Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

Indexación: Web of Science; Scopus; Scielo.Background: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3). Results: As a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents. Conclusions: Our results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0241-

The SARS-CoV-2 Infection Among Students in the University of Porto: A Cross-Sectional Study

Objective: We aimed to quantify SARS-CoV-2 specific antibodies’ seroprevalence among university students in Porto. Methods: A rapid point of care testing for SARS-CoV-2 specific immunoglobulin (Ig) M and IgG antibodies was performed, and a questionnaire was applied to 6512 voluntary students from September to December 2020. We computed the apparent IgM, IgG, and IgM or IgG prevalence, and the true prevalence and 95% credible intervals (95% CI) using Bayesian inference. Results: We found an apparent prevalence (IgM or IgG) of 9.7%, the true prevalence being 7.9% (95% CI 4.9–11.1). Prevalence was significantly higher among males (10.9% vs. 9.2%), international students (18.1% vs. 10.4% local vs. 8.8% nationally displaced), and increased with age. Those with a known risk contact, that experienced quarantine, had symptoms, or a previous negative molecular test had a higher seroprevalence. Of the 91 (1.4%) students who reported a molecular diagnosis, 86.8% were reactive for IgM or IgG. Conclusion: Based on immunological evidence infection was 5.6-fold the reported molecular diagnosis. The higher seroprevalence among male, older, and international students emphasizes the importance of identifying particular groups. Copyright © 2022 Meireles, Costa, Novais, Miranda, Lopes, Severo and Barros.This study was funded by University of Porto and supported by national funds of Fundação para a Ciência e Tecnologia, under the scope of the projects UIDB/04750/2020—Research Unit of Epidemiology–Institute of Public Health of the University of Porto (EPIUnit) and LA/P/0064/2020–Laboratory for Integrative and Translational Research in Population Health (ITR). JPC was the recipient of PhD grant (DFA/BD/8562/2020) co-funded by the national funds of Fundação para a Ciência e Tecnologia and the Fundo Social Europeu

Factors associated with the impact of quality improvement collaboratives in mental healthcare: An exploratory study

<p>Abstract</p> <p>Background</p> <p>Quality improvement collaboratives (QICs) bring together groups of healthcare professionals to work in a structured manner to improve the quality of healthcare delivery within particular domains. We explored which characteristics of the composition, participation, functioning, and organization of these collaboratives related to changes in the healthcare for patients with anxiety disorders, dual diagnosis, or schizophrenia.</p> <p>Methods</p> <p>We studied three QICs involving 29 quality improvement (QI) teams representing a number of mental healthcare organizations in the Netherlands. The aims of the three QICs were the implementation of multidisciplinary practice guidelines in the domains of anxiety disorders, dual diagnosis, and schizophrenia, respectively. We used eight performance indicators to assess the impact of the QI teams on self-reported patient outcomes and process of care outcomes for 1,346 patients. The QI team members completed a questionnaire on the characteristics of the composition, participation in a national program, functioning, and organizational context for their teams. It was expected that an association would be found between these team characteristics and the quality of care for patients with anxiety disorders, dual diagnosis, and schizophrenia.</p> <p>Results</p> <p>No consistent patterns of association emerged. Theory-based factors did not perform better than practice-based factors. However, QI teams that received support from their management and both active and inspirational team leadership showed better results. Rather surprisingly, a lower average level of education among the team members was associated with better results, although less consistently than the management and leadership characteristics. Team views with regard to the QI goals of the team and attitudes towards multidisciplinary practice guidelines did not correlate with team success.</p> <p>Conclusions</p> <p>No general conclusions about the impact of the characteristics of QI teams on the quality of healthcare can be drawn, but support of the management and active, inspirational team leadership appear to be important. Not only patient outcomes but also the performance indicators of monitoring and screening/assessment showed improvement in many but not all of the QI teams with such characteristics. More studies are needed to identify factors associated with the impact of multidisciplinary practice guidelines in mental healthcare.</p

Heat Treated NiP–SiC Composite Coatings: Elaboration and Tribocorrosion Behaviour in NaCl Solution

