Push-Out Bond Strength of Glass Fiber Endodontic Posts with Different Diameters.

(1) Background: The retention of intraradicular posts is an important factor for the prognosis of endodontically treated teeth. The purpose of this study was to evaluate the push-out bond strength (PBS) of the posts relating to their diameter and region of the root. (2) Methods: A total of 40 premolar teeth (decoronated and root canal-filled) were divided into four groups (n = 10). After post-space preparation, different sizes (1.0, 1.2, 1.5, and 2.0 mm) of glass fiber posts were luted with resin cement into the root canals. After placement, 2 mm thick slices were cut from the roots according to their apical, middle, and coronal regions (n = 116). Push-out tests were carried out in a universal testing machine on each slice. A statistical evaluation of the data was applied. (3) Results: When comparing the diameter, the 2.0 mm posts had the highest PBS (111.99 ± 10.40 N), while the 1.0 mm posts had the lowest PBS (99.98 ± 8.05 N). Divided by the surface of the bonded area, the average PBS value was the highest for the 1.0 mm posts (18.20 ± 1.67 MPa) and the lowest for the 2.0 mm posts (12.08 ± 1.05 MPa). (4) Conclusions: Within the limitations of the study, when comparing the regions of the roots, no significant differences were found among the PBS values of the three regions (p = 0.219). When comparing the diameters, significant differences were shown between the PBS values of the four groups (p = 0.023 and p = 0.003, respectively).

A streamlined approach to structure elucidation using in cellulo crystallized recombinant proteins, InCellCryst.

With the advent of serial X-ray crystallography on microfocus beamlines at free-electron laser and synchrotron facilities, the demand for protein microcrystals has significantly risen in recent years. However, by in vitro crystallization extensive efforts are usually required to purify proteins and produce sufficiently homogeneous microcrystals. Here, we present InCellCryst, an advanced pipeline for producing homogeneous microcrystals directly within living insect cells. Our baculovirus-based cloning system enables the production of crystals from completely native proteins as well as the screening of different cellular compartments to maximize chances for protein crystallization. By optimizing cloning procedures, recombinant virus production, crystallization and crystal detection, X-ray diffraction data can be collected 24 days after the start of target gene cloning. Furthermore, improved strategies for serial synchrotron diffraction data collection directly from crystals within living cells abolish the need to purify the recombinant protein or the associated microcrystals.

Monocyte populations are involved in the pathogenesis of experimental epidermolysis bullosa acquisita.

Monocytes play a significant role in the pathogenesis of most inflammatory diseases, including autoimmune diseases. Herein, different subpopulations of monocytes often play differential, partially antagonistic roles, in the regulation of tissue populations. Pemphigoid diseases constitute a group of autoimmune blistering skin diseases featuring a marked infiltration of the dermis with immune cells, including monocytes. The monocyte subsets infiltrating the skin, however, have largely remained elusive. Monocyte adhesion and recruitment into the inflamed tissues are regulated by chemokine receptors, most prominently by CCR2 and CX3CR1. To delineate the involvement of monocyte populations in autoimmune blistering skin diseases, we spatiotemporally monitored the dynamic spectrum of monocyte populations that infiltrate the inflamed skin using multiphoton intravital imaging and reporter mice for chemokine receptors. Experimental epidermolysis bullosa acquisita (EBA) was induced by injection of anti-murine type VII collagen (amCOLVII) IgG into the Csf1rEGFP-reporter mice, where circulating myeloid cells, such as monocytes and neutrophils, express an EGFP. EGFP+ cells, including neutrophils and monocytes, were present in the skin, immediately after the deposition of the amCOLVII antibody at the dermal-epidermal junction. To investigate the recruitment and involvement of different monocyte-derived cell populations in the disease course further, EBA was induced in CCR2RFP/+-reporter and CX3CR1GFP/+-reporter mice. A comparable distribution of red fluorescent protein (RFP)+ or green fluorescent protein (GFP)+ was found in both diseased mice and their respective controls over time, indicating the similar recruitment of monocytes into the skin following the binding of autoantibodies. Experiments were extended to the CCR2RFP/RFP-deficient and CX3CR1GFP/GFP-deficient mice to determine whether monocyte recruitment and disease severity are compromised in the absence of the receptor. A comparable pattern was seen in the recruitment of monocytes into the skin in both reporter and deficient mice. However, in contrast to similar disease severity between CX3CR1-deficient and reporter mice, CCR2-deficient mice developed significantly less disease than CCR2-reporter mice, as indicated by the percentage of affected area of ears. Collectively, our observations indicate that while CCR2 and CX3CR1 receptors are not involved in the recruitment of monocytes into the skin, CCR2 deficiency is associated with improved disease outcomes in experimental EBA in mice.

