Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis

Background: the abnormal epithelial-mesenchymal restorative capacity in idiopathic pulmonary fibrosis (IPF) has been recently associated with an accelerated aging process as a key point for the altered wound healing. The advanced glycation end-products (AGEs) are the consequence of non-enzymatic reactions between lipid and protein with several oxidants in the aging process. The receptor for AGEs (RAGEs) has been implicated in the lung fibrotic process and the alveolar homeostasis. However, this AGE-RAGE aging pathway has been under-explored in IPF. Methods: lung samples from 16 IPF and 9 control patients were obtained through surgical lung biopsy. Differences in AGEs and RAGE expression between both groups were evaluated by RT-PCR, Western blot and immunohistochemistry. The effect of AGEs on cell viability of primary lung fibrotic fibroblasts and alveolar epithelial cells was assessed. Cell transformation of fibrotic fibroblasts cultured into glycated matrices was evaluated in different experimental conditions. Results: our study demonstrates an increase of AGEs together with a decrease of RAGEs in IPF lungs, compared with control samples. Two specific AGEs involved in aging, pentosidine and Nε-Carboxymethyl lysine, were significantly increased in IPF samples. The immunohistochemistry identified higher staining of AGEs related to extracellular matrix (ECM) proteins and the apical surface of the alveolar epithelial cells (AECs) surrounding fibroblast foci in fibrotic lungs. On the other hand, RAGE location was present at the cell membrane of AECs in control lungs, while it was almost missing in pulmonary fibrotic tissue. In addition, in vitro cultures showed that the effect of AGEs on cell viability was different for AECs and fibrotic fibroblasts. AGEs decreased cell viability in AECs, even at low concentration, while fibroblast viability was less affected. Furthermore, fibroblast to myofibroblast transformation could be enhanced by ECM glycation. Conclusions: all of these findings suggest a possible role of the increased ratio AGEs-RAGEs in IPF, which could be a relevant accelerating aging tissue reaction in the abnormal wound healing of the lung fibrotic process

Frequency and Associated Factors of Suicidal Ideation in Patients with Chronic Obstructive Pulmonary Disease

COPD; Depression; SuicideEPOC; Depresión; SuicidioMPOC; Depressió; SuïcidiWe aimed to examine the prevalence of suicidal ideation in patients with chronic obstructive pulmonary disease (COPD) and the association between demographic and clinical variables and the occurrence of suicidal thoughts. This was a cross-sectional study. Sociodemographic and clinical data were recorded, and questionnaires were used to assess depressive symptoms (Beck Depression Inventory), comorbidities (Charlson Index), cognitive performance (Mini Mental State Examination), and quality of life (EuroQoL-5 dimensions and CAT). Specific questions about suicide-related behavior were included. Multivariate logistic regression analysis identified the significant factors associated with previous suicidal ideation and suicide attempts. The analysis included 1190 subjects. The prevalence of suicidal ideation and suicide attempts were 12.1% and 2.5%, respectively. Severely depressed patients had the highest prevalence of suicide-related behavior. The adjusted logistic model identified factors significantly associated with suicidal ideation: sex (odds ratio (OR) for women vs. men = 2.722 (95% confidence interval (CI) = 1.771–4.183)), depression score (OR = 1.163 (95% IC = 1.127–1.200)), and Charlson Index (OR 1.228 (95% IC 1.082–1.394)). Suicidal ideation is common in COPD patients, especially in women. While addressing suicidal ideation and suicide prevention, clinicians should first consider the management of depressive symptomatology and the improvement of coping strategies.The DeprEPOC study was funded by an unrestricted grant from Grupo Ferrer (Barcelona, Spain)

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes. Methods: All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. Results: In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6 +/- 1.5% vs. 14.2 +/- 1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for % IA between the 2 groups (37.3 +/- 2.2% vs. 29.3 +/- 2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the % IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008). Conclusions: Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population

Ecommerce white book colombia a guide adapted to the needs of colombian Msmes

Este documento presenta una indagación que da cuenta del esfuerzo investigativo para compilar un libro con las mejores prácticas e información de contexto del comercio electrónico en Colombia orientado a facilitar a las micro, pequeñas y medianas empresas la implementación y desarrollo de este canal de comercialización. Esta iniciativa nace a partir de la necesidad del Ministerio de Tecnologías de la Información y las Comunicaciones – MINTIC, de contar con herramientas que apoyen el robustecimiento del aparato productivo colombiano y de minimizar la brecha tecnológica existente entre estas empresas. Para dar respuesta a dicho objetivo, se desarrolló un estudio de tipo cualitativo descriptivo donde se destaca la revisión bibliográfica y las entrevistas a profundidad. De acuerdo a lo anterior, este trabajo de grado abordará los aspectos principales para el desarrollo del proyecto, desarrollando el problema de investigación desde sus antecedentes y planteando los objetivos y justificaciones pertinentes que permitan establecer claramente los lineamientos claros para su desarrollo. Cabe mencionar que, a partir de la literatura consultada y el trabajo de campo desarrollado mediante la inclusión de entrevistas a profundidad con expertos sobre comercio electrónico, se establecerán herramientas para el desarrollo de un comercio electrónico.MINTICThis document presents an inquiry that accounts for the research effort to compile a book with the best practices and contextual information on electronic commerce in Colombia aimed at facilitating the implementation and development of this marketing channel for micro, small and medium-sized enterprises. This initiative was born from the need of the Ministry of Information Technologies and Communications - MINTIC, to have tools that support the strengthening of the Colombian productive apparatus and to minimize the existing technological gap between these companies. To respond to this objective, a descriptive qualitative study was developed where the bibliographic review and in-depth interviews stand out. According to the above, this degree work will address the main aspects for the development of the project, developing the research problem from its antecedents and proposing the pertinent objectives and justifications that allow to clearly establish the clear guidelines for its development. It is worth mentioning that, based on the literature consulted and the field work developed by including in-depth interviews with experts on electronic commerce, tools will be established for the development of electronic commerce.Magíster en Gerencia de Sistemas de Información y Proyectos TecnológicosMaestrí

Dificultades socioafectivas de los niños y las niñas del hogar infantil Travesuras

Este trabajo de investigación da cuenta del proyecto realizado en el Hogar Infantil Travesuras, grado pre-jardín A; donde se busco fortalecer el quehacer pedagógico de los docentes a cargo de la educación de los infantes. También se mostró como desde el campo educativo se puede intervenir asertivamente en diferentes problemáticas de tipo comportamental y de socialización, no solo para favorecer los aprendizajes de los niños y todo lo que estos conllevan, sino también para generar herramientas que permitan abordar dichas situaciones por medio del desarrollo de estrategias didácticas enfocadas en la dimensión socio-afectiva

Dificultades socioafectivas de los niños y las niñas del hogar infantil Travesuras

Este trabajo de investigación da cuenta del proyecto realizado en el Hogar Infantil Travesuras, grado pre-jardín A; donde se busco fortalecer el quehacer pedagógico de los docentes a cargo de la educación de los infantes. También se mostró como desde el campo educativo se puede intervenir asertivamente en diferentes problemáticas de tipo comportamental y de socialización, no solo para favorecer los aprendizajes de los niños y todo lo que estos conllevan, sino también para generar herramientas que permitan abordar dichas situaciones por medio del desarrollo de estrategias didácticas enfocadas en la dimensión socio-afectiva

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1

Background Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. Methods ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. Results A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. Conclusions The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing

Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices

Background: There is growing interest in the development of cell culture assays that enable the rigidity of the extracellular matrix to be increased. A promising approach is based on three-dimensional collagen type I matrices that are stiffened by cross-linking through non-enzymatic glycation with reducing sugars. Methods: The present study evaluated the biomechanical changes in the non-enzymatically glycated type I collagen matrices, including collagen organization, the advanced glycation end products formation and stiffness achievement. Gels were glycated with ribose at different concentrations (0, 5, 15, 30 and 240 mM). The viability and the phenotypic changes of primary human lung fibroblasts cultured within the non-enzymatically glycated gels were also evaluated along three consecutive weeks. Statistical tests used for data analyze were MannWhitney U, Kruskal Wallis, Student's t-test, two-way ANOVA, multivariate ANOVA, linear regression test and mixed linear model. Results: Our findings indicated that the process of collagen glycation increases the stiffness of the matrices and generates advanced glycation end products in a ribose concentration-dependent manner. Furthermore, we identified optimal ribose concentrations and media conditions for cell viability and growth within the glycated matrices. The microenvironment of this collagen based three-dimensional culture induces α-smooth muscle actin and tenascin-C fibroblast protein expression. Finally, a progressive contractile phenotype cell differentiation was associated with the contraction of these gels. Conclusions: The use of non-enzymatic glycation with a low ribose concentration may provide a suitable model with a mechanic and oxidative modified environment with cell s embedded in it, which allowed cell proliferation and induced fibroblast phenotypic changes. Such culture model could be appropriate for investigations of the behavior and phenotypic changes in cells that occur during lung fibrosis as well as for testing different antifibrotic therapies in vitro

