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PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , América Latina/epidemiologia , ConsensoRESUMO
Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.
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Clima , Orchidaceae , Austrália , Filogenia , Filogeografia , Orchidaceae/genéticaRESUMO
OBJECTIVES: This study investigates the role of retinol binding protein 4 (RBP4) in an articular context. RBP4, a vitamin A transporter, is linked to various metabolic diseases. METHODS: Synovial fluid RBP4 levels were assessed in crystalline arthritis (CA) patients using ELISA. RBP4's impact on articular cell types was analysed in vitro through RT-PCR and flow cytometry. Proteomic analysis was conducted on primary human osteoarthritis chondrocytes (hOACs). RESULTS: Synovial fluid RBP4 concentrations in CA patients correlated positively with glucose levels and negatively with synovial leukocyte count and were elevated in hypertensive patients. In vitro, these RBP4 concentrations activated neutrophils, induced the expression of inflammatory factors in hOACs as well as synoviocytes, and triggered proteomic changes consistent with inflammation. Moreover, they increased catabolism and decreased anabolism, mitochondrial dysfunction, and glycolysis promotion. Both in silico and in vitro experiments suggested that RBP4 acts through TLR4. CONCLUSIONS: This study identifies relevant RBP4 concentrations in CA patients' synovial fluids, linking them to hypertensive patients with a metabolic disruption. Evidence is provided that RBP4 acts as a DAMP at these concentrations, inducing robust inflammatory, catabolic, chemotactic, and metabolic responses in chondrocytes, synoviocytes, and neutrophils. These effects may explain RBP4-related metabolic diseases' contribution to joint destruction in various rheumatic conditions like CA.
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BACKGROUND: The burden of maternal morbidity in neonatal outcomes can vary with the adequacy of healthcare provision and tool implementation to improve monitoring. Such information is lacking in Latin American countries, where the decrease in severe maternal morbidity and maternal death remains challenging. OBJECTIVES: To determine neonatal outcomes according to maternal characteristics, including different degrees of maternal morbidity in Latin American health facilities. METHODS: This is a secondary cross-sectional analysis of the Perinatal Information System (SIP) database from eight health facilities in five Latin American and Caribbean countries. Participants were all women delivering from August 2018 to June 2021, excluding cases of abortion, multiple pregnancies and missing information on perinatal outcomes. As primary and secondary outcome measures, neonatal near miss and neonatal death were measured according to maternal/pregnancy characteristics and degrees of maternal morbidity. Estimated adjusted prevalence ratios (PRadj) with their respective 95% CIs were reported. RESULTS: In total 85,863 live births were included, with 1,250 neonatal near miss (NNM) cases and 695 identified neonatal deaths. NNM and neonatal mortality ratios were 14.6 and 8.1 per 1,000 live births, respectively. Conditions independently associated with a NNM or neonatal death were the need for neonatal resuscitation (PRadj 16.73, 95% CI [13.29-21.05]), being single (PRadj 1.45, 95% CI [1.32-1.59]), maternal near miss or death (PRadj 1.64, 95% CI [1.14-2.37]), preeclampsia (PRadj 3.02, 95% CI [1.70-5.35]), eclampsia/HELPP (PRadj 1.50, 95% CI [1.16-1.94]), maternal age (years) (PRadj 1.01, 95% CI [<1.01-1.02]), major congenital anomalies (PRadj 3.21, 95% CI [1.43-7.23]), diabetes (PRadj 1.49, 95% CI [1.11-1.98]) and cardiac disease (PRadj 1.65, 95% CI [1.14-2.37]). CONCLUSION: Maternal morbidity leads to worse neonatal outcomes, especially in women suffering maternal near miss or death. Based on SIP/PAHO database all these indicators may be helpful for routine situation monitoring in Latin America with the purpose of policy changes and improvement of maternal and neonatal health.
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Morte Perinatal , Complicações na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos Transversais , Ressuscitação , Mortalidade Infantil , Mortalidade Materna , Sistemas de Informação , Complicações na Gravidez/epidemiologiaRESUMO
Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1ß for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.
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Cerveja , Condrócitos , Polifenóis , Polifenóis/farmacologia , Condrócitos/efeitos dos fármacos , Células Cultivadas , Inflamação , Animais , Camundongos , Sobrevivência Celular , Diferenciação Celular , Simulação de Acoplamento Molecular , Receptores de EstrogênioRESUMO
Abstract The biomedical field has benefited greatly from the influx of information and communication technologies. Over the last few years, enormous strides have been made in organizing, structuring and seeking information, facilitating this task, as evidenced by the various databases and search engines. In this context, metasearchers are a powerful tool for optimizing the effectiveness of searches for scientific evidence and, therefore, represent an added value both in clinical practice as well as in the research setting. This article is aimed at healthcare workers. The purpose is to update the basic concepts about metasearchers, their generalities and the main characteristics of the most outstanding ones in the biomedical field. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2587).
Resumen El área biomédica ha recibido grandes beneficios con el influjo de las tecnologías de la información y la comunicación. En los últimos años, en lo que respecta a organizar, estructurar y buscar información, se han visto enormes avances que facilitan esta labor y las diversas bases de datos y los motores de búsqueda dan cuenta de ello. En este contexto, los metabuscadores constituyen una herramienta poderosa para optimizar la eficacia de las búsquedas de evidencia científica y, por ende, representan un valor agregado tanto en la práctica clínica como en el escenario de la investigación. Este artículo está dirigido al personal de la salud. El propósito es actualizar conceptos básicos en cuanto a los metabuscadores, sus generalidades y las principales características de los más destacados en el área biomédica. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2587).
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Introduction: Qualitative research seeks to understand the meaning and perspective of individuals and investigates considering the context. This paradigm allows the interpretation and study of phenomena from their own complexity. In public health, qualitative research has gained ground, as it allows the study of subjective aspects of the health-disease process. Objective: To describe and analyze qualitative research on health issues published in Colombian journals between 2011 and 2021. Materials and methods: A descriptive study on qualitative health research published in Colombian journals between 2011 and 2021 was carried out. Results: Eighty-one articles were included. The journal with the highest number of publications was the Revista de Salud Pública (44.4%). The year with the highest production corresponded to 2019 and the main design was the fundamental theory (17.3%). In 79% of the articles, women were the main author and nursing was the most frequent profession of undergraduate training. The most frequent topic was HIV/AIDS (12.3%), followed by cancer (11.1%). In 24.6% of the studies, a software was used for the analysis. Conclusions: Qualitative research in public health has had a variable dynamic in scientific production between 2011 and 2021. Despite its benefits, the adoption of computer programs for qualitative analysis is rare. Nursing stands out as the area that concentrates the largest number of qualitative studies in public health with contributions on topics such as COVID-19 and HIV/AIDS.
Introducción. La investigación cualitativa busca comprender el sentido y la perspectiva de los individuos e indaga teniendo en cuenta el contexto. Este paradigma permite la interpretación y el estudio de los fenómenos desde su propia complejidad. En salud pública, la investigación cualitativa ha ganado terreno, pues permite estudiar aspectos subjetivos del proceso salud-enfermedad. Objetivo. Describir y analizar las investigaciones cualitativas en temas de salud pública publicadas en revistas colombianas entre el 2011 y el 2021. Materiales y métodos. Se llevó a cabo un estudio descriptivo sobre las investigaciones cualitativas en salud pública publicadas en revistas colombianas entre el 2011 y el 2021. Resultados. Se incluyeron 81 artículos. La revista con mayor cantidad de publicaciones fue la Revista de Salud Pública (44,4 %). El año con mayor producción correspondió al 2019 y el principal diseño fue la teoría fundamentada (17,3 %). En el 79 % de los artículos, las mujeres fueron el autor principal y la enfermería constituyó la profesión más frecuente de formación de pregrado. El tema más frecuente fue el VIH/sida (12,3 %), seguido por el cáncer (11,1%). En el 24,6 % de los estudios, se utilizó un software para el análisis. Conclusiones. Las investigaciones cualitativas en salud pública han tenido una dinámica variable en la producción científica entre el 2011 y el 2021. Pese a sus bondades, la adopción de programas informáticos para el análisis cualitativo es escasa. La enfermería se destaca como el área que concentra la mayor cantidad de estudios cualitativos en salud pública con aportes en temáticas como COVID-19 y VIH/sida.
