. All patients who required VA-ECLS were affected for Hanta cardiopulmonary syndrome. Seven of fifteen patients died. Two out of five VA-ECLS suffered some degree of lower extremity (arterial cannulation) compartmental syndrome and a mild abnormal gait sequel affected them. Vascular accesses and bleeding were not a concern. Two patients died due to septic shock from gram negative bacilli after leaving ECLS. Conclusion: ECLS for catastrophic ARF in adults is useful therapeutic option to rescue patients who do not respond to conventional MV strategies. The progress in technical devices, use an algorithm to medical decision making contribute to reducing morbidity and mortality.
Resumo: Introdução: O suporte de vida extracorpórea (ECLS) é usado com sucesso em neonatos com insuficiência respiratória aguda (IRA). As dificuldades técnicas, custos e resultados decepcionantes confinaram a esta técnica como última estratégia em adultos. Nosso objetivo é relatar nossa experiência com ECLS em adultos. Métodos: Foram analisados pacientes adultos tratados com ECLS entre 2002 e 2012. Foram recolhidas as variáveis demográficas e cardiopulmonares. Os dados são expressos em mediana (desvio padrão). As diferenças entre os pacientes com IRA isolada e com síndrome cardiopulmonar por Hantavírus foi analisada com o teste U de Mann Whitney e foi considerou um valor estatisticamente significativo p < 0.05. Resultados: Quinze pacientes receberam ECLS. Cinco veno-arteriais (VA), 7 veno-venosas (V-V) e trêis asssistências pulmonares extracorpóreas sem bomba (P-ELA). Se descrevem variáveis demográficas, cardiopulmonar, diagnóstico, tempo no ECLS e os resultados. Os dias de ventilação mecânica (VM), tempo de UTI e hospitalar foram: 17 (4-49), 38 (4-93) e 46 (4-102) dias respectivamente. Sete dos quinze pacientes morreram (47%). Dois pacientes morreram com choque séptico por bacilos gram negativos depois de um ECLS exitoso. A única diferença estatisticamente significativa entre os pacientes com IRA isolada (ECLS-VV ou P-ELA) e pacientes com SCPH (ECLS-VA) foi o lactato na admissão (p < 0.05). Conclusão: O ECLS é uma estratégia útil como resgate de adultos com IRA refractária a estratégias de VM avançada. O progresso dos equipamentos e o uso de algoritmos na tomada de decisões têm ajudado a reduzir a morbimortalidade.
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BACKGROUND: The success of orthotopic liver transplantation (OLT) has resulted in its widespread use for different liver diseases. AIM: To report our 8 years experience with adult OLT at Clinica Alemana de Santiago. PATIENTS AND METHODS: In all transplantations done at the center, we recorded patient's overall data and survival, postoperative medical and surgical complications and causes of death. RESULTS: Between November 1993 and September 2001, 51 consecutive OLT were performed in 44 patients (22 females, median age 45 years old). Thirty eight patients presented with chronic and 6 with acute or sub-acute liver failure. Cryptogenic cirrhosis and hepatitis C infection were the most common causes for OLT. Postoperative bleeding and extrahepatic biliary complications were seen in 17.6 and 21.5% of cases respectively. Acute rejection, bacterial infections, CMV infection or disease and post OLT hemodialysis were the most common medical complications (51, 31, 19.6 and 19.6% of cases respectively). The overall 1 and 5 years survival rates were 80% and 73% respectively. Considering exclusively the last 22 OLT performed since January 1999, the 1 year survival rate has improved to 91%. CONCLUSIONS: Liver transplantation in Chile provides a good long term survival with acceptable morbidity, due to a multidisciplinary approach management. The survival rates have improved over the last few years probably due to better surgical techniques, ICU care and immunosuppression. These overall results are comparable with those from other Centers in developed countries.