Webcam eye tracking close to laboratory standards: Comparing a new webcam-based system and the EyeLink 1000.

This paper aims to compare a new webcam-based eye-tracking system, integrated into the Labvanced platform for online experiments, to a "gold standard" lab-based eye tracker (EyeLink 1000 - SR Research). Specifically, we simultaneously recorded data with both eye trackers in five different tasks, analyzing their real-time performance. These tasks were a subset of a standardized test battery for eye trackers, including a Large Grid task, Smooth Pursuit eye movements, viewing natural images, and two Head Movements tasks (roll, yaw). The results show that the webcam-based system achieved an overall accuracy of 1.4°, and a precision of 1.1° (standard deviation (SD) across subjects), an error of about 0.5° larger than the EyeLink system. Interestingly, both accuracy (1.3°) and precision (0.9°) were slightly better for centrally presented targets, the region of interest in many psychophysical experiments. Remarkably, the correlation of raw gaze samples between the EyeLink and webcam-based was at about 90% for the Large Grid task and about 80% for Free View and Smooth Pursuit. Overall, these results put the performance of the webcam-based system roughly on par with mobile eye-tracking devices (Ehinger et al. PeerJ, 7, e7086, 2019; Tonsen et al., 2020) and demonstrate substantial improvement compared to existing webcam eye-tracking solutions (Papoutsaki et al., 2017).

Predicting group benefits in joint multiple object tracking : Predicting group benefits.

In everyday life, people often work together to accomplish a joint goal. Working together is often beneficial as it can result in a higher performance compared to working alone - a so-called "group benefit". While several factors influencing group benefits have been investigated in a range of tasks, to date, they have not been examined collectively with an integrative statistical approach such as linear modeling. To address this gap in the literature, we investigated several factors that are highly relevant for group benefits (i.e., task feedback, information about the co-actor's actions, the similarity in the individual performances, and personality traits) and used these factors as predictors in a linear model to predict group benefits in a joint multiple object tracking (MOT) task. In the joint MOT task, pairs of participants jointly tracked the movements of target objects among distractor objects and, depending on the experiment, either received group performance feedback, individual performance feedback, information about the group member's performed actions, or a combination of these types of information. We found that predictors collectively account for half of the variance and make non-redundant contributions towards predicting group benefits, suggesting that they independently influence group benefits. The model also accurately predicts group benefits, suggesting that it could be used to anticipate group benefits for individuals that have not yet performed a joint task together. Given that the investigated factors are relevant for other joint tasks, our model provides a first step towards developing a more general model for predicting group benefits across several shared tasks.

NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis.

BACKGROUND: The origin of αSMA-positive myofibroblasts, key players within organ fibrosis, is still not fully elucidated. Pericytes have been discussed as myofibroblast progenitors in several organs including the lung. METHODS: Using tamoxifen-inducible PDGFRß-tdTomato mice (PDGFRß-CreERT2; R26tdTomato) lineage of lung pericytes was traced. To induce lung fibrosis, a single orotracheal dose of bleomycin was given. Lung tissue was investigated by immunofluorescence analyses, hydroxyproline collagen assay and RT-qPCR. RESULTS: Lineage tracing combined with immunofluorescence for nitric oxide-sensitive guanylyl cyclase (NO-GC) as marker for PDGFRß-positive pericytes allows differentiating two types of αSMA-expressing myofibroblasts in murine pulmonary fibrosis: (1) interstitial myofibroblasts that localize in the alveolar wall, derive from PDGFRß+ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRß de novo after injury), are negative for NO-GC, have a large multipolar shape and appear to spread over several alveoli within the injured areas. Moreover, NO-GC expression is reduced during fibrosis, i.e., after pericyte-to-myofibroblast transition. CONCLUSION: In summary, αSMA/PDGFRß-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.