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COVID-19 , Humanos , Estudos RetrospectivosRESUMO
Introducción: el estudio se desarrolló en el contexto de un programa de salud familiar y comunitaria de una universidad de Bogotá (Colombia), del cual participan los estudiantes de Medicina. El objetivo fue comprender los significados y sentidos que los estudiantes otorgan a la práctica de salud familiar y comunitaria en el barrio El Codito, ubicado en la localidad de Usaquén al nororiente de Bogotá. Materiales y métodos: la investigación es un estudio cualitativo de tipo fenomenológico. Se realizaron entrevistas semiestructuradas a ocho estudiantes de medicina pertenecientes a un programa universitario de salud familiar y comunitaria en Bogotá. Resultados: del proceso de análisis emergieron cuatro categorías: a) realidad y territorio; b) institucionalidad y salud familiar y comunitaria; c) agencia y proyección profesional, y d) comunicación, escucha y reconocimiento del otro. Se evidenciaron narrativas embebidas de experiencias significativas, dificulta- des y retos. Se destaca el rol participativo del estudiante en la interacción y comunicación con la familia. Conclusiones: la experiencia da cuenta de un proceso dinámico de donde emergen vivencias que confrontan a los estudiantes. Esta experiencia refleja aprendizajes y desafíos de carácter multidimensional, en especial por la vulnerabilidad del sector. De dicho proceso surge el reconocimiento de otras realidades, el autorreconocimiento y la proyección del estudiante como agente social y futuro profesional en medicina.
Introduction: This study was developed in accordance to the family and community health program at Bogotá University. The objective of this study was to understand the experiences of students in family and community health practice in the El Codito neighborhood of northeast Bogotá (Colombia) in the town of Usaquen. Materials and methods: Medical students of the university participated in this qualitative phenomenological study. Eight semi-structured interviews were conducted with the students who participated in the family and community health program at Bogotá University (Colombia). Results: Four categories emerged from the analysis process: reality and territory, institutionality and family and community health, agency and professional projection, and communication; listening; and recognition of other. Embedded narratives of significant experiences, difficulties, and multidimensional challenges were evident. The student's role in the interaction and communication with families was highlighted. Self-recognition, recognition of other realities, and the student's projection as a future professional emerged from this process. Conclusions: The participation of students was a dynamic process from which experiences that confront students emerged. This experience reflected multidimensional learning and challenges due to the vulnerability of this sector. This process resulted in the recognition of other realities, self-recognition, and the student's projection as a social agent and future professional in medicine.
Introdução: este estudo foi desenvolvido no contexto de um programa de saúde familiar e comunitária de uma universidade de Bogotá, do qual participam estudantes de medicina. O objetivo do estudo foi compreender os significados e sentidos que os alunos atribuem à prática de saúde familiar e comunitária no bairro El Codito, localizado no nordeste de Bogotá (Colômbia). Materiais e métodos: para a pesquisa, foi realizado um estudo qualitativo de tipo fenomenológico. Foram realizadas oito entrevistas semiestruturadas com estudantes de medicina pertencentes a um programa universitário de saúde familiar e comunitária em Bogotá (Colômbia). Resultados: do processo de análise emergiram quatro categorias: realidade e território; institucionalidade e saúde familiar e comunitária; agenciamento e projeção profissional; comunicação, escuta e reconhecimento do outro. Evidenciaramse narrativas embutidas de experiências significativas, dificuldades e desafios. Destaca-se o papel participativo do aluno na interação e comunicação com a família. Conclusões: a experiência dá conta de um processo dinâmico do qual emergem experiências que confrontam os alunos. Essa experiência reflete aprendizados e desafios de natureza multidimensional, especialmente devido à vulnerabilidade do setor. Deste processo decorre o reconhecimento de outras realidades, o autorreconhecimento e a projeção do aluno como agente social e futuro profissional da medicina.