Tribocorrosion behaviour of heat-treated NiP and NiP–SiC composite coatings was investigated in a 0.6 M NaCl solution. The tribocorrosion tests were performed in a linear sliding tribometer with an electrochemical cell interface. It was analyzed the influence of SiC particles dispersion in the NiP matrix on current density developed, on coefficient of friction and on wear volume loss. The results showed that NiP–SiC composite coatings had a lower wear volume loss compared to NiP coatings. However, the incorporation of SiC particles into the metallic matrix affects the current density developed by the system during the tribocorrosion test. It was verified that not only the volume of co-deposited particles (SiC vol.%) but also the number of SiC particles per coating area unit (and consequently the SiC particles size) have made influence on the tribocorrosion behaviour of NiP–SiC composite coatings

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA

Laser welding of Cu-Al-Be shape memory alloys: Microstructure and mechanical properties

Cu-based shape memory alloys are potential substitutes of NiTi shape memory alloys, owing to their lower production costs and recent increase inmechanical properties arising frombetter control of the microstructure. The development of joining technologies for advancedmaterials is key to expand to the potential applications of any engineering alloy. In thiswork, laserwelding of single crystal-like Cu-Al-Be shapememory alloys was performed. The microstructure and tensile propertieswere evaluated to understand the effect of laserwelding on the microstructural and mechanical features of thewelded joints. Cycling tests performed for awide range of temperatures revealed that the joints possess extraordinary superelastic recovery after joining, with potential applications in damping devices due to the significant amount of energy that can be absorbed during superelastic deformation

Pedagogy of hate

Written as an extended review of Peter McLaren’s 'Pedagogy of Insurrection: from Resurrection to Revolution’ published in 2015, this paper contradicts McLaren’s affirmation of political religion and the version of critical pedagogy on which it is based, claiming hate rather than Christian love as a core concept of Critical Theory. Not a personal, psychological or pathological hate, but a radical hate for what the world has become, or absolute negativity. Hate must be invoked as love-hate for the magic of dialectics to work against the holy love of McLaren’s Christian socialism. Radical hate reveals the main transcendental tenets of capitalist civilisation: God and Money, as impersonal forms of social domination that must be brought down to earth so real existence can learn, learn, learn itself. That is the educative power of the Pedagogy of Hate. Now and forever

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Regional perinatal mortality differences in the Netherlands; care is the question

Background. Perinatal mortality is an important indicator of health. European comparisons of perinatal mortality show an unfavourable position for the Netherlands. Our objective was to study regional variation in perinatal mortality within the Netherlands and to identify possible explanatory factors for the found differences. Methods. Our study population comprised of all singleton births (904,003) derived from the Netherlands Perinatal Registry for the period 2000-2004. Perinatal mortality including stillbirth from 22+0weeks gestation and early neonatal death (0-6 days) was our main outcome measure. Differences in perinatal mortality were calculated between 4 distinct geographical regions North-East-South-West. We tried to explain regional differences by adjustment for the demographic factors maternal age, parity and ethnicity and by socio-economic status and urbanisation degree using logistic modelling. In addition, regional differences in mode of delivery and risk selection were analysed as health care factors. Finally, perinatal mortality was analysed among five distinct clinical risk groups based on the mediating risk factors gestational age and congenital anomalies. Results. Overall perinatal mortality was 10.1 per 1,000 total births over the period 2000-2004. Perinatal mortality was elevated in the northern region (11.2 per 1,000 total births). Perinatal mortality in the eastern, western and southern region was 10.2, 10.1 and 9.6 per 1,000 total births respectively. Adjustment for demographic factors increased the perinatal mortality risk in the northern region (odds ratio 1.20, 95% CI 1.12-1.28, compared to reference western region), subsequent adjustment for socio-economic status and urbanisation explained a small part of the elevated risk (odds ratio 1.11, 95% CI 1.03-1.20). Risk group analysis showed that regional differences were absent among very preterm births (22+0- 25+6weeks gestation) and most prominent among births from 32+0gestation weeks onwards and among children with severe congenital anomalies. Among term births (37+0weeks) regional mortality differences were largest for births in women transferred from low to high risk during delivery. Conclusion. Regional differences in perinatal mortality exist in the Netherlands. These differences could not be explained by demographic or socio-economic factors, however clinical risk group analysis showed indications for a role of health care factors