My hands are running away - learning a complex nursing skill via virtual reality simulation: a randomised mixed methods study.

BACKGROUND: Clinical skills training is an essential component of nursing education. However, sometimes education does not sufficiently prepare nurses for the real world. Virtual reality (VR) is an innovative method to complement existing learning strategies, yet few studies investigate its effectiveness. This study compared educational outcomes achieved by three groups learning with either of two different VR simulation variants, with varying technological features, or a video training on the endotracheal suctioning skill. METHODS: The investigated outcomes were knowledge and skill acquisition, learner satisfaction, and technology acceptance. 131 undergraduate nursing students were randomised into three groups, based on the interventions they received. Knowledge was assessed through a pre-post-test design, skill through a post-intervention objective structured clinical examination on a manikin, learning satisfaction and technology acceptance through standardised questionnaires, and qualitative feedback through focus groups. RESULTS: All interventions led to a significant knowledge acquisition, with no significant difference between the groups. The video intervention group performed significantly better than the VR groups in skill demonstration. One of the two VR intervention groups had a significantly higher learner satisfaction than the video group. Technology acceptance was high for both VR groups, with the simpler VR simulation resulting in higher technology acceptance than the one with more experimental features. Students described the VR experience as realistic, interactive, and immersive, and saw the opportunity to practise skills in a safe environment, learn from mistakes, and increase knowledge and confidence. CONCLUSIONS: For the development of VR trainings, we recommend keeping them simple and targeting a specific educational outcome since trying to optimise for multiple outcomes is resource intensive and hard to achieve. Psychomotor skills were easier for participants to learn by watching a video on the procedure rather than practically learning it with the VR hardware, which is a more abstract representation of reality. We therefore recommend using VR as a complementing resource to skills labs, rather than replacing existing learning strategies. Perhaps VR is not ideal for practising practical psychomotor skills at the moment, but it can increase knowledge, satisfaction, motivation, confidence and prepare for further practical training. TRIAL REGISTRATION: Not applicable.

Improved Spatial Knowledge Acquisition through Sensory Augmentation.

Sensory augmentation provides novel opportunities to broaden our knowledge of human perception through external sensors that record and transmit information beyond natural perception. To assess whether such augmented senses affect the acquisition of spatial knowledge during navigation, we trained a group of 27 participants for six weeks with an augmented sense for cardinal directions called the feelSpace belt. Then, we recruited a control group that did not receive the augmented sense and the corresponding training. All 53 participants first explored the Westbrook virtual reality environment for two and a half hours spread over five sessions before assessing their spatial knowledge in four immersive virtual reality tasks measuring cardinal, route, and survey knowledge. We found that the belt group acquired significantly more accurate cardinal and survey knowledge, which was measured in pointing accuracy, distance, and rotation estimates. Interestingly, the augmented sense also positively affected route knowledge, although to a lesser degree. Finally, the belt group reported a significant increase in the use of spatial strategies after training, while the groups' ratings were comparable at baseline. The results suggest that six weeks of training with the feelSpace belt led to improved survey and route knowledge acquisition. Moreover, the findings of our study could inform the development of assistive technologies for individuals with visual or navigational impairments, which may lead to enhanced navigation skills and quality of life.

Action affordance affects proximal and distal goal-oriented planning.

Visual attention is mainly goal directed and allocated based on the upcoming action. However, it is unclear how far this feature of gaze behaviour generalizes in more naturalistic settings. The present study investigates the influence of action affordances on active inference processes revealed by eye movements during interaction with familiar and novel tools. In a between-subject design, a cohort of participants interacted with a virtual reality controller in a low-realism environment; another performed the task with an interaction setup that allowed differentiated hand and finger movements in a high-realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool's effector part before action initiation when asked to produce tool-specific movements, especially with unfamiliar tools. These findings suggest that fixations are made in a task-oriented way to plan the distal goals of producing the task- and tool-specific actions well before action initiation. Moreover, with more realistic action affordance, fixations were biased towards the tool handle when it was oriented incongruent with the subjects' handedness. We hypothesize that these fixations are made towards the proximal goal of planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma.

