Polymeric particles are ideal drug delivery systems due to their cellular uptake-relevant size. Microparticles could be developed for direct injection of drug formulations into a diseased site, such ...as a tumor, allowing for drug retention and slow drug exposure over time through sustained release mechanisms.
silk fibroin has shown promise as a biocompatible biomaterial both in research and the clinic. Silk has been previously used to make particles using an emulsion-based method with poly(vinyl alcohol) (PVA). In this study, polydimethylsiloxane-based microfluidic devices were designed, fabricated, and characterized to produce silk particles through self-association of silk when exposed to PVA. Three main variables resulted in differences in particle size and size distribution, or polydispersity index (PDI). Utilizing a co-flow microfluidic device decreased the PDI of the silk particles as compared to an emulsion-based method (0.13 versus 0.65, respectively). With a flow-focusing microfluidics device, lowering the silk flow rate from 0.80 to 0.06 mL/h resulted in a decrease in the median particle size from 6.8 to 3.0 μm and the PDI from 0.12 to 0.05, respectively. Lastly, decreasing the silk concentration from 12% to 2% resulted in a decrease in the median particle size from 5.6 to 2.8 μm and the PDI from 0.81 to 0.25, respectively. Binding and release of doxorubicin, a cytotoxic drug commonly used for cancer treatment, with the fabricated silk particles was evaluated. Doxorubicin loading in the silk particles was approximately 41 µg/mg; sustained doxorubicin release occurred over 23 days. When the cytotoxicity of the released doxorubicin was tested on KELLY neuroblastoma cells, significant cell death was observed. To demonstrate the potential for internalization of the silk particles, both KELLY and THP-1-derived macrophages were exposed to fluorescently labelled silk particles for up to 24 h. With the macrophages, internalization of the silk particles was observed. Additionally, THP-1 derived macrophages exposure to silk particles increased TNF-α secretion. Overall, this microfluidics-based approach for fabricating silk particles utilizing PVA as a means to induce phase separation and silk self-assembly is a promising approach to control particle size and size distribution. These silk particles may be utilized for a variety of biomedical applications including drug delivery to multiple cell types within a tumor microenvironment.
Rational design and robust formulation processes are critical for optimal delivery of mRNA by lipid nanoparticles (LNPs). Varying degrees of heterogeneity in mRNA-LNPs can affect their biophysical ...and functional properties. Given the profound complexity of mRNA-LNPs, it is critical to develop comprehensive and orthogonal analytical techniques for a better understanding of these formulations. To this end, we developed a robust ultracentrifugation method for density-based separation of subpopulations of mRNA-LNPs. Four LNP formulations encapsulating human erythropoietin (hEPO) with varying functionalities were synthesized using two ionizable lipids, A and B, and two helper lipids, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE), along with cholesterol and DMG-PEG-2K. Upon ultracentrifugation on a sucrose gradient, a distinct pattern of “fractions” was observed across the gradient, from the less dense topmost fraction to the increasingly denser bottom fractions, which were harvested for comprehensive analyses. Parent LNPs, A-DOPE and B-DOPE, were resolved into three density-based fractions, each differing significantly in the hEPO expression following intravenous and intramuscular routes of administration. Parent B-DEPE LNPs resolved into two density-based fractions, with most of the payload and lipid content being attributed to the topmost fraction compared to the lower one, indicating some degree of heterogeneity, while parent A-DEPE LNPs showed remarkable homogeneity, as indicated by comparable in vivo potency, lipid numbers, and particle count among the three density-based fractions. This study is the first to demonstrate the application of density gradient-based ultracentrifugation (DGC) for a head-to-head comparison of heterogeneity as a function of biological performance and biophysical characteristics of parent mRNA-LNPs and their subpopulations.
Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an ...mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.
Graphical Abstract
Introducción: La hidradenitis supurativa (HS) es un desorden inflamatorio crónico de la piel que involucra disfunción infundibulofolicular y una respuesta inmune anormal. Presenta un pico de ...incidencia entre la segunda y tercera década de la vida y se presenta clínicamente como lesiones supurativas dolorosas, crónicas y recurrentes en las áreas intertriginosas, que evolucionan a tractos sinuosos y bandas de cicatriz deformante con marcada afectación de la calidad de vida. El presente artículo es una completa revisión del estado del arte de la HS, en esta primera parte se abordará epidemiología, factores de riesgo, comorbilidades y fisiopatología. Materiales y métodos: Para esta revisión narrativa se realizó una completa búsqueda de la literatura en 3 bases de datos (Pubmed, Science Direct, EMBASE), desde 2001 hasta 2020, incluyendo artículos publicados en inglés y en español. Resultados: Se incluyeron 110 artículos publicados desde 2001 hasta 2020, los cuales fueron revisados en texto completo. Conclusión: La hidradenitis supurativa es una enfermedad dermatológica compleja con una prevalencia importante a nivel mundial. Los factores de riesgo son diversos al igual que las comorbilidades asociadas que se han descrito y que merecen total atención para un abordaje integro. Los avances en el entendimiento de su fisiopatología son importantes y han permitido una mayor comprensión de la enfermedad.
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that involves infundibulofollicular dysfunction and abnormal immune response. It has a peak incidence between the second and third decades of life and clinically presents as painful, chronic, and recurrent suppurative lesions in the intertriginous areas, which evolve into sinuous tracts and deforming scar bands with a remarkable impact on quality of life. This article is a comprehensive review of the state of the art of HS. This first part includes epidemiology, risk factors, comorbidities, and pathophysiology. Materials and methods: For this narrative review, a complete literature search was carried out in 3 databases (Pubmed, Science Direct, EMBASE), from 2001 to 2020, including articles published in English and Spanish. Results: 110 articles published from 2001 to 2020 were included and reviewed in full text. Conclusion: Hidradenitis suppurativa is a complex dermatological disease with a significant prevalence worldwide. The risk factors and the associated comorbidities are diverse and deserve full attention for a comprehensive approach. Advances in the understanding of its pathogenesis are relevant to achieving a greater comprehension of the disease.
Tendencias en dermatología: aportes de un grupo de estudio Cruz, Adriana R.; Luna, Johanna; Montoya, Natalia ...
Revista de la Asociacion Colombiana de Dermatologia y Cirugia Dermatologica,
04/2020, Letnik:
27, Številka:
4
Journal Article
Odprti dostop
Un componente fundamental en nuestro ejercicio profesional es el de mantenernos actualizados, de forma continua y permanente, en beneficio de los pacientes, colegas y nosotros mismos. Las fuentes de ...información actualmente son numerosas y debemos ser muy cuidadosos al recibir noticias o comunicaciones acerca de nuevos métodos de diagnóstico, prevención o, más aún, tratamiento de las diferentes condiciones o enfermedades de la piel. Es por esto por lo que este grupo de colegas ha tomado temas nuevos o controversiales de eventos académicos de dermatología y ha revisado la literatura correspondiente. Con el propósito de contribuir a la actualización de los colegas dermatólogos, decidimos hacer un corto resumen de las novedades en temas como melasma, láser vaginal, vitiligo, dermatitis atópica, celulitis, acné, defectos pigmentarios, uso de cannabinoides en piel y dermatoscopia.
To estimate the prevalence of musculoskeletal (MSK) disorders and to describe predicting variables associated with rheumatic diseases in 5 regions of México.
This was a cross-sectional, ...community-based study performed in 5 regions in México. The methodology followed the guidelines proposed by the Community Oriented Program for the Control of the Rheumatic Diseases (COPCORD). A standardized methodology was used at all sites, with trained personnel following a common protocol of interviewing adult subjects in their household. A "positive case" was defined as an individual with nontraumatic MSK pain of > 1 on a visual analog pain scale (0 to 10) during the last 7 days. All positive cases were referred to internists or rheumatologists for further clinical evaluation, diagnosis, and proper treatment.
The study included 19,213 individuals; 11,602 (68.8%) were female, and their mean age was 42.8 (SD 17.9) years. The prevalence of MSK pain was 25.5%, but significant variations (7.1% to 43.5%) across geographical regions occurred. The prevalence of osteoarthritis was 10.5%, back pain 5.8%, rheumatic regional pain syndromes 3.8%, rheumatoid arthritis 1.6%, fibromyalgia 0.7%, and gout 0.3%. The prevalence of MSK manifestations was associated with older age and female gender.
The prevalence of MSK pain in our study was 25.5%. Geographic variations in the prevalence of MSK pain and specific diagnoses suggested a role for geographic factors in the prevalence of rheumatic diseases.
Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based ...coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment for many students around the world simultaneously. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeating standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were hosted in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.
STEM education; Cloud laboratories; Remote education; Biology education; Latinx; Hispanics; Undeserved communities
This article presents the design of a pedagogical method to produce interactive learning objects that allow users to learn about new statistical process control techniques, such as Data Mining, in ...order to address the curricular needs of college students enrolled in academic programs related to quality engineering. Acquiring skills in this type of tools enables students to have a more competitive profile to work at different organizations.
BACKGROUNDThe overall estimated prevalence of rheumatoid arthritis (RA) in Mexico is 1.6%, but there are major variations in different geographic areas of the country.
OBJECTIVEThis study aimed to ...determine the impact of individual and regional variables on the geographic distribution of RA in Mexico.
METHODSThis multilevel analysis used data from a cross-sectional study that investigated the prevalence of RA among 19,213 individuals older than 18 years throughout 5 geographic regions in Mexico. Logistic regression models were used to determine predictors of RA, including individual and regional variables as well as cultural factors. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were determined.
RESULTSThe prevalence of RA varied from 0.77% to 2.8% across the 5 regions. Individual factors associated with RA were sex (OR, 2.32; 95% CI, 1.74–3.07), previous medical diagnosis of RA (OR, 3.32; 95% CI, 2.19–2.20), disability (OR, 2.07; 95% CI, 1.48–2.93), and the 56- to 65-year age group (OR, 1.95; 95% CI, 1.08–3.74). The regional factor of speaking an indigenous language had an OR of 2.27 (95% CI, 1.13–4.55).
CONCLUSIONSVarious individual and regional factors were associated with variations in the prevalence of RA in the Mexican population.
Objetivo Priorizar los grupos de enfermedades, poblacion y metodos de analisis en salud publica segun las preferencias de los actores de la red de conocimiento del Observatorio Nacional de Salud. ...Metodo Se utilizo el metodo de Analisis Conjunto (AC), que consiste en la construccion de un modelo factorial completo tomando una muestra aleatoria de sujetos que deben, segun un orden de importancia pre-establecido, identificar las preferencias de los atributos de determinado constructo. Los actores de la red de conocimiento que participaron fueron profesionales de universidades publicas, miembros de EPS, IPS, secretarias de salud departamental, organizaciones sin animo de lucro enfocadas en salud, centros de investigacion especializados, de alcaldias, y corporaciones. Resultados Los grupos de enfermedades prioritarios fueron: trastornos mentales y del comportamiento (13,8 %), enfermedades cardiovasculares y circulatorias (13 %), neoplasmas (10 %) Diarrea, infecciones respiratorias, meningitis y otras enfermedades infecciosas comunes (6,7 %) y deficiencias nutricionales (6,3 %). Los criterios de priorizacion preferidos fueron la carga de enfermedad derivada y la dinamica epidemiologica del alto impacto. La informacion prioritaria de analisis fue la de determinantes sociales. El grupo poblacional de mayor preferencia fue la poblacion general. Conclusiones Se evidencio que los participantes perciben como prioritarias tanto las enfermedades cronicas como infecciosas concordante con la transicion epidemiologica del pais. La prioridad mas sentida del sistema sanitario colombiano es la construccion de capacidad del recurso humano y el fortalecimiento del sistema de vigilancia en las regiones para la toma de decisiones en salud publica. Palabras Clave: Agenda de prioridades en salud, salud publica, Colombia, metodos (fuente: DeCS, BIREME). Objective To prioritize diseases, population and methods of analysis in public health according to the preferences of the stakeholders of the knowledge network of the National Health Observatory. Method The Conjoint Analysis methodology (AC) was used; it consists on the construction of a complete factorial model taking a random sample of subjects that must identify the preferences of the attributes of a given construct according to a pre-established order of importance. The stakeholders of the knowledge network who participated were professionals from public universities, members of health promotion entities, health provision services, health departments, non-profit health organizations, specialized research centers, mayor's offices, and corporations. Results The groups of priority diseases were mental and behavioral disorders (13.8 %), cardiovascular and circulatory diseases (13 %), neoplasms (10 %), diarrhea, respiratory infections, meningitis and other common infectious diseases (6.7 %), and nutritional deficiencies (6.3 %). The preferred prioritization criteria were the burden of disease and high-impact epidemiological dynamics. The analysis of priority information was the analysis of social determinants. The most preferred population was the general population. Conclusions Participants perceive both chronic and infectious diseases as a priority, which is consistent with the epidemiological transition of the country. The priority for the Colombian health system is to strengthen the capacity of human resources and the surveillance system in different areas to have a better decision-making process in relation to public health. Key Words: Health priority, methods, public health, Colombia (source: MeSH, NLM).
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