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1.
Reumatol. clín. (Barc.) ; 15(2): 102-108, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: ibc-ET1-3371

RESUMO

Objectives: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). Methods: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. Results: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. Conclusions: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal


Objetivos: Describir la prevalencia de comorbilidades en pacientes con AR en España y discutir sobre su manejo en la clínica diaria utilizando los datos de la cohorte española del estudio internacional COMORA. Métodos: Subanálisis nacional del estudio COMORA en el que se analizaron las características demográficas y clínicas de 200 pacientes con AR (1987 ACR) y las prácticas rutinarias para el cribado y la prevención de eventos cardiovasculares (CV), gastrointestinales y pulmonares, infecciones, cáncer, osteoporosis y depresión. Resultados: Los pacientes tenían una edad media de 58 años, una duración media de la enfermedad de 10 años, un DAS28 de 3,3 y el 25% estaba en remisión (DAS28 <2,6). El 22% de los pacientes presentaba al menos una comorbilidad, principalmente depresión (27%) y obesidad (26%). El 5% tenía historia de infarto de miocardio, el 1% de ictus y el 6% de tumor sólido. Una puntuación de Framingham >20% (51%), tener hipercolesterolemia (46%), hipertensión (41%) y fumar (25%) fueron los factores de riesgo CV más comunes. En relación con el cáncer de próstata, colon y piel, solo el 9, 10 y el 18% de los pacientes, respectivamente, estaban óptimamente controlados. Las infecciones tampoco se manejaban de forma óptima, con solo el 7 y el 17% de los pacientes vacunados contra la influenza y neumococo, respectivamente, al igual que la osteoporosis, con el 47% suplementados con la vitamina D y el 56% con una densitometría realizada. Conclusiones: En España, la prevalencia de comorbilidades y factores de riesgo CV en pacientes con AR establecida y avanzada es relativamente alta, y su manejo en la clínica diaria continúa siendo subóptimo

2.
J Rheumatol ; 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988123

RESUMO

OBJECTIVE: To describe the incidence of bacteremia in a large multicentric cohort of patients with systemic lupus erythematosus (SLE) and their clinical characteristics and to identify risk factors. METHODS: All bacteremic episodes from the Spanish RELESSER registry were included. Clinical and laboratory characteristics concerning bacteremia and SLE status, as well as comorbidities at the time of infection, were retrospectively collected. A comparison with sex- and age-matched SLE controls without bacteremia was made. A logistic regression was conducted. RESULTS: The study included 114 episodes of bacteremia in 83 patients. The incidence rate was 2.7/1000 patient-years. At the time of bacteremia, the median age was 40.5 (range: 8-90) years, and 88.6% of patients were female. The Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index was 4 [interquartile range (IQR) 8]; 41% had an SLE flare (66% severe); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was 3 (IQR 4). A comorbidity was recorded in 64% of cases. At the time of bacteremia, 88.6% received corticosteroids (68.6% > 10 mg/day) and 57% immunosuppressors. Gram-negative bacilli, most frequently Escherichia coli (29.8%), caused 52.6% of the episodes. The bacteremia-related mortality was 14% and bacteremia was recurrent in 27.2% of cases. A dose-response relationship was found between corticosteroids and bacteremia risk. In the multivariate analysis, these factors were associated with bacteremia: elevated creatinine (OR 1.31, 95% CI 1.01-1.70; p = 0.045), diabetes (OR 6.01, 95% CI 2.26-15.95; p < 0.001), cancer (OR 5.32, 95% CI 2.23-12.70; p < 0.001), immunosuppressors (OR 6.35, 95% CI 3.42-11.77; p < 0.001), and damage (OR 1.65, 95% CI 1.31-2.09; p < 0.001). CONCLUSION: Bacteremia occurred mostly in patients with active SLE and was frequently associated with severe flares and corticosteroid use. Recurrence and mortality were high. Immunosuppressors, comorbidities, and disease-related damage were associated with bacteremia.

3.
PLoS One ; 14(3): e0212200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893307

RESUMO

High throughput phenotyping technologies are lagging behind modern marker technology impairing the use of secondary traits to increase genetic gains in plant breeding. We aimed to assess whether the combined use of hyperspectral data with modern marker technology could be used to improve across location pre-harvest yield predictions using different statistical models. A maize bi-parental doubled haploid (DH) population derived from F1, which consisted of 97 lines was evaluated in testcross combination under heat stress as well as combined heat and drought stress during the 2014 and 2016 summer season in Ciudad Obregon, Sonora, Mexico (27°20" N, 109°54" W, 38 m asl). Full hyperspectral data, indicative of crop physiological processes at the canopy level, was repeatedly measured throughout the grain filling period and related to grain yield. Partial least squares regression (PLSR), random forest (RF), ridge regression (RR) and Bayesian ridge regression (BayesB) were used to assess prediction accuracies on grain yield within (two-fold cross-validation) and across environments (leave-one-environment-out-cross-validation) using molecular markers (M), hyperspectral data (H) and the combination of both (HM). Highest prediction accuracy for grain yield averaged across within and across location predictions (rGP) were obtained for BayesB followed by RR, RF and PLSR. The combined use of hyperspectral and molecular marker data as input factor on average had higher predictions for grain yield than hyperspectral data or molecular marker data alone. The highest prediction accuracy for grain yield across environments was measured for BayesB when molecular marker data and hyperspectral data were used as input factors, while the highest within environment prediction was obtained when BayesB was used in combination with hyperspectral data. It is discussed how the combined use of hyperspectral data with molecular marker technology could be used to introduce physiological genomic estimated breeding values (PGEBV) as a pre-harvest decision support tool to select genetically superior lines.

4.
G3 (Bethesda) ; 9(4): 1231-1247, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30796086

RESUMO

Hyperspectral reflectance phenotyping and genomic selection are two emerging technologies that have the potential to increase plant breeding efficiency by improving prediction accuracy for grain yield. Hyperspectral cameras quantify canopy reflectance across a wide range of wavelengths that are associated with numerous biophysical and biochemical processes in plants. Genomic selection models utilize genome-wide marker or pedigree information to predict the genetic values of breeding lines. In this study, we propose a multi-kernel GBLUP approach to genomic selection that uses genomic marker-, pedigree-, and hyperspectral reflectance-derived relationship matrices to model the genetic main effects and genotype × environment (G × E) interactions across environments within a bread wheat (Triticum aestivum L.) breeding program. We utilized an airplane equipped with a hyperspectral camera to phenotype five differentially managed treatments of the yield trials conducted by the Bread Wheat Improvement Program of the International Maize and Wheat Improvement Center (CIMMYT) at Ciudad Obregón, México over four breeding cycles. We observed that single-kernel models using hyperspectral reflectance-derived relationship matrices performed similarly or superior to marker- and pedigree-based genomic selection models when predicting within and across environments. Multi-kernel models combining marker/pedigree information with hyperspectral reflectance phentoypes had the highest prediction accuracies; however, improvements in accuracy over marker- and pedigree-based models were marginal when correcting for days to heading. Our results demonstrate the potential of using hyperspectral imaging to predict grain yield within a multi-environment context and also support further studies on the integration of hyperspectral reflectance phenotyping into breeding programs.


Assuntos
Melhoramento Vegetal/métodos , Triticum/genética , Interação Gene-Ambiente , Marcadores Genéticos , Genoma de Planta , Genótipo , México , Fenótipo , Seleção Genética , Triticum/crescimento & desenvolvimento
5.
J Child Sex Abus ; 28(4): 417-434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30762481

RESUMO

Child serving professionals need increased understanding of the identification and therapeutic needs of child victims of commercial sexual exploitation. This study evaluated the effectiveness of a training program aimed to increase awareness of commercial sexual exploitation of children (CSEC) among professionals likely to encounter victims in their work. Professionals' (N = 227) knowledge level was examined prior to the training, immediately thereafter, and in a 6-12 month follow-up. Despite professional position or years of experience, participants had similar levels of CSEC knowledge before the training and all showed a significant improvement in their knowledge after the training. However, follow-up testing on a smaller subsample demonstrated that knowledge gains were not maintained. The analysis of the participants' responses to how their behavior would change subsequent to the training revealed important themes including: (1) greater ability to identify/assess or recognize CSEC victims, (2) greater understanding and knowledge of CSEC, (3) increased ability to communicate, interact, and engage with CSEC victims, and (4) heightened desire to educate others and raise awareness about CSEC. Results also indicated that participants were very satisfied with the training and found it highly relevant to their work.