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HumanosRESUMO
BACKGROUND: Knowledge about regulating transcription factors (TFs) for osteoblastogenesis from mesenchymal stem cells (MSCs) is limited. Therefore, we investigated the relationship between genomic regions subject to DNA-methylation changes during osteoblastogenesis and the TFs known to directly interact with these regulatory regions. RESULTS: The genome-wide DNA-methylation signature of MSCs differentiated to osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. During adipogenesis no CpGs passed our test for significant methylation changes. Oppositely, during osteoblastogenesis we identified 2462 differently significantly methylated CpGs (adj. p < 0.05). These resided outside of CpGs islands and were significantly enriched in enhancer regions. We confirmed the correlation between DNA-methylation and gene expression. Accordingly, we developed a bioinformatic tool to analyse differentially methylated regions and the TFs interacting with them. By overlaying our osteoblastogenesis differentially methylated regions with ENCODE TF ChIP-seq data we obtained a set of candidate TFs associated to DNA-methylation changes. Among them, ZEB1 TF was highly related with DNA-methylation. Using RNA interference, we confirmed that ZEB1, and ZEB2, played a key role in adipogenesis and osteoblastogenesis processes. For clinical relevance, ZEB1 mRNA expression in human bone samples was evaluated. This expression positively correlated with weight, body mass index, and PPARγ expression. CONCLUSIONS: In this work we describe an osteoblastogenesis-associated DNA-methylation profile and, using these data, validate a novel computational tool to identify key TFs associated to age-related disease processes. By means of this tool we identified and confirmed ZEB TFs as mediators involved in the MSCs differentiation to osteoblasts and adipocytes, and obesity-related bone adiposity.
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Células-Tronco Mesenquimais , Osteogênese , Humanos , Osteogênese/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Metilação de DNA , Diferenciação Celular/genéticaRESUMO
Introducción. La investigación cualitativa busca comprender el sentido y la perspectiva de los individuos e indaga teniendo en cuenta el contexto. Este paradigma permite la interpretación y el estudio de los fenómenos desde su propia complejidad. En salud pública, la investigación cualitativa ha ganado terreno, pues permite estudiar aspectos subjetivos del proceso salud-enfermedad. Objetivo. Describir y analizar las investigaciones cualitativas en temas de salud pública publicadas en revistas colombianas entre el 2011 y el 2021. Materiales y métodos. Se llevó a cabo un estudio descriptivo sobre las investigaciones cualitativas en salud pública publicadas en revistas colombianas entre el 2011 y el 2021. Resultados. Se incluyeron 81 artículos. La revista con mayor cantidad de publicaciones fue la Revista de Salud Pública (44,4 %). El año con mayor producción correspondió al 2019 y el principal diseño fue la teoría fundamentada (17,3 %). En el 79 % de los artículos, las mujeres fueron el autor principal y la enfermería constituyó la profesión más frecuente de formación de pregrado. El tema más frecuente fue el VIH/sida (12,3 %), seguido por el cáncer (11,1%). En el 24,6 % de los estudios, se utilizó un software para el análisis. Conclusiones. Las investigaciones cualitativas en salud pública han tenido una dinámica variable en la producción científica entre el 2011 y el 2021. Pese a sus bondades, la adopción de programas informáticos para el análisis cualitativo es escasa. La enfermería se destaca como el área que concentra la mayor cantidad de estudios cualitativos en salud pública con aportes en temáticas como COVID-19 y VIH/sida.
Introduction: Qualitative research seeks to understand the meaning and perspective of individuals and investigates considering the context. This paradigm allows the interpretation and study of phenomena from their own complexity. In public health, qualitative research has gained ground, as it allows the study of subjective aspects of the health-disease process. Objective: To describe and analyze qualitative research on health issues published in Colombian journals between 2011 and 2021. Materials and methods: A descriptive study on qualitative health research published in Colombian journals between 2011 and 2021 was carried out. Results: Eighty-one articles were included. The journal with the highest number of publications was the Revista de Salud Pública (44.4%). The year with the highest production corresponded to 2019 and the main design was the fundamental theory (17.3%). In 79% of the articles, women were the main author and nursing was the most frequent profession of undergraduate training. The most frequent topic was HIV/AIDS (12.3%), followed by cancer (11.1%). In 24.6% of the studies, a software was used for the analysis. Conclusions: Qualitative research in public health has had a variable dynamic in scientific production between 2011 and 2021. Despite its benefits, the adoption of computer programs for qualitative analysis is rare. Nursing stands out as the area that concentrates the largest number of qualitative studies in public health with contributions on topics such as COVID-19 and HIV/AIDS.