BACKGROUND: Pulmonary eosinophils comprise at least two distinct populations of resident eosinophils (rEOS) and inflammatory eosinophils (iEOS), the latter recruited in response to pulmonary inflammation. Here, we determined the impact of complement activation on rEOS and iEOS trafficking and function in two models of pulmonary inflammation. METHODS: BALB/c wild-type and C5ar1-/- mice were exposed to different allergens or IL-33. Eosinophil populations in the airways, lung, or mediastinal lymph nodes (mLN) were characterized by FACS or immunohistochemistry. rEOS and iEOS functions were determined in vivo and in vitro. RESULTS: HDM and IL-33 exposure induced a strong accumulation of iEOS but not rEOS in the airways, lungs, and mLNs. rEOS and iEOS expressed C3/C5 and C5aR1, which were significantly higher in iEOS. Initial pulmonary trafficking of iEOS was markedly reduced in C5ar1-/- mice and associated with less IL-5 production from ILC2 cells. Functionally, adoptively transferred pulmonary iEOS from WT but not from C5ar1-/- mice-induced airway hyperresponsiveness (AHR), which was associated with significantly reduced C5ar1-/- iEOS degranulation. Pulmonary iEOS but not rEOS were frequently associated with T cells in lung tissue. After HDM or IL-33 exposure, iEOS but not rEOS were found in mLNs, which were significantly reduced in C5ar1-/- mice. C5ar1-/- iEOS expressed less costimulatory molecules, associated with a decreased potency to drive antigen-specific T cell proliferation and differentiation into memory T cells. CONCLUSIONS: We uncovered novel roles for C5aR1 in iEOS trafficking and activation, which affects key aspects of allergic inflammation such as AHR, ILC2, and T cell activation.

Delayed Microbial Maturation Durably Exacerbates Th17-driven Asthma in Mice.

Microbial maturation disrupted by early-life dysbiosis has been linked with increased asthma risk and severity; however, the immunological mechanisms underpinning this connection are poorly understood. We sought to understand how delaying microbial maturation drives worsened asthma outcomes later in life and its long-term durability. Drinking water was supplemented with antibiotics on Postnatal Days 10-20. To assess the immediate and long-term effects of delaying microbial maturation on experimental asthma, we initiated house dust mite exposure when bacterial diversity was either at a minimum or had recovered. Airway hyperresponsiveness, histology, pulmonary leukocyte recruitment, flow cytometric analysis of cytokine-producing lymphocytes, and assessment of serum IgG1 (Immunoglobulin G1) and IgE (Immunoglobulin E) concentrations were performed. RT-PCR was used to measure IL-13 (Interleukin 13)-induced gene expression in sequentially sorted mesenchymal, epithelial, endothelial, and leukocyte cell populations from the lung. Delayed microbial maturation increased allergen-driven airway hyperresponsiveness and Th17 frequency compared with allergen-exposed control mice, even when allergen exposure began after bacterial diversity recovered. Blockade of IL-17A (Interleukin 17A) reversed the airway hyperresponsiveness phenotype. In addition, allergen exposure in animals that experienced delayed microbial maturation showed signs of synergistic signaling between IL-13 and IL-17A in the pulmonary mesenchymal compartment. Delaying microbial maturation in neonates promotes the development of more severe asthma by increasing Th17 frequency, even if allergen exposure is initiated weeks after microbial diversity is normalized. In addition, IL-17A-aggravated asthma is associated with increased expression of IL-13-induced genes in mesenchymal, but not epithelial cells.

Comparison of Short and Long-Term Results after Injection Laryngoplasty with Radiesse® Voice and Thyroplasty Type I in Unilateral Vocal Fold Palsy.

