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Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood-retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain-Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR.
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Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Modelos Animais de Doenças , Microglia , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Retinopatia Diabética/imunologia , Ratos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/complicações , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Retina/metabolismo , Células RAW 264.7 , Masculino , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos Endogâmicos BBRESUMO
Clostridia are abundant in the human gut and comprise families associated with host health such as Oscillospiraceae, which has been correlated with leanness. However, culturing bacteria within this family is challenging, leading to their detection primarily through 16S rRNA amplicon sequencing, which has a limited ability to unravel diversity at low taxonomic levels, or by shotgun metagenomics, which is hindered by its high costs and complexity. In this cross-sectional study involving 114 Colombian adults, we used an amplicon-based sequencing strategy with alternative markers-gyrase subunit B (gyrB) and DNA K chaperone heat protein 70 (dnaK)-that evolve faster than the 16S rRNA gene. Comparing the diversity and abundance observed with the three markers in our cohort, we found a reduction in the diversity of Clostridia, particularly within Lachnospiraceae and Oscillospiraceae among obese individuals [as measured by the body mass index (BMI)]. Within Lachnospiraceae, the diversity of Ruminococcus_A negatively correlated with BMI. Within Oscillospiraceae, the genera CAG-170 and Vescimonas also exhibited this negative correlation. In addition, the abundance of Vescimonas was negatively correlated with BMI. Leveraging shotgun metagenomic data, we conducted a phylogenetic and genomic characterization of 120 metagenome-assembled genomes from Vescimonas obtained from a larger sample of the same cohort. We identified 17 of the 72 reported species. The functional annotation of these genomes showed the presence of multiple carbohydrate-active enzymes, particularly glycosyl transferases and glycoside hydrolases, suggesting potential beneficial roles in fiber degradation, carbohydrate metabolism, and butyrate production. IMPORTANCE: The gut microbiota is diverse across various taxonomic levels. At the intra-species level, it comprises multiple strains, some of which may be host-specific. However, our understanding of fine-grained diversity has been hindered by the use of the conserved 16S rRNA gene. While shotgun metagenomics offers higher resolution, it remains costly, may fail to identify specific microbes in complex samples, and requires extensive computational resources and expertise. To address this, we employed a simple and cost-effective analysis of alternative genetic markers to explore diversity within Clostridia, a crucial group within the human gut microbiota whose diversity may be underestimated. We found high intra-species diversity for certain groups and associations with obesity. Notably, we identified Vescimonas, an understudied group. Making use of metagenomic data, we inferred functionality, uncovering potential beneficial roles in dietary fiber and carbohydrate degradation, as well as in short-chain fatty acid production.
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Microbioma Gastrointestinal , Obesidade , Humanos , Microbioma Gastrointestinal/genética , Obesidade/microbiologia , Masculino , Adulto , Feminino , Estudos Transversais , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Metagenômica/métodos , Índice de Massa CorporalRESUMO
Huntington's disease (HD) is caused by an aberrant expansion of CAG repeats in the HTT gene that mainly affects basal ganglia. Although striatal dysfunction has been widely studied in HD mouse models, other brain areas can also be relevant to the pathology. In this sense, we have special interest on the retina as this is the most exposed part of the central nervous system that enable health monitoring of patients using noninvasive techniques. To establish the retina as an appropriate tissue for HD studies, we need to correlate the retinal alterations with those in the inner brain, i.e., striatum. We confirmed the malfunction of the transgenic R6/1 retinas, which underwent a rearrangement of their transcriptome as extensive as in the striatum. Although tissue-enriched genes were downregulated in both areas, a neuroinflammation signature was only clearly induced in the R6/1 retina in which the observed glial activation was reminiscent of the situation in HD patient's brains. The retinal neuroinflammation was confirmed in the slow progressive knock-in zQ175 strain. Overall, these results demonstrated the suitability of the mouse retina as a research model for HD and its associated glial activation.
