Pacing with restoration of respiratory sinus arrhythmia improved cardiac contractility and the left ventricular output: a translational study

Introduction: Respiratory sinus arrhythmia (RSA) is a prognostic value for patients with heart failure and is defined as a beat-to-beat variation of the timing between the heart beats. Patients with heart failure or patients with permanent cardiac pacing might benefit from restoration of RSA. The aim of this translational, proof-of-principle study was to evaluate the effect of pacing with or without restored RSAon parameters of LV cardiac contractility and the cardiac output

Effect of Ischemic Preconditioning and Postconditioning on Exosome-Rich Fraction microRNA Levels, in Relation with Electrophysiological Parameters and Ventricular Arrhythmia in Experimental Closed-Chest Reperfused Myocardial Infarction

We investigated the antiarrhythmic effects of ischemic preconditioning (IPC) and postconditioning (PostC) by intracardiac electrocardiogram (ECG) and measured circulating microRNAs (miRs) that are related to cardiac conduction. Domestic pigs underwent 90-min. percutaneous occlusion of the mid left anterior coronary artery, followed by reperfusion. The animals were divided into three groups: acute myocardial infarction (AMI, n = 7), ischemic preconditioning-acute myocardial infarction (IPC-AMI) (n = 9), or AMI-PostC (n = 5). IPC was induced by three 5-min. episodes of repetitive ischemia/reperfusion cycles (rI/R) before AMI. PostC was induced by six 30-s rI/R immediately after induction of reperfusion 90 min after occlusion. Before the angiographic procedure, a NOGA endocardial mapping catheter was placed again the distal anterior ventricular endocardium to record the intracardiac electrogram (R-amplitude, ST-Elevation, ST-area under the curve (AUC), QRS width, and corrected QT time (QTc)) during the entire procedure. An arrhythmia score was calculated. Cardiac MRI was performed after one-month. IPC led to significantly lower ST-elevation, heart rate, and arrhythmia score during ischemia. PostC induced a rapid recovery of R-amplitude, decrease in QTc, and lower arrhythmia score during reperfusion. Slightly higher levels of miR-26 and miR-133 were observed in AMI compared to groups IPC-AMI and AMI-PostC. Significantly lower levels of miR-1, miR-208, and miR-328 were measured in the AMI-PostC group as compared to animals in group AMI and IPC-AMI. The arrhythmia score was not significantly associated with miRNA plasma levels. Cardiac MRI showed significantly smaller infarct size in the IPC-AMI group when compared to the AMI and AMI-PostC groups. Thus, IPC led to better left ventricular ejection fraction at one-month and it exerted antiarrhythmic effects during ischemia, whereas PostC exhibited antiarrhythmic properties after reperfusion, with significant downregulaton of ischemia-related miRNAs

Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI

Lower-Level Stimulus Features Strongly Influence Responses in the Fusiform Face Area

An intriguing region of human visual cortex (the fusiform face area; FFA) responds selectively to faces as a general higher-order stimulus category. However, the potential role of lower-order stimulus properties in FFA remains incompletely understood. To clarify those lower-level influences, we measured FFA responses to independent variation in 4 lower-level stimulus dimensions using standardized face stimuli and functional Magnetic Resonance Imaging (fMRI). These dimensions were size, position, contrast, and rotation in depth (viewpoint). We found that FFA responses were strongly influenced by variations in each of these image dimensions; that is, FFA responses were not “invariant” to any of them. Moreover, all FFA response functions were highly correlated with V1 responses (r = 0.95–0.99). As in V1, FFA responses could be accurately modeled as a combination of responses to 1) local contrast plus 2) the cortical magnification factor. In some measurements (e.g., face size or a combinations of multiple cues), the lower-level variations dominated the range of FFA responses. Manipulation of lower-level stimulus parameters could even change the category preference of FFA from “face selective” to “object selective.” Altogether, these results emphasize that a significant portion of the FFA response reflects lower-level visual responses

Towards a Mathematical Theory of Cortical Micro-circuits

The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM), can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model

Memory Influences Visual Cognition across Multiple Functional States of Interactive Cortical Dynamics

No embargo requiredMemory supports a wide range of abilities from categorical perception to goal-directed behavior, such as decision-making and episodic recognition. Memory activates fast and surprisingly accurately and even when information is ambiguous or impoverished (i.e., showing object constancy). This paper proposes the multiple-state interactive (MUSI) account of object cognition that attempts to explain how sensory stimulation activates memory across multiple functional states of neural dynamics, including automatic and strategic mental simulation mechanisms that can ground cognition in modal information processing. A key novel postulate of this account is ‘multiple-function regional activity’: The same neuronal population can contribute to multiple brain states, depending upon the dominant set of inputs at that time. In state 1, the initial fast bottom-up pass through posterior neocortex happens between 95 ms and ~200 ms, with knowledge supporting categorical perception by 120 ms. In state 2, starting around 200 ms, a sustained state of iterative activation of object-sensitive cortex involves bottom-up, recurrent, and feedback interactions with frontoparietal cortex. This supports higher cognitive functions associated with decision-making even under ambiguous or impoverished conditions, phenomenological consciousness, and automatic mental simulation. In the latest state so far identified, state M, starting around 300 to 500 ms, large-scale cortical network interactions, including between multiple networks (e.g., control, salience, and especially default mode), further modulate posterior cortex. This supports elaborated cognition based on earlier processing, including episodic memory, strategic mental simulation, decision evaluation, creativity, and access consciousness. Convergent evidence is reviewed from cognitive neuroscience of object cognition, decision-making, memory, and mental imagery that support this account and define the brain regions and time course of these brain dynamics

Invasive Fungal Infection Caused by Exophiala dermatitidis in a Patient After Lung Transplantation : Case Report and Literature Review

This report describes a case of invasive Exophiala dermatitidis infection after double lung transplantation in a 76-year-old man. After thoracotomy, the patients wound showed dehiscence with purulent secretion. The black yeast was isolated from cultures taken from the wound, and species identification was confirmed by sequence analysis of the internal transcribed spacer (ITS-S2) region. The results of the susceptibility testing showed voriconazole as the most active drug. Despite adaptation of the antifungal therapy the clinical condition worsened, and the patient died. In addition, we evaluated the fungicidal activity of antiseptics towards E. dermatitidis and aimed to provide a brief literature review of previously reported infections caused by this rare fungus. To the best of our knowledge, this is the first report of a rapidly progressing invasive fungal infection with E. dermatitidis originating from a colonized wound after lung transplantation.(VLID)365876

Microsaccades during high speed continuous visual search

Here, we provide an analysis of the microsaccades that occurred during continuous visual search and targeting of small faces that we pasted either into cluttered background photos or into a simple gray background. Subjects continuously used their eyes to target singular 3-degree upright or inverted faces in changing scenes. As soon as the participant’s gaze reached the target face, a new face was displayed in a different and random location. Regardless of the experimental context (e.g. background scene, no background scene), or target eccentricity (from 4 to 20 degrees of visual angle), we found that the microsaccade rate dropped to near zero levels within only 12 milliseconds after trial onset. There were almost never any microsaccades before the saccade to the face. One subject completed 118 consecutive trials without a single microsaccade. However, in about 20% of the trials, there was a single corrective microsaccade that occurred almost immediately after the preceding saccade’s offset. These corrective microsaccades were task oriented because their facial landmark targeting distributions matched those of saccades within both the upright and inverted face conditions. Our findings show that a single feedforward pass through the visual hierarchy for each stimulus is likely all that is needed to effectuate prolonged continuous visual search. In addition, we provide evidence that microsaccades can serve perceptual functions like correcting saccades or effectuating task-oriented goals during continuous visual search

The role of community pharmacists in immunisation: a national cross-sectional study.

Background Austrian pharmacists are not authorised to administer immunisations, and evidence about their willingness to immunise is lacking. Aim The aim of this study is to investigate Austrian community pharmacists’ willingness to administer immunisations in the future. Method This study is designed as a cross-sectional online survey based on the theoretical domains framework (TDF). The validated and piloted questionnaire obtained ethical approval by Robert Gordon University. Outcome measures included pharmacists’ willingness to immunise, service requirements, barriers and education needs. Results The questionnaire was sent out to 3086 community pharmacists of which 380 responses were included in the final analysis (12.3%). Willingness to administer immunisations after appropriate training and legislative regulation was stated by 82.6% (n = 314) of participants. It was demonstrated that pharmacists willing to immunise were significantly younger than their counterpart (38 [IQR 31–49] years vs. 45 [IQR 37.5–54] years; OR 1.06; 1.03–1.09, 95% CI; p < 0.001). ‘Legal liability’ was considered the most critical barrier to service implementation, ‘seeing blood’ and ‘close patient contact’ as least critical. Pharmacists not willing to immunise showed a higher probability to evaluate personnel resources (OR 2.98; 1.35–6.58, 95% CI; p = 0.007), close patient contact (OR 2.79; 1.46–5.34, 95% CI; p = 0.002) and management of side effects (OR 2.62; 1.21–5.67, 95% CI; p = 0.015) as (highly) critical. The majority assessed the ‘right timing for training’ to be after the foundation training with a 2-yearly renewal. Conclusion Austrian community pharmacists show a strong willingness to administer immunisations while highlighting important requirements and barriers towards service implementation