OBJECTIVES: Unilateral vocal fold palsy independently of etiology results in glottic insufficiency leading to unfavorable short or long-term impact on voice quality. Our aim was to evaluate the effect of injection laryngoplasty using Radiesse® Voice and thyroplasty type I on glottic closure, voice quality and aerodynamics by comparing preoperative, short- and long-term results. MATERIALS AND METHODS: Data of 32 consent patients were reviewed between 2012 and 2023. All patients underwent either injection laryngoplasty (14 patients) or thyroplasty type I (18 patients) under local anesthesia. Maximum phonation time, glottic closure based on videolaryngostroboscopy, VHI-30 values and GRBAS scale were recorded prior, short-term (3 month) and long-term (12 months) after procedures for statistical comparison. Friedman test, Mann-Whitney test and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: In injection laryngoplasty group, we found significant improvement in maximum phonation time (p = 0.002), grade of hoarseness (p = 0.002) and breathiness (p = 0.000) when comparing results before and short-term after procedure. In thyroplasty type I group we saw significant improvement of maximum phonation time (p = 0.000), glottic insufficiency (p = 0.000), all three VHI-30 components (p = 0.000), as well as grade of hoarseness, breathiness (both p = 0.000) and roughness (p = 0.011) of GRBAS scale when comparing voice outcome before and short-term after procedure. There was no significant difference in voice outcome results neither between short and long-term results nor between the two groups in any parameter. CONCLUSION: These results demonstrate both short and long-term efficiency of injection laryngoplasty and thyroplasty type I in the improvement of voice quality and glottic closure.

New computational fluid dynamics-based method for morphological and functional assessment in cardiovascular skill training.

Objective: During cardiovascular surgical skill training, the direct quantification regarding surgical performance is still lacking, including transferring clinically relevant information. Methods: We introduced a novel computational fluid dynamics-based method in support of vascular surgical hands-on training, which applies continuous self-assessment in vascular anastomoses. The validation of the methodology was implemented in comparing with conventional training courses. Results: The fifth and seventh consecutive anastomoses of the experimental group showed significantly improved results regarding anastomosis quality when compared with the control group. Conclusions: Consecutive demonstration of three-dimensional morphology and functional assessment of anastomoses results in improved practical performance among learners regarding anastomosis quality.

Therapeutic effects of Fc gamma RIV inhibition are mediated by selectively blocking immune complex-induced neutrophil activation in epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune bullous disease caused by autoantibodies targeting type VII collagen (COL7). It is characterized by inflammation and subepidermal blistering mainly through immune complex (IC)-mediated activation of neutrophils. In experimental EBA, binding of neutrophils to ICs in the skin and induction of clinical disease depends on the expression of the Fc gamma receptor (FcγR) IV. As activating FcγR mediate both neutrophil extravasation and activation, we used multiphoton imaging to obtain further insights into the mechanistic contribution of FcγRIV in the pathogenesis of EBA. First, we demonstrated that blocking FcγRIV function completely protects LysM-eGFP mice against induction of antibody transfer-induced EBA. To visualize the interactions of anti-COL7 IgG and neutrophils in vivo, fluorescently labeled anti-COL7 IgG was injected into LysM-eGFP mice. Multiphoton microscopy was sequentially performed over a period of 8 days. At all time points, we observed a significantly higher extravasation of neutrophils into the skin of mice treated with anti-FcγRIV antibody compared to controls. However, the percentage of detected neutrophils localized to the target antigen along the dermal-epidermal junction was comparable between both groups. Additionally, reactive oxygen release and migration in vitro assay data demonstrate that FcγRIV antibody treatment inhibits the activation, but not the migration, of neutrophils. Our findings underscore the importance of advanced in vivo imaging techniques to understand the complexity of IC-mediated neutrophil-dependent inflammation, and indicate that the therapeutic utility of FcγRIV blockade is achieved through impairment of IC-mediated neutrophil activation.

Mutual influence between language and perception in multi-agent communication games.

Language interfaces with many other cognitive domains. This paper explores how interactions at these interfaces can be studied with deep learning methods, focusing on the relation between language emergence and visual perception. To model the emergence of language, a sender and a receiver agent are trained on a reference game. The agents are implemented as deep neural networks, with dedicated vision and language modules. Motivated by the mutual influence between language and perception in cognition, we apply systematic manipulations to the agents' (i) visual representations, to analyze the effects on emergent communication, and (ii) communication protocols, to analyze the effects on visual representations. Our analyses show that perceptual biases shape semantic categorization and communicative content. Conversely, if the communication protocol partitions object space along certain attributes, agents learn to represent visual information about these attributes more accurately, and the representations of communication partners align. Finally, an evolutionary analysis suggests that visual representations may be shaped in part to facilitate the communication of environmentally relevant distinctions. Aside from accounting for co-adaptation effects between language and perception, our results point out ways to modulate and improve visual representation learning and emergent communication in artificial agents.