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Saúde Pública , Pesquisa Qualitativa , Artigo de Revista , Entrevista , Colômbia , Publicação PeriódicaRESUMO
It is well known that patients with attention deficit hyperactivity disorder treated with stimulants, such as methylphenidate hydrochloride (MPH), have reduced height and weight. Even though MPH has an anorexigenic effect, an additional impact of this drug on the growth plate cannot be discarded. In this study, we aimed to determine the cellular effect of MPH on an in vitro growth plate model. We tested the effects of MPH on the viability and proliferation of a prechondrogenic cell line via an MTT assay. In vitro differentiation of this cell line was performed, and cell differentiation was evaluated through the expression of cartilage- and bone-related genes as measured via RT-PCR. MPH did not alter the viability or proliferation of prechondrogenic cells. However, it reduced the expression of cartilage extracellular matrix-related genes (type II collagen and aggrecan) and increased the expression of genes involved in growth plate calcification (Runx2, type I collagen, and osteocalcin) at different phases of their differentiation process. Our results evidence that MPH upregulates genes associated with growth plate hypertrophic differentiation. This may induce premature closure of the growth plate, which would contribute to the growth retardation that has been described to be induced by this drug.
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Estimulantes do Sistema Nervoso Central , Lâmina de Crescimento , Metilfenidato , Osteogênese , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Lâmina de Crescimento/efeitos dos fármacos , Metilfenidato/efeitos adversos , Osteogênese/efeitos dos fármacos , Células CultivadasRESUMO
Osteoarthritis (OA) is hallmarked as a silent progressive rheumatic disease of the whole joint. The accumulation of inflammatory and catabolic factors such as IL6, TNFα, and COX2 drives the OA pathophysiology into cartilage degradation, synovia inflammation, and bone destruction. There is no clinical available OA treatment. Although traditional ayurvedic medicine has been using Boswellia serrata extracts (BSE) as an antirheumatic treatment for a millennium, none of the BSE components have been clinically approved. Recently, ß boswellic acid (BBA) has been shown to reduce in vivo OA-cartilage loss through an unknown mechanism. We used computational pharmacology, proteomics, transcriptomics, and metabolomics to present solid evidence of BBA therapeutic properties in mouse and primary human OA joint cells. Specifically, BBA binds to the innate immune receptor Toll-like Receptor 4 (TLR4) complex and inhibits both TLR4 and Interleukin 1 Receptor (IL1R) signaling in OA chondrocytes, osteoblasts, and synoviocytes. Moreover, BBA inhibition of TLR4/IL1R downregulated reactive oxygen species (ROS) synthesis and MAPK p38/NFκB, NLRP3, IFNαß, TNF, and ECM-related pathways. Altogether, we present a solid bulk of evidence that BBA blocks OA innate immune responses and could be transferred into the clinic as an alimentary supplement or as a therapeutic tool after clinical trial evaluations.
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BACKGROUND: Knowledge about regulating transcription factors (TFs) for osteoblastogenesis from mesenchymal stem cells (MSCs) is limited. Therefore, we investigated the relationship between genomic regions subject to DNA-methylation changes during osteoblastogenesis and the TFs known to directly interact with these regulatory regions. RESULTS: The genome-wide DNA-methylation signature of MSCs differentiated to osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. During adipogenesis no CpGs passed our test for significant methylation changes. Oppositely, during osteoblastogenesis we identified 2462 differently significantly methylated CpGs (adj. p < 0.05). These resided outside of CpGs islands and were significantly enriched in enhancer regions. We confirmed the correlation between DNA-methylation and gene expression. Accordingly, we developed a bioinformatic tool to analyse differentially methylated regions and the TFs interacting with them. By overlaying our osteoblastogenesis differentially methylated regions with ENCODE TF ChIP-seq data we obtained a set of candidate TFs associated to DNA-methylation changes. Among them, ZEB1 TF was highly related with DNA-methylation. Using RNA interference, we confirmed that ZEB1, and ZEB2, played a key role in adipogenesis and osteoblastogenesis processes. For clinical relevance, ZEB1 mRNA expression in human bone samples was evaluated. This expression positively correlated with weight, body mass index, and PPARγ expression. CONCLUSIONS: In this work we describe an osteoblastogenesis-associated DNA-methylation profile and, using these data, validate a novel computational tool to identify key TFs associated to age-related disease processes. By means of this tool we identified and confirmed ZEB TFs as mediators involved in the MSCs differentiation to osteoblasts and adipocytes, and obesity-related bone adiposity.