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Doença de Huntington , Camundongos , Animais , Humanos , Doença de Huntington/patologia , Camundongos Transgênicos , Gliose/genética , Gliose/patologia , Microglia/metabolismo , Doenças Neuroinflamatórias , Modelos Animais de Doenças , Corpo Estriado/metabolismo , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismoRESUMO
Introducción: El síndrome del túnel carpiano es una de las causas más frecuentes de dolor crónico, su mayor incidencia está entre la quinta y sexta década de la vida; en Colombia tiene una alta incidencia, llegando al 14 por ciento especialmente en cierto grupo de trabajadores. El abordaje terapéutico incluye tratamiento médico y quirúrgico; en la actualidad ha sido ampliamente discutida la elección entre método endoscópico y cirugía abierta como primera línea de tratamiento. Objetivo: Desarrollar una revisión acerca de los aspectos clínicos y las diferentes opciones de abordaje terapéutico del síndrome del túnel carpiano a través de una exploración de la literatura científica existente. Métodos: Se realizó una búsqueda en las bases de datos SciELO, PubMed, ScienceDirect y Lilacs con las palabras clave indexadas en el DeCS. Conclusión: El síndrome de túnel carpiano es una entidad común con un impacto clínico importante en la vida del paciente, su sintomatología y sus complicaciones afectan las actividades diarias de quien lo padece; el abordaje terapéutico de esta enfermedad se establece comúnmente de forma escalonada, el abordaje quirúrgico es un tema ampliamente discutido; sin embargo, no hay evidencia contundente que establezca una de las opciones quirúrgicas como la definitiva(AU)
Introduction: Carpal tunnel syndrome is one of the most frequent causes of chronic pain, with its highest incidence between the fifth and sixth decades of life; in Colombia, it has a high incidence, reaching 14 percent especially in a certain group of workers. The therapeutic approach includes medical and surgical treatment; currently, the choice between the endoscopic method or open surgery as the first line of treatment has been widely discussed. Objective: To develop a review of the clinical aspects and the different options of therapeutic approach for carpal tunnel syndrome, through an exploration of the existing scientific literature. Methods: A search was carried out in the SciELO, PubMed, ScienceDirect and Lilacs databases, using the keywords indexed in the DeCS. Conclusion: Carpal tunnel syndrome is a common entity with an important clinical impact on the patient's life; its symptomatology and complications affect the daily activities of those who suffer from it. The therapeutic approach to this disease is commonly established in a stepwise manner; the surgical approach is a widely discussed topic. However, there is no conclusive evidence that establishes one of the surgical options as the definitive one/AU)
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Humanos , Masculino , Feminino , Síndrome do Túnel Carpal/diagnóstico , Síndrome do Túnel Carpal/epidemiologia , Procedimentos Ortopédicos/métodosRESUMO
OBJECTIVE: To evaluate the clinical course of atopic dermatitis (AD) in adults during the COVID-19 pandemic and to evaluate their comorbidities and cardiovascular risk. METHODS: A cross-sectional study was conducted in adults with AD. Severity and control of AD, quality of life, levels of psychological stress, depression and cardiovascular risk were measured. RESULTS: Forty-two patients were included. A decrease in POEM score (11.83 vs 10.12; p=0.004) and PO-SCORAD (37.77 vs 32.49; p= 0.001) was observed in comparison to the scores at pandemic onset. The quality of life correlated with the severity of AD (p<0.0001) while the levels of stress and depression did not show association. Most patients had a low cardiovascular risk. CONCLUSIONS: The results suggest a decrease in the current severity of AD compared with severity before pandemic. Quality of life is associated with AD severity.
OBJECTIVO: Evaluar el curso clínico de pacientes adultos con dermatitis atópica durante la pandemia por COVID-19, e identificar las comorbilidades y el riesgo cardiovascular. MÉTODOS: Estudio transversal, llevado a cabo en adultos con dermatitis atópica. Se evaluó la gravedad y el control de la dermatitis, la calidad de vida, el grado de estrés psicológico, depresión y riesgo cardiovascular. RESULTADOS: Se seleccionaron 42 pacientes.Se observó una disminución en el puntaje del POEM (11.83 vs 10.12; p=0.004) y del PO-SCORAD (37.77 vs 32.49; p= 0.001) con relación al inicio de la pandemia. La calidad vida se correlacionó con la gravedad de la dermatitis atópica (p<0.0001) a diferencia de los grados de estrés y depresión. La mayoría de los pacientes tuvo riesgo cardiovascular bajo. CONCLUSIONES: Se encontró disminución de la gravedad actual de la dermatitis atópica comparada con la gravedad antes de la pandemia. La calidad de vida se asocia con la gravedad de la dermatitis atópica.
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COVID-19 , Dermatite Atópica , Humanos , Adulto , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Dermatite Atópica/psicologia , Pandemias , Qualidade de Vida , Estudos Transversais , Índice de Gravidade de DoençaRESUMO
Resumen OBJETIVO: Describir los desenlaces maternos y perinatales en embarazadas con incompatibilidad Rh D. MATERIALES Y MÉTODOS: Estudio de cohorte retrospectiva efectuado en la Unidad Materno Infantil de Medellín, Colombia, en pacientes embarazadas atendidas entre 2013 y 2018 con incompatibilidad Rh. Se realizó un muestreo no probabilístico de casos consecutivos y un análisis univariado. RESULTADOS: Se incluyeron 250 pacientes con mediana de edad de 26 años y tipo de sangre O-, que fue el más prevalente (55.2%). El 49.2% de las pacientes había tenido entre 2 y 3 embarazos previos. El 88% de las pacientes no había tenido ningún evento sensibilizante durante el embarazo. El 65.2% tuvo un reporte negativo del primer Coombs y la media de semanas de embarazo al primer Coombs fue de 28. El 48% de las pacientes recibió la inmunoglobulina G anti-D a una mediana de 28 semanas de gestación. CONCLUSIÓN: El estudio confirma datos clínicos y sociodemográficos y sugiere que se requiere fortalecer la oportunidad en la captación temprana de las pacientes para el seguimiento con el Coombs y para la indicación de la profilaxis.
Abstract OBJECTIVE: To determine the maternal and fetal outcomes in pregnant women with Rh D incompatibility. MATERIALS AND METHODS: A Retrospective cohort study carried out in the Maternal and Child Unit of Medellín, Colombia, in pregnant patients attended between 2013 and 2018. RESULTS: 250 patients were included, in which the median age was 26 years. The O- blood type was the most prevalent in pregnant women with 55.2% and 49.2% of the patients had had between 2 and 3 previous pregnancies, in addition, 88% of the patients had not presented any sensitizing event during her pregnancy. 65.2% had a negative first Coombs result and the mean gestational age of the first Coombs was 28 weeks. 48% of patients received immunoglobulin G anti D at a median gestational age of 28 weeks. CONCLUSION: The present study confirms the clinical and sociodemographic data, however it suggests that it may be necessary to strengthen the opportunity in the early recruitment of patients for follow-up with Coombs and for the indication of prophylaxis.