Evidence for the embodiment of the automatic approach bias.

Tendencies of approach and avoidance seem to be a universal characteristic of humans. Specifically, individuals are faster in avoiding than in approaching negative stimuli and they are faster in approaching than in avoiding positive stimuli. The existence of this automatic approach-avoidance bias has been demonstrated in many studies. Furthermore, this bias is thought to play a key role in psychiatric disorders like drug addiction and phobias. However, its mechanisms are far from clear. Theories of embodied cognition postulate that the nature of gestures plays a key role in this process. To shed light on the role of the involved gesture we employed a 2 × 2 factorial design with two types of stimuli. Participants had either to approach positive and avoid negative stimuli (congruent conditions) or to avoid positive stimuli and approach negative stimuli (incongruent conditions). Further, they responded either with a joystick or a button press on a response pad. Participants reacted faster in congruent conditions, i.e., avoiding negative stimuli and approaching positive stimuli, than in incongruent conditions. This replicates the known approach and avoidance bias. However, direct analysis of the button press condition revealed no reaction time advantage for congruent trials compared to incongruent trials. In contrast, in the joystick condition participants were significantly faster performing congruent reactions than incongruent reactions. This interaction, a significant reaction time advantage, when the response is enacted by moving a joystick towards or away from the body provides evidence that approach-avoidance tendencies have a crucial bodily component.

Analysis of pharmacovigilance databases for spontaneous reports of adverse drug reactions related to substandard and falsified medical products: A descriptive study.

Introduction: The public health threat of substandard and falsified medicines has been well known in the last two decades, and several studies focusing on the identification of products affected and preventing consumption have been published. However, the number of these products reaching patients and causing health consequences and adverse drug reactions is not a well-researched area. Objectives: Our aim was to identify and describe the characteristics of cases that are related to adverse drug reactions potentially originating from counterfeit medication using publicly available pharmacovigilance data. Methods: A descriptive study was performed based on pharmacovigilance data retrieved from Individual Case Safety Reports (ICSRs) identified in the European Medicines Agency's EudraVigilance and FDA Adverse Event Reporting System (FAERS) databases in April 2022 using selected MedDRA preferred terms: counterfeit product administered, product counterfeit, product label counterfeit, product packaging counterfeit, suspected counterfeit product, adulterated product, product tampering, and suspected product tampering. ICSRs were analyzed by age and gender, by year of reporting, region of origin, reporter's profession, and severity of the outcome. The disproportionality method was used to calculate pharmacovigilance signal measures. Results: A total of 5,253 cases in the FAERS and 1,049 cases in the EudraVigilance database were identified, generally affecting middle-aged men with a mean age of 51.055 (±19.62) in the FAERS and 64.18% of the cases between 18 and 65 years, while the male to female ratios were 1.18 and 1.5. In the FAERS database, we identified 138 signals with 95% confidence interval including sildenafil (n = 314; PRR, 12.99; ROR, 13.04; RRR, 11.97), tadalafil (n = 200; PRR, 11.51; ROR, 11.55; RRR, 10.94), and oxycodone (n = 190; PRR, 2.47; ROR, 2.14; RRR, 2.47). While in the EV data 31, led by vardenafil (n = 16, PRR = 167.19; 101.71-274.84; 95% CI, RRR = 164.66; 100.17-270.66; 95% CI, ROR = 169.47; 103.09-278.60; 95% CI, p < 0.001), entecavir (n = 46, PRR = 161.26, RRR = 154.24, ROR = 163.32, p < 0.001), and tenofovir (n = 20, PRR = 142.10, RRR = 139.42, ROR = 143.74, p < 0.001). Conclusion: The application of pharmacovigilance datasets to identify potential counterfeit medicine ADRs can be a valuable tool in recognition of potential risk groups of consumers and the affected active pharmaceutical ingredients and products. However, the further development and standardization of ADR reporting, pharmacovigilance database analysis, and prospective and real-time collection of potential patients with health consequences are warranted in the future.

WildLab: A naturalistic free viewing experiment reveals previously unknown electroencephalography signatures of face processing.

