58 research outputs found
Morning and evening efficacy evaluation of rupatadine (10 and 20 mg), compared with cetirizine 10 mg in perennial allergic rhinitis: a randomized, double-blind, placebo-controlled trial
Rupatadine oral solution for 2-5-year-old children with allergic rhinitis : a safety, open-label, prospective study
There are few clinical trials that assess the efficacy of antihistamines in very young children. Rupatadine is a second-generation antihistamine indicated for the treatment of allergic rhinitis (AR) and urticaria. In this study, AR symptoms were evaluated before and after daily 1 mg/mL rupatadine oral solution administration in 2-5-year-old children. A multicenter open-label study was carried out in 2-5-year-old children with AR. Safety assessments were collected during the study including spontaneous adverse events, vital signs, and electrocardiogram (QTc interval). Additionally, evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion; sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery, and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian before and after 4 weeks of rupatadine administration, dosed according to body weight. A total of 44 children received the study treatment. Only 15 adverse events were reported. All of them were of mild intensity and considered not related to the study treatment. No patient exceeded the standard parameter of >450 ms in the last visit, for the QTc interval on their electrocardiograms. From a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were both statistically significant different (p <0.001) from the baseline T5SS value (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual symptoms, including nasal congestion, showed also a decrease from baseline at both 14 and 28 days. Rupatadine 1 mg/mL oral solution was found to be safe in 2-5-year-old children, correlating with an improvement of AR symptoms, overall and each individually, after a daily dose administration. With this study, we enlarge the available information in this very young pediatric patients' group, in which there is a general lack of clinical evidence
COPD severity score as a predictor of failure in exacerbations of COPD. The ESFERA study
SummaryBackgroundExacerbations are a frequent cause of morbidity and mortality in COPD. It is crucial to identify risk factors for failure after treatment of exacerbations of COPD. This study evaluates the COPD severity score (COPDSS) as a predictor of clinical failure, together with other severity, activity and quality of life measurements, in patients with exacerbated COPD.MethodMulticenter, prospective, observational study in ambulatory patients with exacerbation of COPD. The patients completed the COPDSS, the London Chest Activities of Daily Living (LCADL) and the EuroQol 5D (EQ-5D). A follow-up visit was scheduled one month after presentation with the exacerbation to assess the clinical evolution.ResultsA total of 346 patients were included (mean age 68.5 years (SDÂ =Â 9.5 years and 90.7% male) and mean FEV1(% predicted) 46.9% (SDÂ =Â 17)). After one month, 28.2% of episodes were classified as failures, with half of them requiring hospital admission. Patients who failed were more frequently active smokers, with more severe dyspnoea at presentation and worse lung function. They had significantly worse scores of COPDSS, LCADL, EQ-5D index and EQ-5D visual analogue score (VAS) and shorter mean time walking per day. ROC analysis of relationship between COPDSS and failure gave AUC 0.72, which improved only to 0.77 when the other significant variables in univariate analysis were considered.ConclusionsClinical failure after ambulatory treatment of exacerbation of COPD is frequent. Usual markers of severity (impaired lung function, active smoking and severe dyspnoea) are associated with failure; however, a short severity questionnaire (COPDSS) provides better predictive value than the usual variables
A Quantum Mechanics / Molecular Mechanics Study of the Protein-Ligand Interaction of two potent inhibitors of human O-GlcNAcase: PUGNAc and NAG-thiazoline
O-glycoprotein 2-acetamino-2-deoxy-β-D-glucopyranosidase (O-GlcNAcase)
hydrolyzes 2-acetamido-2-deoxy-β-D-glucopyranose (O-GlcNAc) residues of serine/threonine
residues of modified proteins. O-GlcNAc is present in many intracellular proteins and appears
to have a role in the etiology of several diseases including cancer, Alzheimer’s disease, and
type II diabetes. In this work, we have carried out molecular dynamics (MD) simulations
using a hybrid Quantum Mechanics / Molecular Mechanics (QM/MM) approach, to determine
the binding of two potent inhibitors, PUGNAc and NAG, with a bacterial O-GlcNAcase. The
results of these simulations show that Asp-401, Asp-298 and Asp-297 residues play an
important role in the protein-inhibitor interactions. These results might be useful to design
compounds with more interesting inhibitory activity on the basis of its three-dimensional
structur
Implementation Issues of Adaptive Energy Detection in Heterogeneous Wireless Networks
Abstract
Spectrum sensing (SS) enables the coexistence of non-coordinated heterogeneous wireless systems operating in the same band. Due to its computational simplicity, energy detection (ED) technique has been widespread employed in SS applications; nonetheless, the conventional ED may be unreliable under environmental impairments, justifying the use of ED-based variants. Assessing ED algorithms from theoretical and simulation viewpoints relies on several assumptions and simplifications which, eventually, lead to conclusions that do not necessarily meet the requirements imposed by real propagation environments. This work addresses those problems by dealing with practical implementation issues of adaptive least mean square (LMS)-based ED algorithms. The paper proposes a new adaptive ED algorithm that uses a variable step-size guaranteeing the LMS convergence in time-varying environments. Several implementation guidelines are provided and, additionally, an empirical assessment and validation with a software defined radio-based hardware is carried out. Experimental results show good performance in terms of probabilities of detection (P-d > 0.9) and false alarm (P-f similar to 0.05) in a range of low signal-to-noise ratios around [4, 1] dB, in both single-node and cooperative modes. The proposed sensing methodology enables a seamless monitoring of the radio electromagnetic spectrum in order to provide band occupancy information for an efficient usage among several wireless communications systems.This work has been financially supported in part by the Spanish Ministry of Economy and Competitiveness under Project 5G-NewBROs (TEC2015-66153-P MINECO/FEDER, UE), and in part by the Basque Government (IT-683-13 and ELKARTEK program under BID3A3 and BID3ABI projects) and the European Regional Development Fund, ERDF