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Purpose: Determination and development of an effective set of models leveraging Artificial Intelligence techniques to generate a system able to support clinical practitioners working with COVID-19 patients. It involves a pipeline including classification, lung and lesion segmentation, as well as lesion quantification of axial lung CT studies. Approach: A deep neural network architecture based on DenseNet is introduced for the classification of weakly-labeled, variable-sized (and possibly sparse) axial lung CT scans. The models are trained and tested on aggregated, publicly available data sets with over 10 categories. To further assess the models, a data set was collected from multiple medical institutions in Colombia, which includes healthy, COVID-19 and patients with other diseases. It is composed of 1,322 CT studies from a diverse set of CT machines and institutions that make over 550,000 slices. Each CT study was labeled based on a clinical test, and no per-slice annotation took place. This enabled a classification into Normal vs. Abnormal patients, and for those that were considered abnormal, an extra classification step into Abnormal (other diseases) vs. COVID-19. Additionally, the pipeline features a methodology to segment and quantify lesions of COVID-19 patients on the complete CT study, enabling easier localization and progress tracking. Moreover, multiple ablation studies were performed to appropriately assess the elements composing the classification pipeline. Results: The best performing lung CT study classification models achieved 0.83 accuracy, 0.79 sensitivity, 0.87 specificity, 0.82 F1 score and 0.85 precision for the Normal vs. Abnormal task. For the Abnormal vs COVID-19 task, the model obtained 0.86 accuracy, 0.81 sensitivity, 0.91 specificity, 0.84 F1 score and 0.88 precision. The ablation studies showed that using the complete CT study in the pipeline resulted in greater classification performance, restating that relevant COVID-19 patterns cannot be ignored towards the top and bottom of the lung volume. Discussion: The lung CT classification architecture introduced has shown that it can handle weakly-labeled, variable-sized and possibly sparse axial lung studies, reducing the need for expert annotations at a per-slice level. Conclusions: This work presents a working methodology that can guide the development of decision support systems for clinical reasoning in future interventionist or prospective studies.
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Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.
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Diabetes Mellitus , Nefropatias Diabéticas , Animais , Autofagia , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Inflamassomos , Rim/metabolismo , RatosRESUMO
Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11ß-PGF2α) and 15-F2t-IsoPs (2,3-dinor-15-F2t-IsoP and 2,3-dinor-15-epi-15-F2t-IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants.
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Antioxidantes , Doenças Cardiovasculares , Adulto , Biomarcadores , F2-Isoprostanos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso , Oxilipinas , Polifenóis , Espectrometria de Massas em TandemRESUMO
Huntington's disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. It establishes an active crosstalk between peripheral tissues and the brain in different neurodegenerative diseases. This review focuses on the current knowledge of peripheral tissue effects in HD animal and cell experimental models and identifies biomarkers and mechanisms involved or affected in the progression of the disease as new therapeutic or early diagnostic options. The particular changes in serum/plasma, blood cells such as lymphocytes, immune blood cells, the pancreas, the heart, the retina, the liver, the kidney and pericytes as a part of the blood-brain barrier are described. It is important to note that several changes in different mouse models of HD present differences between them and between the different ages analyzed. The understanding of the impact of peripheral organ inflammation in HD may open new avenues for the development of novel therapeutic targets.
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Doença de Huntington , Animais , Encéfalo , Corpo Estriado , Modelos Animais de Doenças , Proteína Huntingtina/genética , Doença de Huntington/genética , Inflamação , CamundongosRESUMO
Phthalides are a group of compounds with relevant biological activities in different areas such as cytotoxicity, anti-stroke activity, neuroprotection, and inflammation, among others. In this study we designed and synthesized a series of 3-arylphthalide derivatives in order to identify their antioxidant and anti-inflammatory activities. The synthetic methodology was established in terms of atom and step economy through a dehydrative coupling reaction between 3-hydroxyphthalide and different properly functionalized arene rings. The evaluation of the antioxidant activity was performed by the ABTS assay and for the anti-inflammatory activity the inhibition of LPS-induced nitric oxide (NO) production in microglial cells Bv.2 and macrophage cells RAW 264.7 was measured. The synthesized compound 3-(2,4-dihydroxyphenyl)phthalide (5a) showed better antioxidant activity than the Trolox standard and caused strong inhibition of NO production in LPS-stimulated Bv.2 and RAW 264.7 cells. In addition, compound 5a reduced the expression of the pro-inflammatory cytokines Il1b and Il6 in RAW 264.7 cells. These results, which are the first account of the anti-inflammatory activity of 3-arylphthalides, suggest that compound 5a could be a promising candidate for more advanced anti-inflammatory studies.
