Prediction of sensorimotor contingencies generates saccadic omission.

With every movement of our eyes, the visual receptors in the retina are swiped across the visual scene. Saccades are the fastest and most frequent movements we perform, yet we remain unaware of the self-produced visual motion. Previous research has tried to identify a dedicated suppression mechanism that either actively or passively cancels vision at the time of saccades.1 Here, we investigated a novel theory, which states that saccadic omission results from habituation to the predicted sensory consequences of our own actions. We experimentally induced novel, i.e., artificial visual consequences of saccade performance by presenting gratings that were drifting faster than the flicker fusion frequency and that became visible only when participants performed saccades. We asked participants to perform more than 100 saccades in each session across these gratings to make the novel contingencies predictable for the sensorimotor system. We found that contrast sensitivity for intra-saccadic motion declined drastically after repeated exposure of such motion. The reduction in sensitivity was even specific to the saccade vector performed in habituation trials. Moreover, when subjects performed the same task in fixation, no reduction in sensitivity was observed. In a motion speed comparison task, we found that the reduction in contrast sensitivity is the consequence of silencing-predicted intra-saccadic visual motion. Our data demonstrate that the sensorimotor system selectively habituates to recurring intra-saccadic visual motion, suggesting an efficient prediction mechanism of visual stability.

Motor variability modulates calibration of precisely timed movements.

Interacting with the environment often requires precisely timed movements, challenging the brain to minimize the detrimental impact of neural noise. Recent research demonstrates that the brain exploits the variability of its temporal estimates and recalibrates perception accordingly. Time-critical movements, however, contain a sensory measurement and a motor stage. The brain must have knowledge of both in order to avoid maladapted behavior. By manipulating sensory and motor variability, we show that the sensorimotor system recalibrates sensory and motor uncertainty separately. Serial dependencies between observed interval durations in the previous and motor reproductions in the current trial were weighted by the variability of movements. These serial dependencies generalized across different effectors, but not to a visual discrimination task. Our results suggest that the brain has accurate knowledge about contributions of motor uncertainty to errors in temporal movements. This knowledge about motor uncertainty seems to be processed separately from knowledge about sensory uncertainty.

Four decades of experience of prosthetic valve endocarditis reflect a high variety of diverse pathogens.

Prosthetic valve endocarditis (PVE) remains a serious condition with a high mortality rate. Precise identification of the PVE-associated pathogen/s and their virulence is essential for successful therapy and patient survival. The commonly described PVE-associated pathogens are staphylococci, streptococci, and enterococci, with Staphylococcus aureus being the most frequently diagnosed species. Furthermore, multi-drug resistance pathogens are increasing in prevalence and continue to pose new challenges mandating a personalized approach. Blood cultures in combination with echocardiography are the most common methods to diagnose PVE, often being the only indication, it exists. In many cases, the diagnostic strategy recommended in the clinical guidelines does not identify the precise microbial agent, and frequently, false-negative blood cultures are reported. Despite the fact that blood culture findings are not always a good indicator of the actual PVE agent in the valve tissue, only a minority of re-operated prostheses are subjected to microbiological diagnostic evaluation. In this review, we focus on the diversity and the complete spectrum of PVE-associated bacterial, fungal, and viral pathogens in blood and prosthetic heart valve, their possible virulence potential, and their challenges in making a microbial diagnosis. We are curious to understand if the unacceptable high mortality of PVE is associated with the high number of negative microbial findings in connection with a possible PVE. Herein, we discuss the possibilities and limits of the diagnostic methods conventionally used and make recommendations for enhanced pathogen identification. We also show possible virulence factors of the most common PVE-associated pathogens and their clinical effects. Based on blood culture, molecular biological diagnostics, and specific valve examination, better derivations for the antibiotic therapy as well as possible preventive intervention can be established in the future.

Increased scene complexity during free visual exploration reveals residual unilateral neglect in recovered stroke patients.

Unilateral neglect is a common cognitive syndrome after stroke, which is defined as a spatially specific unawareness of the contralesional space. The syndrome is caused by disruptions of attentional networks in the brain, which impair the patients' ability to direct attention towards the contralesional space. During recovery, patients often learn to compensate by voluntarily directing their attention to the neglected side at the expense of cognitive resources. In this study, we examined the impact of the complexity of visual input on free visual exploration behavior of unilateral neglect and apparently recovered patients. We asked whether increasing scene complexity would allow the detection of residual unilateral neglect in recovered patients by increasing the amount of cognitive resources needed for visual processing and limiting capacities for compensation. Using virtual reality, we analyzed the spatial distribution of gaze of unilateral neglect patients, patients who had, according to conventional diagnostics, recovered from the syndrome, stroke patients with no history of unilateral neglect, and age-matched healthy controls. We manipulated the complexity of an immersive virtual scene presented on head mounted displays. We identified the orientation bias towards the ipsilesional side as a sensitive and specific marker of unilateral neglect, which was present in unilateral neglect and recovered patients but absent in stroke patients with no history of unilateral neglect and controls. Increasing scene complexity exacerbated the orientation shift in unilateral neglect patients and revealed that three out of nine (33%) recovered patients had a high probability of suffering from residual unilateral neglect as estimated by a generalized linear model using the median horizontal gaze position as a predictor.

Addendum: Implicit learning of temporal behavior in complex dynamic environments.

New analyses of the data in this study (Salet et al., 2021, Psychonomic Bulletin & Review, https://doi.org/10.3758/s13423-020-01873-x ) have led us to reinterpret our main finding. Previously, we had attributed better performance for targets appearing at regular intervals versus irregular intervals to "temporal statistical learning." That is, we surmised that this benefit for the regular intervals arises because participants implicitly distilled the regular 3000 ms interval from the otherwise variable environment (i.e., irregular intervals) to predict future (regular) targets. The analyses presented in this Addendum, however, show that this benefit can be attributed to ongoing "temporal preparation" rather than temporal statistical learning.

Surgery for Aortic Prosthetic Valve Endocarditis in the Transcatheter Era.

Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6-62.0) v/s 45.4 (32.6-58.1), p = 0.207) and STS-PROM (1.8 (1.6-2.1) v/s 1.9 (1.4-2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort.

Temporal perturbations cause movement-context independent but modality specific sensorimotor adaptation.

Complex, goal-directed and time-critical movements require the processing of temporal features in sensory information as well as the fine-tuned temporal interplay of several effectors. Temporal estimates used to produce such behavior may thus be obtained through perceptual or motor processes. To disentangle the two options, we tested whether adaptation to a temporal perturbation in an interval reproduction task transfers to interval reproduction tasks with varying sensory information (visual appearance of targets, modality, and virtual reality [VR] environment or real-world) or varying movement types (continuous arm movements or brief clicking movements). Halfway through the experiments we introduced a temporal perturbation, such that continuous pointing movements were artificially slowed down in VR, causing participants to adapt their behavior to sustain performance. In four experiments, we found that sensorimotor adaptation to temporal perturbations is independent of environment context and movement type, but modality specific. Our findings suggest that motor errors induced by temporal sensorimotor adaptation affect the modality specific perceptual processing of temporal estimates.

Gastric Mucosal Devitalization (GMD): Using the Porcine Model to Develop a Novel Endoscopic Bariatric Approach.

BACKGROUND AND AIMS: As the pig model has similar gastrointestinal anatomy and physiology to humans, we used pigs to create a gastric mucosal devitalization (GMD) model in preparation for clinical translation of this technique as an endoscopic bariatric therapy (EBT). The aims of this study were to determine the ablation parameters and technique for a successful, safe, and feasible large surface area GMD that produces weight loss. METHODS: We performed GMD using argon plasma coagulation (APC) in 3 phases. Phase 1 assessed the ablation energy required to accomplish selective mucosal ablation using ex vivo pig stomachs (n = 2). Phase 2 assessed the optimal percentage of mucosal surface area to be treated and was performed on 10 pigs. Phase 3 assessed feasibility, efficacy, and safety with 8 pigs randomized into GMD (n = 4) or sham (SH, n = 4) and survived for 1 month. Body weights (GMD, n = 4, SH, n = 4) were measured daily in phase 3 for 1 month, and relative body weights were calculated and analyzed using one-tailed Student's t-test. Percent body fat was compared between GMD and SH at baseline and 1 month post-GMD. RESULTS: Phase 1 identified the optimal ablation parameters (120 W) that were then used in phase 2. Phase 2 revealed a trend that was suggestive that the optimal percent surface area to ablate was similar to that which is removed at laparoscopic sleeve gastrectomy. In phase 3, GMD was performed over 70% surface area of the greater curvature of the stomach in four pigs. GMD pigs had significantly lower relative body weight increase compared to SH at 1 month (1.375 ± 0.085 vs 1.575 ± 0.047, p = 0.0435). MRI showed a significantly lower body fat mass at 1 month in GMD pigs (5.9 ± 0.4% vs 12.7 ± 2.3%, p = 0.026) compared to SH. CONCLUSIONS: GMD resulted in decreased weight gain in the GMD group as evidenced by a lower relative body weight at 1 month. GMD in an animal model appears to show promise as a potential weight loss therapy.

Temporal Context Actively Shapes EEG Signatures of Time Perception.

Our subjective perception of time is optimized to temporal regularities in the environment. This is illustrated by the central tendency effect: When estimating a range of intervals, short intervals are overestimated, whereas long intervals are underestimated to reduce the overall estimation error. Most models of interval timing ascribe this effect to the weighting of the current interval with previous memory traces after the interval has been perceived. Alternatively, the perception of the duration could already be flexibly tuned to its temporal context. We investigated this hypothesis using an interval reproduction task in which human participants (both sexes) reproduced a shorter and longer interval range. As expected, reproductions were biased toward the subjective mean of each presented range. EEG analyses showed that temporal context indeed affected neural dynamics during the perception phase. Specifically, longer previous durations decreased contingent negative variation and P2 amplitude and increased beta power. In addition, multivariate pattern analysis showed that it is possible to decode context from the transient EEG signal quickly after both onset and offset of the perception phase. Together, these results suggest that temporal context creates dynamic expectations which actively affect the perception of duration.SIGNIFICANCE STATEMENT The subjective sense of duration does not arise in isolation, but is informed by previous experiences. This is demonstrated by abundant evidence showing that the production of duration estimates is biased toward previously experienced time intervals. However, it is yet unknown whether this temporal context actively affects perception or only asserts its influence in later, postperceptual stages as proposed by most current formal models of this task. Using an interval reproduction task, we show that EEG signatures flexibly adapt to the temporal context during perceptual encoding. Furthermore, interval history can be decoded from the transient EEG signal even when the current duration was identical. Thus, our results demonstrate that context actively influences perception.

Performance-informed EEG analysis reveals mixed evidence for EEG signatures unique to the processing of time.

Certain EEG components (e.g., the contingent negative variation, CNV, or beta oscillations) have been linked to the perception of temporal magnitudes specifically. However, it is as of yet unclear whether these EEG components are really unique to time perception or reflect the perception of magnitudes in general. In the current study we recorded EEG while participants had to make judgments about duration (time condition) or numerosity (number condition) in a comparison task. This design allowed us to directly compare EEG signals between the processing of time and number. Stimuli consisted of a series of blue dots appearing and disappearing dynamically on a black screen. Each stimulus was characterized by its duration and the total number of dots that it consisted of. Because it is known that tasks like these elicit perceptual interference effects that we used a maximum-likelihood estimation (MLE) procedure to determine, for each participant and dimension separately, to what extent time and numerosity information were taken into account when making a judgement in an extensive post hoc analysis. This approach enabled us to capture individual differences in behavioral performance and, based on the MLE estimates, to select a subset of participants who suppressed task-irrelevant information. Even for this subset of participants, who showed no or only small interference effects and thus were thought to truly process temporal information in the time condition and numerosity information in the number condition, we found CNV patterns in the time-domain EEG signals for both tasks that was more pronounced in the time-task. We found no substantial evidence for differences between the processing of temporal and numerical information in the time-frequency domain.

Quantification of Multiple Bacteria in Calcified Structural Valvular Heart Disease.

Genome studies of heart valve tissue (HVT) in patients with structural valvular heart disease (sVHD) and acute infective endocarditis (aIE) showed polymicrobial infections. Subject of this study is the quantification of bacterial DNA in HVT of sVHD in comparison to aIE. It will be examined whether the bacterial DNA concentration can be used as surrogate marker to differentiate chronic and acute infections. DNA was isolated from HVT of 100 patients with sVHD and 23 microbiologically positively tested patients with aIE. Selected pathogens (Cutibacterium acnes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Clostridium difficile, and Klebsiella pneumoniae) were quantified using TaqMan-qPCR. Polymicrobial infiltration of HVT was investigated by immunohistologic methods. Of 100 sVHD patients, 94 tested positive for bacteria by 16S-rDNA and 72 by TaqMan-qPCR. In 29% of the sVHD cohort and in 70% of the aIE cohort, a coinfection with more than 2 bacteria was observed as indication of a polymicrobial infection. The most common pathogens in the sVHD patients were C. acnes (59%; 5-4074 pg/mL), E. faecalis (16%, 174-2781 pg/mL), and S. aureus (15%, 8-105 pg/mL). The DNA concentration of E. faecalis (P = 0.0285) and S. aureus (P = 0.0149) is significantly lower in the sVHD cohort than in the aIE cohort. sVHD is associated with bacterial infection and infiltration of the HVT in a majority of cases. TaqMan-qPCR is a valid instrument for the specific detection of bacteria in HVT and allows discrimination between sVHD and aIE for E. faecalis and S. aureus.

Bacterial infiltration in structural heart valve disease.

OBJECTIVES: The pathology of structural valvular heart disease (sVHD) ranges from basic diseases of rheumatologic origin to chronic degenerative remodeling processes after acute bacterial infections. Molecular genetic methods allow detection of the complete microbial spectrum in heart valve tissues independent of microbiological cultivation. In particular, whole-metagenome analysis is a sensitive and highly specific analytical method that allows a deeper insight into the pathogenicity of the diseases. In the present study we assessed the pathogen spectrum in heart valve tissue from 25 sVHD patients using molecular and microbiological methods. METHODS: Twenty-five sVHD patients were selected randomly from an observational cohort study (March 2016 to January 2017). The explanted native heart valves were examined using microbiological methods and immunohistological structural analysis. In addition, the bacterial metagenome of the heart valve tissue was determined using next-generation sequencing. RESULTS: The use of sonication as a pretreatment of valve tissue from 4 sVHD patients permitted successful detection of Clostridium difficile, Enterococcus faecalis, Staphylococcus saccharolyticus, and Staphylococcus haemolyticus using microbial cultivation. Histological staining revealed intramural localization. Metagenome analysis identified a higher rate of bacterial infiltration in 52% of cases. The pathogen spectrum included both gram-positive and gram-negative bacteria. CONCLUSIONS: Microbiological and molecular biological studies are necessary to detect the spectrum of bacteria in a calcified heart valve. Metagenome analysis is a valid method to gain new insight into the polymicrobial pathophysiology of sVHD. Our results suggest that an undetected proportion of sVHD might be triggered by chronic inflammation or influenced by secondary bacterial infiltration.

Gastric mucosal devitalization improves blood pressure, renin and cardiovascular lipid deposition in a rat model of obesity.

Background and study aims In lieu of the drawbacks of metabolic surgery, a method of mimicking resection of the gastric mucosa could be of value to those with obesity-related cardiovascular disease (CVD). Our study aims to investigate the effect of gastric mucosal devitalization (GMD) on blood pressure (BP) and cardiovascular lipid deposition in a rat model of obesity. Methods GMD of 70 % of the stomach was achieved by argon plasma coagulation. GMD was compared to sleeve gastrectomy (SG) and sham (SH) in a high-fat-diet-induced rat model of obesity (48 rats). At 8 weeks, we measured noninvasive BP, renin, vessel relaxation and ghrelin receptor regulation in the aorta. In addition, we quantified cardiac lipid deposition and lipid droplet deposition in cardiac muscle and aorta. Results GMD and SG were observed to have similar reductions in body weight, visceral adiposity, and serum lipid profile compared to SH rats. GMD resulted in a significant reduction in arterial BP compared to SH. Furthermore, there were significant reductions in plasma renin activity and percentage of phenylnephrine constriction to acetylcholine at the aortic ring in GMD rats compared to SH, providing insights into the mechanisms behind the reduced BP. Interestingly, the reduced BP occurred despite a reduction in endothelial ghrelin recteptor activation. Cardiac lipid content was significantly reduced in GMD rats. Lipid deposition, as illustrated by Nile Red stain, was reduced in cardiac muscle and the aorta. Conclusion GMD resulted in a significant improvement in BP, renin and cardiovascular lipid deposition. GMD deserves further attention as a method of treating obesity-related CVD.

Eliciting contextual temporal calibration: The effect of bottom-up and top-down information in reproduction tasks.

Bayesian integration assumes that a current observation is integrated with previous observations. An example in the temporal domain is the central tendency effect: when a range of durations is presented, a regression towards the mean is observed. Furthermore, a context effect emerges if a partially overlapping lower and a higher range of durations is presented in a blocked design, with the overlapping durations pulled towards the mean duration of the block. We determine under which conditions this context effect is observed, and whether explicit cues strengthen the effect. Each block contained either two or three durations, with one duration present in both blocks. We provided either no information at the start of each block about the nature of that block, provided written ("short" / "long" or "A" / "B") categorizations, or operationalized pitch (low vs high) to reflect the temporal context. We demonstrate that (1) the context effect emerges as long as sufficiently distinct durations are presented; (2) the effect is not modulated by explicit instructions or other cues; (3) just a single additional duration is sufficient to produce a context effect. Taken together, these results provide information on the most efficient operationalization to evoke the context effect, allowing for highly economical experimental designs, and highlights the automaticity by which priors are constructed.

Robustness of individual differences in temporal interference effects.

Magnitudes or quantities of the different dimensions that define a stimulus (e.g., space, speed or numerosity) influence the perceived duration of that stimulus, a phenomenon known as (temporal) interference effects. This complicates studying the neurobiological foundation of the perception of time, as any signatures of temporal processing are tainted by interfering dimensions. In earlier work, in which judgements on either time or numerosity were made while EEG was recorded, we used Maximum Likelihood Estimation (MLE) to estimate, for each participant separately, the influence of temporal and numerical information on making duration or numerosity judgements. We found large individual differences in the estimated magnitudes, but ML-estimates allowed us to partial out interference effects. However, for such analyses, it is essential that estimates are meaningful and stable. Therefore, in the current study, we examined the reliability of the MLE procedure by comparing the interference magnitudes estimated in two sessions, spread a week apart. In addition to the standard paradigm, we also presented task variants in which the interfering dimension was manipulated, to assess which aspects of the numerosity dimension exert the largest influence on temporal processing. The results indicate that individual interference magnitudes are stable, both between sessions and over tasks. Further, the ML-estimates of the time-numerosity judgement tasks were predictive of performance in a standard temporal judgement task. Thus, how much temporal information participants use in time estimations tasks seems to be a stable trait that can be captured with the MLE procedure. ML-estimates are, however, not predictive of performance in other interference-tasks, here operationalized by a numerical Stroop task. Taken together, the MLE procedure is a reliable tool to quantify individual differences in magnitude interference effects and can therefore reliably inform the analysis of neuroimaging data when contrasts are needed between the accumulation of a temporal and an interfering dimension.

Gastric mucosal devitalization is safe and effective in reducing body weight and visceral adiposity in a porcine model.

BACKGROUND AND AIMS: The early improvement in metabolic profile after sleeve gastrectomy (SG) indicates that the significant benefits of metabolic surgery are gastric in origin. We have previously demonstrated that devitalization of the gastric mucosa (without a reduction in gastric volume) in metabolically disturbed obese rats results in an improvement of obesity and its associated comorbidities. The aims of this study were to assess the technical feasibility, efficacy, and safety of gastric mucosal devitalization (GMD) in a large animal (porcine) model. METHODS: A 3-arm (GMD versus SG versus sham [SH]) prospective randomized controlled trial with an 8-week follow-up period was performed. The primary endpoint was relative weight loss. Secondary endpoints were absolute body weight, abdominal visceral adiposity, abdominal subcutaneous adiposity, organ lipid content, and serum ghrelin level. RESULTS: GMD resulted in a significant relative weight loss of 36% over SH at 8 weeks (P < .05). There was no significant difference in relative weight loss between GMD and SG at 4 weeks; however, SG resulted in a 29% superior relative weight loss at 8 weeks (P < .05). With regard to visceral adiposity, there was a significant benefit of GMD over SH at 8 weeks. Despite differences in relative weight loss, there was no significant difference in visceral adiposity between SG and GMD at 8 weeks. Significant improvements in GMD over SH were noted with regard to skeletal and heart muscle lipid content. GMD pigs at 8 weeks demonstrated regeneration of the gastric mucosa without ulceration or significant scarring. Despite mucosal regeneration, the abundance of serum ghrelin was significantly lower in the GMD cohort compared with the SG and SH cohorts. CONCLUSIONS: GMD was technically feasible and resulted in relative weight loss and an improvement in visceral adiposity. The benefits noted were out of proportion to what would be expected with weight loss alone.

Gastric mucosal devitalization reduces adiposity and improves lipid and glucose metabolism in obese rats.

BACKGROUND AND AIMS: The gastric mucosa is an endocrine organ that regulates satiation pathways by expression of orexigenic and anorexigenic hormones. Vertical sleeve gastrectomy (VSG) excludes gastric mucosa and reduces gastric volume. Our study aimed to investigate the independent effects of altering gastric mucosa on obesity and its related comorbidities. METHODS: Gastric mucosa devitalization (GMD) of 70% of the stomach was achieved by argon plasma coagulation in a high-fat diet rat model and was compared with VSG and sham surgery. In an 8-week follow-up study, we quantified body weight, visceral adiposity, insulin resistance index, cholesterol profiles, and free fatty acid profiles by enzyme-linked immunosorbent assay (ELISA). Following a 2-hour oral glucose tolerance test, the kinetics of ghrelin, glucagon-like peptide-1, peptide YY, and serum and liver bile acid levels were measured. Liver lipid content was quantified by ELISA. RESULTS: GMD resulted in significant reductions in body weight, visceral and subcutaneous adipose tissue, and hepatic steatosis as well as an improvement in lipid metabolism. GMD resulted in significant reductions in food intake and intestinal malabsorption of free fatty acids, both contributing to improved body composition and metabolic profile. Mechanistically, GMD resulted in a significant reduction in serum palmitate levels as well as an increase in serum and liver bile acid levels, known to alter glucose and lipid metabolism. Similar changes were noted when VSG rats were compared with sham surgery rats. CONCLUSIONS: Devitalization of gastric mucosa, independent of altering gastric volume, was able to reduce obesity-related comorbidities. The gastric mucosa may be a potential target for treating obesity and its associated comorbidities.

Temporal Context Influences the Perceived Duration of Everyday Actions: Assessing the Ecological Validity of Lab-Based Timing Phenomena.

Timing is key to accurate performance, for example when learning a new complex sequence by mimicry. However, most timing research utilizes artificial tasks and simple stimuli with clearly marked onset and offset cues. Here we address the question whether existing interval timing findings generalize to real-world timing tasks. In this study, animated video clips of a person performing different everyday actions were presented and participants had to reproduce the main action's duration. Although reproduced durations are more variable then observed in laboratory studies, the data adheres to two interval timing laws: Relative timing sensitivity is constant across durations (scalar property), and the subjective duration of a previous action influenced the current action's perceived duration (temporal context effect). Taken together, this demonstrates that laboratory findings generalize, and paves the way for studying interval timing as a component of complex, everyday cognitive performance.

The oral microbiome-the relevant reservoir for acute pediatric appendicitis?

PURPOSE: The oral microbiome has been related to numerous extra oral diseases. Recent studies detected a high abundance of oral bacteria in inflamed appendices in pediatric patients. To elucidate the role of oral bacteria in acute pediatric appendicitis, we studied the oral and appendiceal microbiome of affected children compared to healthy controls. METHODS: Between January and June 2015, 21 children undergoing appendectomy for acute appendicitis and 28 healthy controls were prospectively enrolled in the study. All individuals underwent thorough dental examination and laboratory for inflammatory parameters. Samples of inflamed appendices and the gingival sulcus were taken for 16S rDNA sequencing. RT-qPCR of Fusobacterium nucleatum, Peptostreptococcus stomatis, and Eikenella corrodens was performed and their viability was tested under acidic conditions to mimic gastric transfer. RESULTS: In phlegmonous appendices, Bacteroidetes and Porphyromonas were discovered as dominant phylum and genus. In sulcus samples, Firmicutes and Streptococcus were detected predominantly. P. stomatis, E. corrodens, and F. nucleatum were identified in each group. Viable amounts of P. stomatis were increased in sulci of children with acute appendicitis compared to sulci of healthy controls. In inflamed appendices, viable amounts of E. corrodens and F. nucleatum were decreased compared to sulci of children with appendicitis. Postprandial viability could be demonstrated for all tested bacteria. CONCLUSION: In children with acute appendicitis, we identified several oral bacterial pathogens. Based on postprandial viability of selected species, a viable migration from the oral cavity through the stomach to the appendix seems possible. Thus, the oral cavity could be a relevant reservoir for acute appendicitis.

New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis.

AIMS: In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. MATERIAL AND METHODS: Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). RESULTS: Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. CONCLUSION: The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes.