2,665 research outputs found

    Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

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    Background: Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties. Purpose: This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine–glycine–aspartic acid) and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Materials and methods: SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered intrarectally to TNBS-induced colitic rats for 7 days. Results: The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the expression of different pro-inflammatory cytokines (interleukin IL]-1ß, IL-6, and IL-12) and inducible nitric oxide synthase in comparison with the TNBS control group. Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1 and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN treatment. However, both treatments improved the intestinal wall integrity by increasing the gene expression of some of its markers (trefoil factor-3 and mucins). Conclusion: SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats, which were improved by functionalization with the RGD peptide

    Adaptation of antibiotic treatment to clinical practice guidelines in patients aged ⩾65 years hospitalised due to community-acquired pneumonia

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    [EN] Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013–14 and 2014–15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1–53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15–1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25–2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1–56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03–7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.S

    Language Identification in Short Utterances Using Long Short-Term Memory (LSTM) Recurrent Neural Networks

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    Zazo R, Lozano-Diez A, Gonzalez-Dominguez J, T. Toledano D, Gonzalez-Rodriguez J (2016) Language Identification in Short Utterances Using Long Short-Term Memory (LSTM) Recurrent Neural Networks. PLoS ONE 11(1): e0146917. doi:10.1371/journal.pone.0146917Long Short Term Memory (LSTM) Recurrent Neural Networks (RNNs) have recently outperformed other state-of-the-art approaches, such as i-vector and Deep Neural Networks (DNNs), in automatic Language Identification (LID), particularly when dealing with very short utterances (similar to 3s). In this contribution we present an open-source, end-to-end, LSTM RNN system running on limited computational resources (a single GPU) that outperforms a reference i-vector system on a subset of the NIST Language Recognition Evaluation (8 target languages, 3s task) by up to a 26%. This result is in line with previously published research using proprietary LSTM implementations and huge computational resources, which made these former results hardly reproducible. Further, we extend those previous experiments modeling unseen languages (out of set, OOS, modeling), which is crucial in real applications. Results show that a LSTM RNN with OOS modeling is able to detect these languages and generalizes robustly to unseen OOS languages. Finally, we also analyze the effect of even more limited test data (from 2.25s to 0.1s) proving that with as little as 0.5s an accuracy of over 50% can be achieved.This work has been supported by project CMC-V2: Caracterizacion, Modelado y Compensacion de Variabilidad en la Señal de Voz (TEC2012-37585-C02-01), funded by Ministerio de Economia y Competitividad, Spain

    Anosognosia in Amnestic Mild Cognitive Impairment is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia:Preliminary MRI Findings

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    Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer’s disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (n = 6), aMCI subjects without anosognosia (n = 12), AD subjects with anosognosia (n = 6), and AD subjects without anosognosia (n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology

    A western route of prehistoric human migration from Africa into the Iberian Peninsula

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    Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar

    MAGIC observations of MWC 656, the only known Be/BH system

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    Context: MWC 656 has recently been established as the first observationally detected high-mass X-ray binary system containing a Be star and a black hole (BH). The system has been associated with a gamma-ray flaring event detected by the AGILE satellite in July 2010. Aims: Our aim is to evaluate if the MWC 656 gamma-ray emission extends to very high energy (VHE > 100 GeV) gamma rays. Methods. We have observed MWC 656 with the MAGIC telescopes for \sim23 hours during two observation periods: between May and June 2012 and June 2013. During the last period, observations were performed contemporaneously with X-ray (XMM-Newton) and optical (STELLA) instruments. Results: We have not detected the MWC 656 binary system at TeV energies with the MAGIC Telescopes in either of the two campaigns carried out. Upper limits (ULs) to the integral flux above 300 GeV have been set, as well as differential ULs at a level of \sim5% of the Crab Nebula flux. The results obtained from the MAGIC observations do not support persistent emission of very high energy gamma rays from this system at a level of 2.4% the Crab flux.Comment: Accepted for publication in A&A. 5 pages, 2 figures, 2 table
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