Characterization of non-intentional emissions from distributed energy resources up to 500 kHz: A case study in Spain
[EN] Narrow Band Power Line Communications (NB-PLC) systems are currently used for smart metering and power quality monitoring as a part of the Smart Grid (SG) concept. However, non-intentional emissions generated by the devices connected to the grid may sometimes disturb the communications and isolate metering equipment. Though some research works have been recently developed to characterize these emissions, most of them have been limited to frequencies below 150 kHz and they are mainly focused on in-house electronic appliances and lightning devices. As NB-PLC can also be allocated in higher frequencies up to 500 kHz, there is still a lack of analysis in this frequency range, especially for emissions from Distributed Energy Resources (DERs). The identification and characterization of the emissions is essential to develop solutions that avoid a negative impact on the proper performance of NB-PLC. In this work, the non-intentional emissions of different types of DERs composing a representative microgrid have been measured in the 35–500 kHz frequency range and analyzed both in time and frequency domains. Different working conditions and coupling and commutation procedures to mains are considered in the analysis. Results are then compared to the limits recommended by regulatory bodies for spurious emissions from communication systems in this frequency band, as no specific limits for DERs have been established. Field measurements show clear differences in the characteristics of non-intentional emissions for different devices, working conditions and coupling procedures and for frequencies below and above 150 kHz. Results of this study demonstrate that a further characterization of the potential emissions from the different types of DERs connected to the grid is required in order to guarantee current and future applications based on NB-PLC.This work has been financially supported in part by the Basque Government (Elkartek program)
MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles
Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.This work was supported by Carlos III Institute, (PI17/00189 and DTS15/00069), by Fondo Europeo
de Desarrollo Regional—FEDER, by the Gipuzkoa Regional Council (DFG 15/006), by grant from the Basque
Government (RIS3/DTS/2018222025), by the Department of Industry of the Basque Country (ELKARTEK 16/014),
and the Spanish State Research Agency (SAF2017-87670-R) and Maria de Maeztu Units of Excellence Program
Grant MDM-2017-0720). I.O.-Q., A.A. and L.I. were supported by the Department of Education of the Basque
Government. IOQ and LAN were supported by EMBO short Term Fellowship Programme. LAN was supported
by a Canadian graduate scholarship from the Canadian Institutes of Health Research (CGS-D CIHR).PRC was
supported by Ikerbasque, the Basque Foundation for Science
Insight into the antibacterial mechanism of Cu-enriched sol–gel coatings employing proteomics
Advanced antibacterial biomaterials can help reduce the severe consequences of infections. Using copper compounds is an excellent option to achieve this goal; they offer a combination of regenerative and antimicrobial functions. In this study, new CuCl2-doped sol–gel coatings were developed and physicochemically characterised. Their osteogenic and inflammatory responses were tested in vitro using human osteoblasts and THP-1 macrophages. Their antibacterial effect was evaluated using Escherichia coli and Staphylococcus aureus. The Cu influence on the adsorption of human serum proteins was analysed employing proteomics. The materials released Cu2+ and were not cytotoxic. The osteoblasts in contact with these materials showed an increased ALP, BMP2 and OCN gene expression. THP-1 showed an increase in pro-inflammatory markers related to M1 polarization. Moreover, Cu-doped coatings displayed a potent antibacterial behaviour against E. coli and S. aureus. The copper ions affected the adsorption of proteins related to immunity, coagulation, angiogenesis, fibrinolysis, and osteogenesis. Interestingly, the coatings had increased affinity to proteins with antibacterial functions and proteins linked to the complement system activation that can lead to direct bacterial killing via large pore-forming complexes. These results contribute to our understanding of the antibacterial mechanisms of Cu-biomaterials and their interaction with biological systems.This work was supported by Ministerio Ciencia e Innovación [PID2020-113092RB-C21], Generalitat Valenciana [APOSTD/2020/036, PROMETEO/2020/069], Universitat Jaume I [UJI-B2021-25] and Basque Government [MARSA21/07]. The authors would like to thank Raquel Oliver, José Ortega and Iraide Escobés for their valuable technical assistance and GMI-Ilerimplant for making the titanium discs
Outcomes and factors associated with mortality in patients with atrial fibrillation and heart failure: FARAONIC study
Background: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions. Hypothesis: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain. Methods: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled. Results: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 +/- 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA2DS2-VASc was 4.1 +/- 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31). Conclusions: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation
Protein adsorption/desorption dynamics on Ca-enriched titanium surfaces: biological implications
[EN] Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces.This work was supported by MINECO [MAT2017-86043-R; RTC-2017-6147-1], Generalitat Valenciana [GRISOLIAP/2018/091; APOSTD/2020/036, PROMETEO/2020/069], Universitat Jaume I under [ UJI-B2017-37], the University of the Basque Country under [GIU18/189] and Basque Government under [PRE_2017_2_0044]. The authors would like to thank Raquel Oliver, Jose Ortega and Iraide Escobes for their valuable technical assistance.Romero-Gavilán, F.; Cerqueira, A.; Anitua, E.; Tejero, R.; GarcÃa-Arnáez, I.; MartÃnez-Ramos, C.; Ozturan, S.... (2021). Protein adsorption/desorption dynamics on Ca-enriched titanium surfaces: biological implications. JBIC Journal of Biological Inorganic Chemistry. 26(6):1-12. https://doi.org/10.1007/s00775-021-01886-4S11226
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