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Humanos , Osteogênese/genética , Células-Tronco Mesenquimais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Diferenciação Celular/genética , Metilação de DNARESUMO
The avocado fruit (Persea americana) has become a significant fruit in the human diet for its nutritional properties. However, the seed is a source of bioactive molecules and has been poorly utilized. Previously, we reported that the PaSn gene is expressed in the avocado seeds, a cysteine-rich antimicrobial peptide (GASA/Snakin), and demonstrated its antibacterial activity. In this work, we report the recombinant production of PaSn in the Escherichia coli system and evaluate its antifungal activity against plant and human pathogen fungi. The recombinant peptide showed antifungal activity at 200 µg/mL against phytopathogens Colletotrichum gloeosporioides and Fusarium oxysporum and human pathogens Candida albicans and C. glabrata. Our results demonstrate the usefulness of a prokaryotic expression system for avocado antimicrobial peptide production. In conclusion, the snakin PaSn could be helpful in the control of postharvest avocado and other fruits' fungal diseases and human fungal pathogens.
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Osteoarthritis (OA) affects more than 300 million people worldwide and it is about to become the first disabling disease. OA is characterized by the progressive degradation of the articular cartilage but is a disease of the whole joint. Articular innate immune responses (IIR) associated with tissue degradation contribute to its progression. However, no treatment is available to block these IIRs. Through data text mining and computational pharmacology, we identified two clinical available drugs, naloxone, and thalidomide, with potential inhibitory properties on toll-like receptor 4 (TLR4), a major activator of these IIR. Proteome analysis confirmed that activation of this receptor or the IL1 receptor generated OA-like and gout-like proteomic changes in human primary chondrocytes. Both compounds were found to block TLR4 complex and inhibit TLR4 and IL1R-mediated IIR in OA chondrocytes, osteoblasts, and synoviocytes. Furthermore, naloxone and thalidomide inhibitory effects involved the downregulation of the NLRP3 inflammasome pathway, which is downstream of TLR4/IL1R signaling. We demonstrated that these compounds, within a therapeutic range of concentrations, exhibited anti-inflammatory and anti-catabolic properties in joint primary OA cells without any toxic effect. This data underpins naloxone & thalidomide repurpose to treat OA-associated inflammatory responses.
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Osteoartrite , Receptor 4 Toll-Like , Humanos , Condrócitos/metabolismo , Reposicionamento de Medicamentos , Imunidade Inata , Inflamassomos/metabolismo , Naloxona/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoartrite/metabolismo , Proteoma/metabolismo , Proteômica , Receptores de Interleucina-1/metabolismo , Talidomida/farmacologia , Receptor 4 Toll-Like/metabolismo , Interleucina-1/metabolismoRESUMO
Blackberry is an economically important crop in Mexico, and its yield is substantially reduced by gray mold, a disease caused by Botrytis cinerea. One of the means to obtain B. cinerea-resistant plants is gamma irradiation. Shoot tips of in vitro-micropropagated blackberry plants (Rubus fruticosus 'Tupy') were irradiated with five doses of Cobalt-60 gamma radiation (0, 15, 30, 45, and 60 Gy) and cultured on Murashige and Skoog basal medium containing 1.0 mg l-1 benzylaminopurine and 0.06 mg l-1 indole-3-butyric acid (MSB medium). After 28 days of culture, survival was evaluated to determine mean lethal dose (LD50), and 200 shoots were further irradiated at the determined LD50 (30.8 Gy). After 28 days, the surviving shoots were micropropagated on MSB medium for 60 days. Non-irradiated shoots were screened for the in vitro selection of resistant B. cinerea, exposing them to different concentrations of sterile culture filtrate of B. cinerea (0, 2, 4, 6, 8, and 10 g l-1) for 28 days to determine mean lethal concentration (LC50), and the irradiated surviving shoots were further exposed to the determined LC50 (4.6 g l-1). Three surviving lines (rfgum5, rfgum6, and rfgum17) that did not present changes compared with the control shoots were micropropagated to obtain plantlets, which were further subjected to in vitro resistance assays using detached leaves inoculated with B. cinerea (1×103 spores ml-1). Plants of rfgum5 and rfgum6 mutant lines were highly resistant and presented similar growth to control plants. Therefore, this methodology is useful to obtain B. cinerea-resistant blackberry plants.
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El artículo describe de forma sucinta hechos claves en el discurrir histórico de la ilustración anatómica desde el siglo xv. Se realiza un breve repaso de la conexión entre el arte y la medicina en el Renacimiento, donde es clara la comunión entre médicos y artistas en torno a las disecciones anatómicas. Se resaltan algunos elementos históricos tras el origen de la profesión de ilustrador médico y se destaca, principalmente en el siglo xx, el protagonismo de algunos médicos ilustradores, aquellos que no solo han dado libertad a sus habilidades artísticas con el dibujo, sino que también han dedicado su vida al arte de la medicina.
Summary The article succinctly describes key events in the historical course of anatomical illustration since the 15th century. A brief review of the connection between art and medicine in the Renaissance period is made, where the communion of doctors and artists around anatomical dissections is clear. Some historical elements behind the origin of the profession of medical illustrator are highlighted and, mainly, the prominence in the 20th century of some medical illustrators, who have not only given freedom to their artistic skills with drawing, but also, have dedicated their lives to the art of medicine.
Assuntos
HumanosRESUMO
Internet de las cosas está transformando el mundo a pasos acelerados. Esta nueva dimensión digital permite conectar millones de objetos a Internet, lo cual representa oportunidades para recopilar todo tipo de información. Entre los nuevos aliados de la salud pública están las mascarillas inteligentes y los drones conectados a Internet para apoyar el monitoreo de casos y la vigilancia epidemiológica. También se cuenta con Internet of Drones, la robó-tica y los wearables, los cuales se incorporan a ropa y accesorios gracias a la miniaturización de sensores. Así, la nueva salud pública podrá contar con datos masivos en pro de una salud pública menos reactiva y más predictiva. El propósito de este artículo es reflexionar sobre el papel de Internet de las cosas como aliado de la salud pública en la respuesta y el control de las pandemias.
The Internet of Things is transforming the world at a rapid pace. This new digital dimension allows millions of objects to be connected to the Internet, which represents opportunities to collect all kinds of information. Among the new allies of public health are smart masks and drones connected to the internet to support case monitoring and epidemiological surveillance. There is also Internet of Drones, robotics, and wearables, which are incorporated into clothing and accessories thanks to the miniaturization of sensors. Thus, the new public health will be able to count on massive data for a less reactive and more predictive public health. The purpose of this article is to reflect on the role of the Internet of Tings as an ally of public health in the response and control of pandemics.
RESUMO
Resumen El crecimiento exponencial de la información biomédica en los últimos años, ha hecho que la tarea de mantenerse actualizado sea compleja debido a la masiva información a la que se puede acceder a través de la web. Hoy en día, conocer los fundamentos de las denominadas sinopsis de estudios primarios y su utilidad en el contexto de la práctica clínica y la medicina basada en la evidencia es de gran relevancia para la práctica diaria de estudiantes y médicos en ejercicio. El presente artículo pretende ser una herramienta tanto para quienes se inician en el mundo de la medicina basada en la evidencia como para quienes desean extender su conocimiento en torno a las sinopsis de estudios dentro del modelo piramidal de recursos de información. Los orígenes del modelo piramidal 6s se describen de forma puntual, se explica lo concerniente a las sinopsis de estudios y se aporta información sobre los principales sitios online para acceder a estos recursos. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2184).
Abstract The exponential growth of biomedical information in recent years has made the task of keeping up to date complex, due to the massive amount of information available on the web. Today, understanding the basics of the so-called synopses of primary studies and their usefulness in the context of clinical practice and evidence-based medicine, is highly relevant for the daily work of students and practicing physicians. This article aims to be a tool for both newcomers to the world of evidence-based medicine as well as those who want to broaden their knowledge of the synopses of studies within the Pyramid Model of data resources. The origin of the Pyramid Model is specifically described, the matter of study synopses is explained, and information is provided on the main online sites for accessing these resources. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2184).