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Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. In vitro approach using cell lines help to understand the mechanisms involves and allow the molecular and biochemical processes. Adult kidney (AK) explants remain an essential instrument for advancing our understanding of the molecular and cellular regulation of signalling pathways from an organotipic view with physiological system interaction integrated. AK explants from T1DM animal model (BB rat) are obtained by slicing central kidney area preserving the organ's cytoarchitecture and reproduce the classical events detected during the DN in an in vivo model such as inflammation, epithelial-mesenchymal transition (EMT) processes by the modulation of a-SMA and e-Cadherin among others which have been determined by qRT-PCR, western-blot and immunohistochemistry. In this regard, AK explants reproduce the signalling pathways involve in DN progression (proinflammatory NFkB and inflammasome complex). This work demonstrates AK explants is a physiological experimental approach for studying the development and progression of DN. Furthermore, the inflammatory processes in AK explants under a diabetic environment and/or BB rats could be modulated by potential treatments for DN.
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Diabetes Mellitus , Nefropatias Diabéticas , Animais , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Fibrose , Humanos , Rim/metabolismo , NF-kappa B , RatosRESUMO
During Type 1 Diabetes Mellitus (T1DM) progression, there is chronic and low-grade inflammation that could be related to the evolution of the disease. We carried out a systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers such as interleukin-1 beta (IL-1ß) is significantly different among patients with or without T1DM, in gender, management of the T1DM, detection in several biological fluids, study design, age range, and glycated hemoglobin. We searched PubMed, Embase, Web of Science, and Scopus databases, and 26 relevant studies (2186 with T1DM, 2047 controls) were included. We evaluated the studies' quality using the Newcastle−Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Compared with controls, IL-1ß determined by immunoassays (pooled standardized mean difference (SMD): 2.45, 95% CI = 1.73 to 3.17; p < 0.001) was significantly elevated in T1DM. The compared IL-1ß levels in patients <18 years (SMD = 2.81, 95% CI = 1.88−3.74) was significantly elevated. The hemoglobin-glycated (Hbg) levels in patients <18 years were compared (Hbg > 7: SMD = 5.43, 95% CI = 3.31−7.56; p = 0.001). Compared with the study design, IL-1ß evaluated by ELISA (pooled SMD = 3.29, 95% CI = 2.27 to 4.30, p < 0.001) was significantly elevated in T1DM patients. IL-1ß remained significantly higher in patients with a worse management of T1DM and in the early stage of T1DM. IL-1ß levels determine the inflammatory environment during T1DM.
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Resumen La enfermedad cardiovascular sigue siendo la principal causa de muerte en el mundo. Las mujeres presentan un factor protector frente a esta durante la edad reproductiva debido al efecto de los estrógenos sobre el endotelio vascular, propio de esta etapa de la vida; posteriormente, la perimenopausia y la posmenopausia dan lugar a estados de hipoestrogenemia que generan un incremento en el riesgo de enfermedad cardiovascular y muerte por esta causa. En tal sentido, la terapia hormonal es un pilar fundamental para el tratamiento de los síntomas vasomotores en la menopausia; además, tiene impacto positivo en otros desenlaces, como el riesgo cardiovascular, la protección ósea y la depresión. Se presenta un compendio de conceptos respecto a la menopausia y el riesgo cardiovascular; aspectos históricos y medidas de tratamiento basadas en la terapia hormonal.
Abstract Cardiovascular disease continues to be the main cause of death in the world. Women present a protective factor against it during the reproductive age due to the effect of estrogens on the vascular endothelium typical of this stage of life; later, perimenopause and post-menopause give rise to hypoestrogenemia states that generate an increased risk of cardiovascular disease and death from this cause. Hormone replacement therapy is a fundamental pillar for the treatment of vasomotor symptoms in menopause, it also has a positive impact on other outcomes such as cardiovascular risk, bone protection, depression, among other pathologies. We present a compendium of concepts regarding menopause and cardiovascular risk; historical aspects and treatment measures based on hormone replacement therapy.
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Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A-C (2-4), and ruguloptones A-F (6-10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2-10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In anti-inflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW 264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines.
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Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Phaeophyceae , Animais , Anti-Inflamatórios/química , Organismos Aquáticos , Diterpenos/química , Camundongos , Células RAW 264.7/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Introducción: La enfermedad mínima residual es la permanencia de células leucémicas residuales en niveles subclínicos luego de la remisión de la enfermedad. Esta condición incrementa el riesgo de recaída y mortalidad. Objetivo: Caracterizar factores clínicos y moleculares de pacientes con leucemias agudas y enfermedad mínima residual detectada por citometría de flujo en una institución de alta complejidad de la ciudad de Medellín, Colombia durante los años 2015 - 2017. Metodología: Este es un estudio descriptivo retrospectivo, que incluyó pacientes con leucemia diagnosticada por citometría de flujo. Se realizó un muestreo no probabilístico de casos consecutivos. La información recolectada fue digitada en una base de datos en Excel, y el análisis se realizó a través del programa IBM SPSS Versión 24, empleando según la naturaleza de cada variable frecuencias absolutas y relativas, promedio y desviación estándar o mediana y rangos intercuartílicos según su distribución. Resultados: Se incluyó un total de 60 pacientes con predominio del sexo masculino 63,3 por ciento (38). El diagnóstico más frecuente fue la leucemia linfoide 78,3 por ciento (47). Del total de pacientes incluidos, 36,6 por ciento (22) fue positivo para enfermedad mínima residual; 28,3 por ciento recibió trasplante de médula ósea y el 10 por ciento (6) presentó compromiso de líquido cefalorraquídeo. En la segunda citometría en pacientes con enfermedad mínima residual, 90,9 por ciento (20) expresaba CD45+. El 31,8 por ciento (7) de los pacientes con enfermedad mínima residual presentó recaída. Conclusión: La enfermedad mínima residual es una condición frecuente en pacientes con leucemias agudas que requiere seguimiento y constituye un factor pronóstico relevante(AU)
Introduction: The minimal residual disease is the permanence of residual leukemic cells at subclinical levels after remission of the disease. This condition increases the risk of relapse and mortality. Objective: To characterize the clinical and molecular factors of patients with acute leukemias and minimal residual disease detected by flow cytometry in a highly complex institution in the city of Medellín, Colombia during the years 2015 - 2017. Methodology: This is a retrospective descriptive observational study, which included patients with leukemia diagnosed by flow cytometry. A non-probabilistic sampling of consecutive cases was carried out. The information collected was entered into a database in Excel, and the analysis was carried out through the IBM SPSS Version 24 program, using absolute and relative frequencies, average and standard deviation or median and interquartile ranges, according to the nature of each variable and its distribution. Results: 60 patients were included in which male sex predominated with 63.3 percent (38). The most frequent diagnosis was lymphoid leukemia with 78.3 percent (47). Of the total patients included, 36.6 percent (22) were positive for minimal residual disease; 28.3 percent received a bone marrow transplant and 10 percent (6) had a cerebrospinal fluid compromise. In the second cytometry of the patients with minimal residual disease, 90.9 percent (20) expressed CD45 +. 31.8 percent (7) of the patients with minimal residual disease relapsed. Conclusion: Minimal residual disease is a frequent pathology in patients with acute leukemias that requires follow-up and constitutes a relevant prognostic factor(AU)
Assuntos
Humanos , Masculino , Feminino , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/prevenção & controle , Neoplasia Residual/diagnóstico , Citometria de Fluxo/métodos , Epidemiologia Descritiva , Estudos RetrospectivosRESUMO
Introducción: La identificación de políticas públicas y estrategias en salud bucal, así como lo relacionado con sus propósitos, acciones y limitaciones, es un paso importante en la acción intersectorial en salud para alcanzar equidad. Objetivo: Describir las características principales de los documentos relacionados con planes, políticas y estrategias en salud bucal en Latinoamérica y el Caribe. Métodos: Estudio exploratorio mediante el análisis documental de fuentes secundarias de información disponibles en las páginas web de los ministerios de salud de 23 países, y rastreo sistemático en el buscador Google, sin restricción espacio-temporal. Se realizó análisis de contenido cuantitativo y cualitativo. Resultados: Se analizaron 85 documentos. Los países con mayor número de documentos relacionados con el tema propuesto fueron Colombia (n = 14), México (n = 8) y Panamá (n = 7). Una buena parte centran su atención en poblaciones específicas; por ejemplo: gestantes, comunidades vulnerables, escolares, maestros, entre otras. Tienen como propósito la disminución de factores de riesgo para las principales enfermedades bucales, desde enfoques relacionados con los determinantes sociales. El enfoque de género es más tímido y centra su atención en necesidades especiales de las mujeres en embarazo, parto y posparto. Los objetivos de la mayoría de los documentos analizados consistían en una atención integral sobre el estado de salud bucodental, mediante acciones de educación, promoción y actividades clínicas a la población, según sus necesidades. Conclusiones: Se encontró una representación importante de países que tienen documentos relacionados con programas y planes nacionales o locales y con indicadores que reflejan su cumplimiento. También existen guías prácticas de actuación. Aunque en el diseño y construcción de los documentos intervienen profesionales, sobre todo de la estomatología, falta la participación de otras áreas del conocimiento que ayudarían a lograr una visión más amplia hacia la determinación social de la salud(AU)
Introduction: The identification of public policies and strategies in oral health, as well as its purposes, actions and limitations is an important step in intersectoral action in health to achieve equity. Objective: To describe the main characteristics of the documents related to oral health plans, policies and strategies in Latin America en the Caribbean. Methods: An exploratory study was conducted by means of documentary analysis of secondary sources of information available on the websites of the ministries of health of 23 countries, and systematic search in the Google, without spatio-temporal restriction. Quantitative and qualitative content analysis was performed. Results: 85 documents were analyzed. The countries with the highest number of documents related to the research topic were Colombia (n = 14), Mexico (n = 8) and Panama (n = 7). A good part is focused on specific populations, such as pregnant women, socially vulnerable communities, school children, teachers, among others. Their purpose is to reduce risk factors for the main oral diseases, making important advances in approaches related to social determinants. However, the gender approach is more timid by focusing attention on the oral health special needs of women in pregnancy, childbirth and postpartum. The main objectives of most of the documents analyzed consisted of an integral attention on the state of oral health, applying education, promotion and clinical activities to the population, according to their needs. Conclusions: An important representation of countries with documents related to national or local programs and plans were found and they have indicators that reflect their compliance. Also practical action guides were described. Although many professionals, especially in dentistry, intervene in the design and construction of documents, the participation of other areas of knowledge is lacking, what will help to achieve a broader vision towards the social determination of health(AU)
Assuntos
Humanos , Política Pública , Planos e Programas de Saúde , Saúde Bucal/tendências , Estratégias de Saúde , Odontologia em Saúde Pública/métodos , Ferramenta de Busca/métodos , América LatinaRESUMO
Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (SS,1R)-1-docecylsulfiny-5N,6O-oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (SS)-DS-ONJ in microglia. (SS)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR.
Assuntos
Anti-Inflamatórios/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Glicolipídeos/uso terapêutico , Sulfóxidos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Retinopatia Diabética/imunologia , Retinopatia Diabética/patologia , Gliose , Glicolipídeos/química , Glicolipídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação , Lipopolissacarídeos/efeitos adversos , Microglia/efeitos dos fármacos , Microglia/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Retina/efeitos dos fármacos , Retina/imunologia , Retina/patologia , Transdução de Sinais/efeitos dos fármacos , Sulfóxidos/química , Sulfóxidos/farmacologiaRESUMO
Objetivo: evaluar la percepción de los estudiantes sobre un modelo educativo basado en simulación, en una escuela de medicina privada ubicada en Medellín, Colombia, respecto a su capacidad para desempeñarse en escenarios clínicos reales. Materiales y métodos: estudio transversal. La muestra fueron estudiantes de medicina del IV al XIII período académico. Los datos se recolectaron en fuentes primarias, mediante el diseño y aplicación de un cuestionario. Resultados: la muestra incluyó 300 estudiantes durante sus prácticas clínicas y pasantías y la edad promedio fue de 21,9 años. El 68,3% (n = 205) de la muestra eran mujeres. Se evaluó el nivel de satisfacción con la experiencia de usar simulación clínica; el 65,3% (n = 196) describió la experiencia como satisfactoria, el 2% (n = 6) y el 23% (n = 69) como insatisfactoria y moderadamente satisfactoria respectivamente; los participantes restantes 9,7% (n = 29) describieron la experiencia como totalmente satisfactoria. En cuanto a la percepción de las competencias desarrolladas bajo el modelo educativo se destacan el razonamiento clínico, 98% (n = 294) y la toma de decisiones, 95% (n = 285). Conclusión: los estudiantes encuestados percibieron que la simulación facilita el aprendizaje al posibilitar el desarrollo de habilidades como el trabajo en equipo y la comunicación, lo que genera un alto grado de satisfacción en los estudiantes con respecto a su proceso de formación..(Au)
Objective: to assess perception of the students on a simulation-based educational model, in a private medical school located at the municipality of Medellín, Colombia, regarding with their ability to perform in real clinical scenarios. Materials and methods: a cross sectional study. Sample were medical students from IV to the XIII academic period. Data was collected from primary sources, through the design and application of a questionnaire. Results: the sample included were 300 students during their clinical practices and clerkship, the mean age was 21.9 years. 68.3% (205) of the sample were female. We assess the level of satisfaction with the experience of using clinical simulation; 65.3% (n=196) described the experience as satisfactory, 2% (n=6) and 23% (n=69) as unsatisfactory and moderately satisfactory respectively; remaining participants described the experience as full satisfactory. Regarding the perception of the competences developed under the simulation-based education model, the main ones were 98% (n=294) clinical reasoning and 95% (n=285) decision making. Conclusion: surveyed students perceived that simulation facilitates learning by making possible the development of skills such as teamwork and communication, which generates a high degree of satisfaction in students regarding their training process..(Au)
RESUMO
Host shifts can drastically change the selective pressures that animals experience from their environment. Drosophila sechellia is a species restricted to the Seychelles islands, where it specializes on the fruit Morinda citrifolia (noni). This fruit is known to be toxic to closely related Drosophila species, including D. melanogaster and D. simulans, releasing D. sechellia from interspecific competition when breeding on this substrate. Previously, we showed that larvae of D. sechellia are unable to mount an effective immunological response against wasp attack, while larvae of closely-related species can defend themselves from parasitoid attack by melanotic encapsulation. We hypothesized that this inability constitutes a trait loss due to a reduced risk of parasitoid attack in noni. Here we present a lab experiment and field survey aimed to test the hypothesis that specialization on noni has released D. sechellia from the antagonistic interaction with its larval parasitoids. Our results from the lab experiment suggest that noni may be harmful to parasitoid wasps. Our results from the field survey indicate that D. sechellia was found in ripe noni, whereas another Drosophila species, D. malerkotliana, was present in unripe and overripe stages. Parasitic wasps of the species Leptopilina boulardi emerged from overripe noni, where D. malerkotliana was the most abundant host, but not from ripe noni. These results indicate that the specialization of D. sechellia on noni has indeed drastically altered its ecological interactions, leading to a relaxation in the selection pressure to maintain parasitoid resistance.