Neural mechanisms of face perception are predominantly studied in well-controlled experimental settings that involve random stimulus sequences and fixed eye positions. Although powerful, the employed paradigms are far from what constitutes natural vision. Here, we demonstrate the feasibility of ecologically more valid experimental paradigms using natural viewing behaviour, by combining a free viewing paradigm on natural scenes, free of photographer bias, with advanced data processing techniques that correct for overlap effects and co-varying non-linear dependencies of multiple eye movement parameters. We validate this approach by replicating classic N170 effects in neural responses, triggered by fixation onsets (fixation event-related potentials [fERPs]). Importantly, besides finding a strong correlation between both experiments, our more natural stimulus paradigm yielded smaller variability between subjects than the classic setup. Moving beyond classic temporal and spatial effect locations, our experiment furthermore revealed previously unknown signatures of face processing: This includes category-specific modulation of the event-related potential (ERP)'s amplitude even before fixation onset, as well as adaptation effects across subsequent fixations depending on their history.

Intravital imaging of mucus transport in asthmatic mice using microscopic optical coherence tomography.

Asthma is one of the most common chronic diseases. Mucus overproduction is consistently linked to asthma morbidity and mortality. Despite the knowledge of the importance of mucus, little data exist on how mucus is transported in asthma and the immediate effects of therapeutic intervention. We therefore used microscopic optical coherence tomography (mOCT) to study spontaneous and induced mucus transport in an interleukin-13 (IL-13)-induced asthma mouse model and examined the effects of isotonic (0.9% NaCl) and hypertonic saline (7% NaCl), which are used to induce mucus transport in cystic fibrosis. Without intervention, no bulk mucus transport was observed by mOCT and no intraluminal mucus was detectable in the intrapulmonary airways by histology. Administration of ATP-γ-S induced mucus secretion into the airway lumen, but it did not result in bulk mucus transport in the trachea. Intraluminal-secreted immobile mucus could be mobilized by administration of isotonic or hypertonic saline but hypertonic saline mobilized mucus more reliably than isotonic saline. Irrespective of saline concentration, the mucus was transported in mucus chunks. In contrast to isotonic saline solution, hypertonic saline solution alone was able to induce mucus secretion. In conclusion, mOCT is suitable to examine the effects of mucus-mobilizing therapies in vivo. Although hypertonic saline was more efficient in inducing mucus transport, it induced mucus secretion, which might explain its limited benefit in patients with asthma.

Competencies and needs of nurse educators and clinical mentors for teaching in the digital age - a multi-institutional, cross-sectional study.

BACKGROUND: The impact of technology and digitalization on health care systems will transform the nursing profession worldwide. Nurses need digital competencies to integrate new technology in their professional activities. Nurse educators play a crucial role in promoting the acquisition of digital competences and therefore need to be digitally competent themselves. Research on digital competencies of nursing educators is scarce but suggests lack of digital knowledge and skills and support needs. Although digitalization is to be seen as a global process, regional contexts need to be taken into account, such as pre-existing competencies, local conditions, and individual needs. Thus, it remains unclear which competencies nurse educators possess and which support needs they have. Aim of this study was to assess nurse educators' and clinical mentors' digital competencies and explore their needs and requirements concerning the digital aspects of their pedagogy and teaching activities in Germany. METHODS: A descriptive exploratory study with a cross-sectional design was conducted. Participants were identified using a convenience sampling approach. Data were collected during July and September 2020 using a standardized self-reported questionnaire that was developed specifically for this study. The questionnaire was provided in a paper and online format and participants could decide which format to use. It contained open- and closed-ended questions. Data were analyzed using descriptive and content analysis. Additionally, explorative subgroup analyses based on job designation, age, and gender were performed. Reporting of this study adhered to the STROBE checklist. RESULTS: A total of 169 educating nurses participated in the survey. The respondents considered themselves as digitally competent and showed a positive attitude towards the integration of digital technology in their teaching activities. Their perceived preparedness to integrate digital technology into teaching and training varied. Almost all respondents (98%) declared a need for further training and seemed motivated to participate in corresponding educational events. There were some indications for differences in competencies or needs between subgroups. CONCLUSIONS: Educating nurses appear to possess basic digital competencies but there is a need to support their professional development in terms of new technologies. Findings can be used as a basis for developing supportive interventions. Further qualitative investigations could inform the design and content of such interventions.