Assuntos
Abuso Sexual na Infância , Vítimas de Crime , Educação Continuada , Conhecimentos, Atitudes e Prática em Saúde , Tráfico de Pessoas , Avaliação de Programas e Projetos de Saúde , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino
6.
Angew Chem Int Ed Engl ; 58(14): 4581-4586, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30720233

RESUMO

The synthesis and aqueous self-assembly of a new class of amphiphilic aliphatic polyesters are presented. These AB block polyesters comprise polycaprolactone (hydrophobe) and an alternating polyester from succinic acid and an ether-substituted epoxide (hydrophile). They self-assemble into biodegradable polymersomes capable of entering cells. Their degradation products are bioactive, giving rise to differentiated cellular responses inducing stromal cell proliferation and macrophage apoptosis. Both effects emerge only when the copolymers enter cells as polymersomes and their magnitudes are size dependent.

7.
Chem Asian J ; 14(4): 509-526, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30716209

RESUMO

Zinc is a biocompatible element that exists as the second most abundant transition metal ion and an indispensable trace element in the human body. Compared to traditional metal-organic complexes systems, d10 metal ZnII complexes not only exhibit a large Stokes shift and good photon stability but also possess strong emission and low cytotoxicity with a relatively small molecular weight. The use of ZnII complexes has emerged in the last decade as a versatile and convenient tool for numerous biological applications, including bioimaging, molecular and protein recognition, as well as photodynamic therapy. Herein, we review recent developments involving ZnII metal complexes applied as specific subcellular compartment imaging probes and their correlated utilizations.


Assuntos
Complexos de Coordenação/farmacologia , Corantes Fluorescentes/farmacologia , Zinco/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Complexos de Coordenação/química , Corantes Fluorescentes/química , Humanos , Membranas Intracelulares/metabolismo , Microscopia Confocal/métodos , Espectrometria de Fluorescência/métodos
8.
Lab Invest ; 99(3): 421-437, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30664710

RESUMO

Systemic inflammatory diseases enhance circulating oxidative stress levels, which results in the oxidation of circulating high-density lipoprotein (oxHDL). Endothelial cell function can be negatively impacted by oxHDL, but the underlying mechanisms for this remain unclear. Some reports indicate that the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is also a receptor for oxHDL. However, it is unknown if oxHDL induces increased LOX-1 expression at the plasma membrane, as an event that supports endothelial dysfunction. Therefore, the aims of this study were to determine if oxHDL induces plasma-membrane level changes in LOX-1 and, if so, to describe the underlying mechanisms in endothelial cells. Our results demonstrate that the incubation of arterial or vein endothelial cells with oxHDL (and not HDL) induces the increase of LOX-1 expression at the plasma membrane; effect prevented by LOX-1 inhibition. Importantly, same results were observed in endothelial cells from oxHDL-treated rats. Furthermore, the observed oxHDL-induced LOX-1 expression is abolished by the down-regulation of NOX-2 expression with siRNA (and no others NOX isoforms), by the pharmacological inhibition of NAD(P)H oxidase (with DPI or apocynin) or by the inhibition of NF-κB transcription factor. Coherently, LOX-1 expression is augmented by the incubation of endothelial cells with H2O2 or GSSG even in absence of oxHDL, indicating that the NOX-2/ROS/ NF-κB axis is involved. Interestingly, oxHDL incubation also increases TNF-α expression, cytokine that induces LOX-1 expression. Thus, our results suggest a positive feedback mechanism for LOX-1 receptor during inflammatory condition where an oxidative burst will generate oxHDL from native HDL, activating LOX-1 receptor which in turn will increase the expression of NOX-2, TNF-α and LOX-1 receptor at the plasma membrane. In conclusion, oxHDL-induced translocation of LOX-1 to the plasma membrane could constitute an induction mechanism of endothelial dysfunction in systemic inflammatory diseases.


