Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures

<p>Abstract</p> <p>Background</p> <p>To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic responses of monodisperse amorphous silica nanoparticles (aSNPs) of 30 nm in size on an <it>in vitro </it>coculture model mimicking the alveolar-capillary barrier and compared these to conventional monocultures.</p> <p>Methods</p> <p>Thus, the epithelial cell line, H441, and the endothelial cell line, ISO-HAS-1, were used in monoculture and in coculture on opposite sides of a filter membrane. Cytotoxicity was evaluated by the MTS assay, detection of membrane integrity (LDH release), and TER (Transepithelial Electrical Resistance) measurement. Additionally, parameters of inflammation (sICAM-1, IL-6 and IL-8 release) and apoptosis markers were investigated.</p> <p>Results</p> <p>Regarding toxic effects (viability, membrane integrity, TER) the coculture model was less sensitive to apical aSNP exposure than the conventional monocultures of the appropriate cells. On the other hand, the <it>in vitro </it>coculture model responded with the release of inflammatory markers in a much more sensitive fashion than the conventional monoculture. At concentrations that were 10-100fold less than the toxic concentrations the apically exposed coculture showed a release of IL-6 and IL-8 to the basolateral side. This may mimic the early inflammatory events that take place in the pulmonary alveoli after aSNP inhalation. Furthermore, a number of apoptosis markers belonging to the intrinsic pathway were upregulated in the coculture following aSNP treatment. Analysis of the individual markers indicated that the cells suffered from DNA damage, hypoxia and ER-stress.</p> <p>Conclusion</p> <p>We present evidence that our <it>in vitro </it>coculture model of the alveolar-capillary barrier is clearly advantageous compared to conventional monocultures in evaluating the extent of damage caused by hazardous material encountering the principle biological barrier in the lower respiratory tract.</p

The Effect of Enriched Environment on the Outcome of Traumatic Brain Injury; A Behavioral, Proteomics, and Histological Study

De novo hippocampal neurogenesis contributes to functional recovery following traumatic brain injury (TBI). Enriched environment (EEN) can improve the outcome of TBI by positively affecting neurogenesis. Blast induced traumatic brain injury (bTBI) characterized by memory impairment and increased anxiety levels, is a leading cause of chronic disability among soldiers. Using a rodent model of bTBI we asked: (a) whether long-term exposure to EEN after injury can ameliorate behavioral abnormalities and (b) what the effects of EEN are at the molecular and cellular levels and on de novo neurogenesis. We found that housing injured animals in EEN resulted in significantly improved spatial memory while animals in normal housing (NH) showed persistent memory impairment. VEGF and Tau protein but not Interleukin-6 (IL-6) levels were normalized in the dorsal hippocampus (DHC) of EEN rats while all three markers remained elevated in NH rats. Interestingly, after peaking at 6 weeks post-injury, anxiety returned to normal levels at 2 months independent of housing conditions. Housing animals in EEN had no significant effect on VEGF and Tau protein levels in the ventral hippocampus (VHC) and the amygdala (AD). We also found that EEN reduced IL-6 and IFNγ levels in the VHC; these markers remained elevated following NH. We observed an increase in GFAP and DCX immunoreactivities in the VHC of NH animals at 2 months post-injury. Conversely, injured animals housed in EEN showed no increase in GFAP or DCX immunoreactivity in their VHC. In summary, long-term exposure of injured animals to EEN appears to play a positive role in the restoration of memory functions but not on anxiety, which returned to normal levels after a significant period of time. Cellular and molecular changes in response to EEN appear to be a part of neurogenesis-independent as well as dependent recovery processes triggered by bTBI

Designing technology tools to support engagement in mindfulness-based interventions: an analysis of teacher and student experiences

Standard mindfulness-based interventions have significant at-home assignments of formal mindfulness practice as a key component. Engagement with formal home practice has been correlated with treatment outcomes, but participants often complete less than the assigned amounts. Here, we explore the requirements for technology tools that can support and encourage home practice, in a way that is appropriate and consistent with the core principles of mindfulness-based interventions. Interviews were held with a group of five highly experienced mindfulness teachers and a group of five participants who had previously completed an eight-week course. Data was subjected to thematic analysis. A key finding was that providing teachers with information on how students practice could support communication around difficulties with home practice. We also identified questions around the appropriateness of adapting the course in response to participant difficulties and participant preferences. Both teachers and students made numerous suggestions for ways to augment their training using technology, such as via practice reminders and provision of teacher-specific content. Finally, a major design issue for technology developers is how to support participants in reflecting on their experiences of mindfulness practice, and subsequent learning, but not to critically evaluate their practice

Coupling commercial fisheries and survey data: a practical solution to boost the amount of information in data-poor context

Quantitative fish stock assessment methods have become increasingly complex. However, the quality of available data may still restrict their applicability, being a particular concern in data-poor situations and where management decisions rely on either commercial fisheries or scientific survey data. In this study we address this issue by proposing a flexible statistical tool that can compare and integrate both datasets simultaneously, and hence boost the amount of information. Because of different sampling designs and procedures, distinct levels of biases arise between datatypes (e.g., different spatio-temporal coverages and size spectra of fish), which are accounted for in our model framework. The model is developed in Template Model Builder, alternatively applied to (i) commercial data, (ii) survey data and (iii) commercial coupled to survey data, and tested on cod, plaice and sprat stocks in the western Baltic Sea (2005-2016). We found that each data type supplied different, yet complementary, information on the species spatio-temporal dynamics. Though the overall spatial pattern in both datatypes showed similar trends, the variability was clearly higher when evaluating the datasets separately, while the coupled dataset was the most informative one. This confirms that the predictive modelling was greatly improved by joining the datasets and will likely enhance future stock evaluation and management advice in both data-poor and data-rich contexts. Moreover, our benchmark tool represents a valuable solution for supporting a robust bio-economic management of fisheries, and enhances the picture we have in data-poor context with spatial and temporal scales that really matters to fisheries policy makers

Smartphone monitoring of participants' engagement with home practice during mindfulness-based stress reduction: Observational study

Background: Standardized mindfulness training courses involve significant at-home assignments of meditation practice. Participants’ self-reported completion of these assignments has been correlated with treatment outcomes, but self-reported data are often incomplete and potentially biased. In addition, mindfulness teachers typically suggest that participants set aside a regular practice time, preferably in the morning, but the extent to which participants do this has not been empirically examined. Objective: This study aimed to analyze patterns of participant engagement with home practice in a mindfulness-based stress reduction course. Methods: We used a novel smartphone app to provide 25 participants with access to their daily practice assignments during the 8-week course. We analyzed data collected through our smartphone app to determine usage and listening patterns and performed analyses of the regularity and frequency of participant behavior. Results: We found that participants listened to a median of 3 of the 6 practice sessions per week, and they did not typically set aside a regular daily practice time. Across weekdays, participants practiced most frequently in the morning, but there was considerable variation in participants’ practice start times. On weekends, the peak practice time was in the evening. Conclusions: We suggest that it is feasible to integrate a smartphone-monitoring approach into existing mindfulness interventions. High-frequency smartphone monitoring can provide insights into how and when participants complete their homework, information that is important in supporting treatment engagement

Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10 -8) and rs9275596 (P=6.8 × 10 -10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD