Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (/dL) and ESL 1200 mg QD (/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. SIGNIFICANCE: These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations

Monitoring Arthropods in maize and pasture fields in São Miguel and São Jorge Islands: IPM-Popillia Project

ABSTRACT: The dataset presented here is an achievement of the H2020 European project "Integrated Pest Management of the Invasive Japanese Beetle, Popillia japonica (IPM-Popillia)". This project addresses the challenge of a new risk to plant health in Europe, the invasion of the Japanese beetle, Popillia japonica (Newman, 1838) (Coleoptera, Rutelidae) and provides an environmentally friendly IPM Toolbox to control the expanding pest populations across Europe. This study aims to present the records of terrestrial arthropod diversity with a special focus on four groups belonging to Carabids and Staphylinid beetles (Coleoptera), Opiliones and Anisolabididae (Dermaptera), collected with the potential to be used as biocontrol agents against P. japonica in future Integrated Pest Management programmes. A thorough sampling programme was conducted in maize and pasture fields in two Islands of the Azores (São Miguel and São Jorge) in the summer of 2022.info:eu-repo/semantics/publishedVersio

Student's perceptions of flipped classroom approach: results from an educational innovation project

The Flipped Classroom model is well known and recognized, and its popularity seems to keep increasing. In this pedagogical model, the transmission of conceptual knowledge is left to individual tasks outside the classroom while the contact hours, inside the classroom, are completely opened to problem solving, active and peer-assisted learning. The purpose of this work is to describe an educational innovative experience that began in the academic year 2015-2016 with the University of Malaga's Educational Innovation Project PIE15/174 (UMA), based on Flipped Classroom and gamification in a collaborative system among its students. This project has been renewed and extended over the years, with the integration of more teachers and subjects from both the UMA and the Polytechnic University of Porto, up until the current PIE19/156. Further, the aim is to examine the degree of student satisfaction with the strategies and methodologies applied in class, paying special attention to the general aspects and the level of extension of the pedagogical model in each subject. Some statistical analysis of students' satisfaction with the pedagogical model's application are presented. The results are promising and gratifying for all teachers involved, since these show a high degree of satisfaction with the teaching model and the strategy implementation.info:eu-repo/semantics/publishedVersio

MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

[EN] Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with Tc-99m (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. (C) 2017 Elsevier Inc. All rights reserved.Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged.Pascual, L.; Cerqueira, C.; García-Fernández, A.; De Luis-Fernández, B.; Soares, E.; Souza, M.; Missailidis, S.... (2017). MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications. Nanomedicine Nanotechnology Biology and Medicine. 13(8):2495-2505. https://doi.org/10.1016/j.nano.2017.08.006S2495250513

Changes of energy fluxes in marine animal forests of the anthropocene: Factors shaping the future seascape

Climate change is already transforming the seascapes of our oceans by changing the energy availability and the metabolic rates of the organisms. Among the ecosystem-engineering species that structure the seascape, marine animal forests (MAFs) are the most widespread. These habitats, mainly composed of suspension feeding organisms, provide structural complexity to the sea floor, analogous to terrestrial forests. Because primary and secondary productivity is responding to different impacts, in particular to the rapid ongoing environmental changes driven by climate change, this paper presents some directions about what could happen to different MAFs depending on these fast changes. Climate change could modify the resistance or resilience of MAFs, potentially making them more sensitive to impacts from anthropic activities (i.e. fisheries and coastal management), and vice versa, direct impacts may amplify climate change constraints in MAFs. Such changes will have knock-on effects on the energy budgets of active and passive suspension feeding organisms, as well as on their phenology, larval nutritional condition, and population viability. How the future seascape will be shaped by the new energy fluxes is a crucial question that has to be urgently addressed to mitigate and adapt to the diverse impacts on natural systems

A New Sugarcane Cystatin Strongly Binds to Dental Enamel and Reduces Erosion.

Cystatin B was recently identified as an acid-resistant protein in acquired enamel pellicle; it could therefore be included in oral products to protect against caries and erosion. However, human recombinant cystatin is very expensive, and alternatives to its use are necessary. Phytocystatins are reversible inhibitors of cysteine peptidases that are found naturally in plants. In plants, they have several biological and physiological functions, such as the regulation of endogenous processes, defense against pathogens, and response to abiotic stress. Previous studies performed by our research group have reported high inhibitory activity and potential agricultural and medical applications of several sugarcane cystatins, including CaneCPI-1, CaneCPI-2, CaneCPI-3, and CaneCPI-4. In the present study, we report the characterization of a novel sugarcane cystatin, named CaneCPI-5. This cystatin was efficiently expressed in Escherichia coli, and inhibitory assays demonstrated that it was a potent inhibitor of human cathepsins B, K, and L ( Ki = 6.87, 0.49, and 0.34 nM, respectively). The ability of CaneCPI-5 to bind to dental enamel was evaluated using atomic force microscopy. Its capacity to protect against initial enamel erosion was also tested in vitro via changes in surface hardness. CaneCPI-5 showed a very large force of interaction with enamel (e.g., compared with mucin and casein) and significantly reduced initial enamel erosion. These results suggest that the inclusion of CaneCPIs in dental products might confer protection against enamel erosion.This research was supported by the São Paulo Research Foundation (FAPESP) (CEPID-CBME #98/14138-2) and by the Royal Society (Newton Advanced Fellowship #NA140459). A.C.S. is a recipient of a scholarship from the National Council for Scientific and Technological Development (CNPq). M.C.M. received a grant from the Coordination for the Improvement of Higher Education Personnel (CAPES). V.T.P. received a grant from the FAPESP. F.H.-S. and M.A.R.B. were recipients of a productivity scholarship from the CNPq

Changes of energy fluxes in marine animal forests of the Anthropocene: factors shaping the future seascape

Climate change is already transforming the seascapes of our oceans by changing the energy availability and the metabolic rates of the organisms. Among the ecosystem-engineering species that structure the seascape, marine animal forests (MAFs) are the most widespread. These habitats, mainly composed of suspension feeding organisms, provide structural complexity to the sea floor, analogous to terrestrial forests. Because primary and secondary productivity is responding to different impacts, in particular to the rapid ongoing environmental changes driven by climate change, this paper presents some directions about what could happen to different MAFs depending on these fast changes. Climate change could modify the resistance or resilience of MAFs, potentially making them more sensitive to impacts from anthropic activities (i.e. fisheries and coastal management), and vice versa, direct impacts may amplify climate change constraints in MAFs. Such changes will have knock-on effects on the energy budgets of active and passive suspension feeding organisms, as well as on their phenology, larval nutritional condition, and population viability. How the future seascape will be shaped by the new energy fluxes is a crucial question that has to be urgently addressed to mitigate and adapt to the diverse impacts on natural systems.Funding Agency European Union (EU) 327845 ICTA "Unit of Excellence" (MinECo) MDM2015-0552 CALMED project CTM2016-79547-R AGAUR Generalitat de Catalunya (MERS) 2017 SGR 1588 National Council for Scientific and Technological Development (CNPq)info:eu-repo/semantics/publishedVersio

Favourable Influence of Hydrophobic Surfaces on Protein Structure in Porous Organically-Modified Silica Glasses

Organically-modified siloxanes were used as host materials to examine the influence of surface chemistry on protein conformation in a crowded environment. The sol–gel materials were prepared from tetramethoxysilane and a series of monosubstituted alkoxysilanes, RSi(OR′)3, featuring alkyl groups of increasing chain length in the R-position. Using circular dichroism spectroscopy in the far-UV region, apomyoglobin was found to transit from an unfolded state to a native-like helical state as the content of the hydrophobic precursor increased from 0 to 15%. At a fixed molar content of 5% RSi(OR′)3, the helical structure of apomyoglobin increased with the chain length of the R-group, i.e. methyl \u3c ethyl \u3c n-propyl \u3c n-butyl \u3c n-hexyl. This trend also was observed for the tertiary structure of ribonuclease A, suggesting that protein folding and biological activity are sensitive to the hydrophilic/hydrophobic balance of neighboring surfaces. The observed changes in protein structure did not correlate with total surface area or the average pore size of the modified glasses, but scanning electron microscopy images revealed an interesting relationship between surface morphology and alkyl chain length. The unexpected benefit of incorporating a low content of hydrophobic groups into a hydrophilic surface may lead to materials with improved biocompatibility for use in biosensors and implanted devices

Exercise training in the aerobic/anaerobic metabolic transition prevents glucose intolerance in alloxan-treated rats

<p>Abstract</p> <p>Background</p> <p>Ninety percent of cases of diabetes are of the slowly evolving non-insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one of the main causes of this disorder. In this study we analyzed the effects of physical exercise on glucose homeostasis in adult rats with type 2 diabetes induced by a neonatal injection of alloxan.</p> <p>Methods</p> <p>Female Wistar rats aged 6 days were injected with either 250 mg/kg of body weight of alloxan or citrate buffer 0.01 M (controls). After weaning, half of the animals in each group were subjected to physical training adjusted to meet the aerobic-anaerobic metabolic transition by swimming 1 h/day for 5 days a week with weight overloads. The necessary overload used was set and periodically readjusted for each rat through effort tests based on the maximal lactate steady state procedure. When aged 28, 60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their peripheral insulin sensitivity was evaluated using the HOMA index.</p> <p>Results</p> <p>The area under the serum glucose curve obtained through GTT was always higher in alloxan-treated animals than in controls. A decrease in this area was observed in trained alloxan-treated rats at 90 and 120 days old compared with non-trained animals. At 90 days old the trained controls showed lower HOMA indices than the non-trained controls.</p> <p>Conclusion</p> <p>Neonatal administration of alloxan induced a persistent glucose intolerance in all injected rats, which was successfully counteracted by physical training in the aerobic/anaerobic metabolic transition.</p

No short-cut in assessing trial quality: a case study

Assessing the quality of included trials is a central part of a systematic review. Many check-list type of instruments for doing this exist. Using a trial of antibiotic treatment for acute otitis media, Burke et al., BMJ, 1991, as the case study, this paper illustrates some limitations of the check-list approach to trial quality assessment. The general verdict from the check list type evaluations in nine relevant systematic reviews was that Burke et al. (1991) is a good quality trial. All relevant meta-analyses extensively used its data to formulate therapeutic evidence. My comprehensive evaluation, on the other hand, brought to the surface a series of serious problems in the design, conduct, analysis and report of this trial that were missed by the earlier evaluations. A check-list or instrument based approach, if used as a short-cut, may at times rate deeply flawed trials as good quality trials. Check lists are crucial but they need to be augmented with an in-depth review, and where possible, a scrutiny of the protocol, trial records, and original data. The extent and severity of the problems I uncovered for this particular trial warrant an independent audit before it is included in a systematic review