Assuntos
Células Endoteliais/metabolismo , Lipoproteínas HDL/metabolismo , Receptores Depuradores Classe E/metabolismo , Animais , Membrana Celular/metabolismo , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/metabolismo , Masculino , NADPH Oxidase 2/metabolismo , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
9.
Immunity ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30446388

RESUMO

Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. CXCL1 was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling. Conversely, neutrophils were the main producers of CXCL2, and this chemokine was critical for correct breaching of endothelial junctions. This pro-migratory activity of CXCL2 depended on the atypical chemokine receptor 1 (ACKR1), which is enriched within endothelial junctions. Transmigrating neutrophils promoted a self-guided migration response through EC junctions, creating a junctional chemokine "depot" in the form of ACKR1-presented CXCL2 that enabled efficient unidirectional luminal-to-abluminal migration. Thus, CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources.

10.
Biomaterials ; 192: 26-50, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30419394

RESUMO

Life and biological units are the result of the supramolecular arrangement of many different types of molecules, all of them combined with exquisite precision to achieve specific functions. Taking inspiration from the design principles of nature allows engineering more efficient and compatible biomaterials. Indeed, bionic (from bion-, unit of life and -ic, like) materials have gained increasing attention in the last decades due to their ability to mimic some of the characteristics of nature systems, such as dynamism, selectivity, or signalling. However, there are still many challenges when it comes to their interaction with the human body, which hinder their further clinical development. Here we review some of the recent progress in the field of molecular bionics with the final aim of providing with design rules to ensure their stability in biological media as well as to engineer novel functionalities which enable navigating the human body.

11.
Theor Appl Genet ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341493

RESUMO

Genomic selection and high-throughput phenotyping (HTP) are promising tools to accelerate breeding gains for high-yielding and climate-resilient wheat varieties. Hence, our objective was to evaluate them for predicting grain yield (GY) in drought-stressed (DS) and late-sown heat-stressed (HS) environments of the International maize and wheat improvement center's elite yield trial nurseries. We observed that the average genomic prediction accuracies using fivefold cross-validations were 0.50 and 0.51 in the DS and HS environments, respectively. However, when a different nursery/year was used to predict another nursery/year, the average genomic prediction accuracies in the DS and HS environments decreased to 0.18 and 0.23, respectively. While genomic predictions clearly outperformed pedigree-based predictions across nurseries, they were similar to pedigree-based predictions within nurseries due to small family sizes. In populations with some full-sibs in the training population, the genomic and pedigree-based prediction accuracies were on average 0.27 and 0.35 higher than the accuracies in populations with only one progeny per cross, indicating the importance of genetic relatedness between the training and validation populations for good predictions. We also evaluated the item-based collaborative filtering approach for multivariate prediction of GY using the green normalized difference vegetation index from HTP. This approach proved to be the best strategy for across-nursery predictions, with average accuracies of 0.56 and 0.62 in the DS and HS environments, respectively. We conclude that GY is a challenging trait for across-year predictions, but GS and HTP can be integrated in increasing the size of populations screened and evaluating unphenotyped large nurseries for stress-resilience within years.

12.
Int J Obes (Lond) ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262813

RESUMO

BACKGROUND: The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown. OBJECTIVE: To assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers. DESIGN: Randomized, parallel, double-blind, placebo-controlled trial with abdominally obese individuals. Participants (n = 135) consumed 1 capsule/day containing 1010 colony forming unit (CFU) of Ba8145, 1010 CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months. RESULTS: Ba8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003). CONCLUSIONS: In abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.

13.
iScience ; 7: 132-144, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30267675

RESUMO

Polymersomes are vesicles formed by the self-assembly of amphiphilic copolymers in water. They represent one of the most promising alternatives of natural vesicles as they add new possibilities in the amphiphiles' molecular engineering of aqueous compartments. Here we report the design of polymersomes using a bottom-up approach wherein self-assembly of amphiphilic copolymers poly(2-(methacryloyloxy) ethyl phosphorylcholine)-poly(2-(diisopropylamino) ethyl methacrylate) (PMPC-PDPA) into membranes is tuned using pH and temperature. We report evolution from disk micelles, to vesicles, to high-genus vesicles (vesicles with many holes), where each passage is controlled by pH switch or temperature. We show that the process can be rationalized, adapting membrane physics theories to disclose scaling principles that allow the estimation of minimal radius of vesiculation as well as chain entanglement and coupling. This approach allows us to generate nanoscale vesicles with genus from 0 to 70, which have been very elusive and difficult to control so far.

14.
Chemphyschem ; 19(16): 1987-1989, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-29763524

RESUMO

Polymeric vesicles, also called polymersomes, are highly efficient biomimetic systems. They can generate compartmentalized volumes at the nanoscale supported by synthetic amphiphilic membranes that closely mimic their biological counterparts. Membrane permeability and the ability to separate extreme pH gradients is a crucial condition a successful biomimetic system must meet. We show that polymersomes formed by non-ionic polybutadiene-b-polyethylene oxide (PBd-b-PEO) amphiphilic block copolymers engineer robust and stable membranes that are able to sustain pH gradients of 10 for a minimum of eight days. The cells' endo-lysomal compartments separate gradients between three and one, while we generated a pH gradient of threefold as great. This feature clearly is of great importance for applications as nanoreactors and drug-delivery systems where separating different aqueous volumes at the nanoscale level is an essential requirement.

15.
Plant Methods ; 13: 62, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769997

RESUMO

BACKGROUND: Modern agriculture uses hyperspectral cameras that provide hundreds of reflectance data at discrete narrow bands in many environments. These bands often cover the whole visible light spectrum and part of the infrared and ultraviolet light spectra. With the bands, vegetation indices are constructed for predicting agronomically important traits such as grain yield and biomass. However, since vegetation indices only use some wavelengths (referred to as bands), we propose using all bands simultaneously as predictor variables for the primary trait grain yield; results of several multi-environment maize (Aguate et al. in Crop Sci 57(5):1-8, 2017) and wheat (Montesinos-López et al. in Plant Methods 13(4):1-23, 2017) breeding trials indicated that using all bands produced better prediction accuracy than vegetation indices. However, until now, these prediction models have not accounted for the effects of genotype × environment (G × E) and band × environment (B × E) interactions incorporating genomic or pedigree information. RESULTS: In this study, we propose Bayesian functional regression models that take into account all available bands, genomic or pedigree information, the main effects of lines and environments, as well as G × E and B × E interaction effects. The data set used is comprised of 976 wheat lines evaluated for grain yield in three environments (Drought, Irrigated and Reduced Irrigation). The reflectance data were measured in 250 discrete narrow bands ranging from 392 to 851 nm (nm). The proposed Bayesian functional regression models were implemented using two types of basis: B-splines and Fourier. Results of the proposed Bayesian functional regression models, including all the wavelengths for predicting grain yield, were compared with results from conventional models with and without bands. CONCLUSIONS: We observed that the models with B × E interaction terms were the most accurate models, whereas the functional regression models (with B-splines and Fourier basis) and the conventional models performed similarly in terms of prediction accuracy. However, the functional regression models are more parsimonious and computationally more efficient because the number of beta coefficients to be estimated is 21 (number of basis), rather than estimating the 250 regression coefficients for all bands. In this study adding pedigree or genomic information did not increase prediction accuracy.

16.
Sci Adv ; 3(8): e1700362, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28782037

RESUMO

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.

17.
Reumatol Clin ; 2017 Jul 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28711461

RESUMO

OBJECTIVES: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.

18.
Lab Invest ; 97(9): 1033-1046, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28737766

RESUMO

During systemic inflammatory pathologies, mediators of inflammation circulate in the bloodstream and interact with endothelial cells (ECs), resulting in endothelial dysfunction that maintains and enhances the pathological condition. Inflammatory mediators change the protein expression profile of ECs, which become activated fibroblasts via endothelial-to-mesenchymal transition. This process is characterized by downregulated endothelial proteins and strongly upregulated fibrotic-specific genes and extracellular matrix-forming proteins. The main inductor of endothelial fibrosis is transforming growth factor-ß1 (TGF-ß1), which acts through the TGF-ß1/activin receptor-like kinase 5 (ALK5)/Smads intracellular signaling pathway. The signal transducer and activator of transcription 3 (STAT3) is also involved in fibrosis in several tissues (e.g. heart and vascular system), where STAT3 signaling decreases TGF-ß1-induced responses by directly interacting with Smad proteins, suggesting that decreased STAT3 could induce TGF-ß1-mediated fibrosis. However, it is unknown if suppressed STAT3 expression induces EC fibrosis through a mechanism involving the TGF-ß signaling pathway. The present study evaluated the fibrotic actions of STAT3 suppression in ECs and investigated TGF-ß1/ALK5/Smad4 signaling pathway participation. Suppressed STAT3 expression stimulated fibrotic conversion in ECs, as mediated by protein expression reprograming that decreased endothelial marker expression and increased fibrotic and extracellular matrix protein levels. The potential mechanism underlying these changes was dependent on TGF-ß1 secretion, the ALK5 activation pathway, and Smad4 translocation into the nucleus. We conclude that suppressed STAT3 expression converts ECs into activated fibroblasts via TGF-ß1/ALK5/Smad4 signaling pathway involvement.


Assuntos
Células Endoteliais/metabolismo , Fibrose/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Células Cultivadas , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais
19.
Front Physiol ; 8: 321, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28596735

RESUMO

The high mortality of cephalopod early stages is the main bottleneck to grow them from paralarvae to adults in culture conditions, probably because the inadequacy of the diet that results in malnutrition. Since visual analysis of digestive tract contents of paralarvae provides little evidence of diet composition, the use of molecular tools, particularly next generation sequencing (NGS) platforms, offers an alternative to understand prey preferences and nutrient requirements of wild paralarvae. In this work, we aimed to determine the diet of paralarvae of the loliginid squid Alloteuthis media and to enhance the knowledge of the diet of recently hatched Octopus vulgaris paralarvae collected in different areas and seasons in an upwelling area (NW Spain). DNA from the dissected digestive glands of 32 A. media and 64 O. vulgaris paralarvae was amplified with universal primers for the mitochondrial gene COI, and specific primers targeting the mitochondrial gene 16S gene of arthropods and the mitochondrial gene 16S of Chordata. Following high-throughput DNA sequencing with the MiSeq run (Illumina), up to 4,124,464 reads were obtained and 234,090 reads of prey were successfully identified in 96.87 and 81.25% of octopus and squid paralarvae, respectively. Overall, we identified 122 Molecular Taxonomic Units (MOTUs) belonging to several taxa of decapods, copepods, euphausiids, amphipods, echinoderms, molluscs, and hydroids. Redundancy analysis (RDA) showed seasonal and spatial variability in the diet of O. vulgaris and spatial variability in A. media diet. General Additive Models (GAM) of the most frequently detected prey families of O. vulgaris revealed seasonal variability of the presence of copepods (family Paracalanidae) and ophiuroids (family Euryalidae), spatial variability in presence of crabs (family Pilumnidae) and preference in small individual octopus paralarvae for cladocerans (family Sididae) and ophiuroids. No statistically significant variation in the occurrences of the most frequently identified families was revealed in A. media. Overall, these results provide new clues about dietary preferences of wild cephalopod paralarvae, thus opening up new scenarios for research on trophic ecology and digestive physiology under controlled conditions.

20.
Plant Methods ; 13: 4, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28053649

RESUMO

BACKGROUND: Modern agriculture uses hyperspectral cameras to obtain hundreds of reflectance data measured at discrete narrow bands to cover the whole visible light spectrum and part of the infrared and ultraviolet light spectra, depending on the camera. This information is used to construct vegetation indices (VI) (e.g., green normalized difference vegetation index or GNDVI, simple ratio or SRa, etc.) which are used for the prediction of primary traits (e.g., biomass). However, these indices only use some bands and are cultivar-specific; therefore they lose considerable information and are not robust for all cultivars. RESULTS: This study proposes models that use all available bands as predictors to increase prediction accuracy; we compared these approaches with eight conventional vegetation indexes (VIs) constructed using only some bands. The data set we used comes from CIMMYT's global wheat program and comprises 1170 genotypes evaluated for grain yield (ton/ha) in five environments (Drought, Irrigated, EarlyHeat, Melgas and Reduced Irrigated); the reflectance data were measured in 250 discrete narrow bands ranging between 392 and 851 nm. The proposed models for the simultaneous analysis of all the bands were ordinal least square (OLS), Bayes B, principal components with Bayes B, functional B-spline, functional Fourier and functional partial least square. The results of these models were compared with the OLS performed using as predictors each of the eight VIs individually and combined. CONCLUSIONS: We found that using all bands simultaneously increased prediction accuracy more than using VI alone. The Splines and Fourier models had the best prediction accuracy for each of the nine time-points under study. Combining image data collected at different time-points led to a small increase in prediction accuracy relative to models that use data from a single time-point. Also, using bands with heritabilities larger than 0.5 only in Drought as predictor variables showed improvements in prediction accuracy.

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