Cognitive status among patients with chronic obstructive pulmonary disease

We investigated the association between cognitive impairment and chronic obstructive pulmonary disease (COPD), taking into account demographic and clinical variables evaluated during routine practice. We performed a post hoc analysis of a cross-sectional study that included subjects with stable COPD. Sociodemographic and clinical information was recorded using the Body mass index, airflow Obstruction, Dyspnea and Exacerbations index and the Charlson comorbidity index. Cognitive performance was studied by the mini-mental state examination, with a score less than 27 indicating clinical impairment. Depressive symptoms, physical activity, and quality of life (EuroQoL-5 dimensions and COPD Assessment Test) were also evaluated. The analysis included 940 subjects. The prevalence of cognitive impairment was 39.4%. Multivariate logistic regression models revealed that cognitive impairment was associated with educational level (odds ratio [OR] =0.096, 95% confidence interval [CI] =0.011-0.447) and poorer quality of life measured by the EuroQoL-5 dimensions social tariff (OR =0.967, 95% CI =0.950-0.983). When questionnaires were not included in the analysis, cognitive impairment was associated with educational level (OR =0.063, 95% CI =0.010-0.934), number of exacerbations (OR =11.070, 95% CI =1.450-84.534), Body mass index, airflow Obstruction, Dyspnea and Exacerbations index score (OR =1.261, 95% CI =1.049-1.515), and the Charlson comorbidity index (OR =1.412, 95% CI =1.118-1.783). Cognitive impairment is common in COPD and is associated with low educational level, higher disease severity, and increased comorbidity. This could have therapeutic implications for this population

Eccentric Dipole Evolution during the Last Reversal, Last Excursions, and Holocene Anomalies. Interpretation Using a 360-Dipole Ring Model

The eccentric dipole (ED) is the next approach of the geomagnetic field after the generally used geocentric dipole. Here, we analyzed the evolution of the ED during extreme events, such as the Matuyama-Brunhes polarity transition (~780 ka), the Laschamp (~41 ka) and Mono Lake (~34 ka) excursions, and during the time of two anomalous features of the geomagnetic field observed during the Holocene: the Levantine Iron Age Anomaly (LIAA, ~1000 BC) and the South Atlantic Anomaly (SAA, analyzed from ~700 AD to present day). The analysis was carried out using the paleoreconstructions that cover the time of the mentioned events (IMMAB4, IMOLEe, LSMOD.2, SHAWQ-Iron Age, and SHAWQ2k). We found that the ED moves around the meridian plane of 0–180◦ during the reversal and the excursions; it moves towards the region of the LIAA; and it moves away from the SAA. To investigate what information can be extracted from its evolution, we designed a simple model based on 360-point dipoles evenly distributed in a ring close to the inner core boundary that can be reversed and their magnitude changed. We tried to reproduce with our simple model the observed evolution of the ED, and the total field energy at the Earth’s surface. We observed that the modeled ED moves away from the region where we set the dipoles to reverse. If we consider that the ring dipoles could be related to convective columns in the outer core of the Earth, our simple model would indicate the potential of the displacement of the ED to give information about the regions in the outer core where changes start for polarity transitions and for the generation of important anomalies of the geomagnetic field. According to our simple model, the regions in which the most important events of the Holocene occur, or in which the last polarity reversal or excursion begin, are related to the regions of the Core Mantle Boundary (CMB), where the heat flux is low