Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR−/−; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways. Hallmarks of metabolic cardiomyopathy were increased activity in integrin-linked kinase signalling, Rho signalling, dendritic cell maturation, production of nitric oxide and reactive oxygen species in macrophages, atherosclerosis, LXR-RXR signalling, cardiac hypertrophy, and acute phase response pathways. ACE-inhibition had a limited effect on gene expression in WT (55 genes, 23 pathways), and a prominent effect in DKO hearts (1143 genes, 104 pathways). In DKO hearts, ACE-I appears to counteract some of the MetS-specific pathways, while also activating cardioprotective mechanisms. We conclude that MetS and control murine hearts have unique transcriptional profiles and exhibit a partially specific transcriptional response to ACE-inhibition.
The article includes the observation of the cloud services and technologies usage. The article contains a review of mathematical analysis of cardiac information using cloud technology, which produces storage, analysis and forecasting on the basis of owned data. In addition, the authors consider the possibility of integrating cloud technologies with external systems. The massive use of mobile devices for the removal of the electrocardiogram (ECG) leads to a quantitative increase of the patients number available for ECG investigation. Thus, there are new opportunities to research the oscillatory processes of long-term dynamics of the individual state of the cardiovascular system (CVS) of any patient. The article demonstrates new opportunities the long-term continuous monitoring of the patients CVS, which allows identifying regularities of the dynamics of the CVS. Also this article comprises the observation of the existence of an adequate model of CVS as a distributed nonlinear self-oscillating system of the class model returns the Fermi-Pasta-Ulam (FPU).
After a protracted history, neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream (Kamiya, 2011; Linden, 2014; Sitaram et al., 2017). A debate now centres on the extent to which neurofeedback alters brain function and behaviour, and the mechanisms through which neurofeedback operates (e.g., neurofeedback-specific versus nonspecific). A series of correspondences in Lancet Psychiatry (Micoulaud-Franchi & Fovet, 2016; Pigott et al., 2017; Schönenberg et al., 2017b, 2017a; Thibault & Raz, 2016a, 2016b) and Brain (Fovet et al., 2017; Schabus, 2017, 2018; Schabus et al., 2017; Thibault, Lifshitz, & Raz, 2017, 2018; Witte, Kober, & Wood, 2018) discusses the theoretical arguments and empirical data backing the involvement of these two mechanisms.
Intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1) can produce percepts that mimic somatic sensation and, thus, has potential as an approach to sensorize prosthetic limbs. However, it is not known whether ICMS could recreate active texture exploration-the ability to infer information about object texture by using one's fingertips to scan a surface. Here, we show that ICMS of S1 can convey information about the spatial frequencies of invisible virtual gratings through a process of active tactile exploration. Two rhesus monkeys scanned pairs of visually identical screen objects with the fingertip of a hand avatar-controlled first via a joystick and later via a brain-machine interface-to find the object with denser virtual gratings. The gratings consisted of evenly spaced ridges that were signaled through individual ICMS pulses generated whenever the avatar's fingertip crossed a ridge. The monkeys learned to interpret these ICMS patterns, evoked by the interplay of their voluntary movements and the virtual textures of each object, to perform a sensory discrimination task. Discrimination accuracy followed Weber's law of just-noticeable differences (JND) across a range of grating densities; a finding that matches normal cutaneous sensation. Moreover, 1 monkey developed an active scanning strategy where avatar velocity was integrated with the ICMS pulses to interpret the texture information. We propose that this approach could equip upper-limb neuroprostheses with direct access to texture features acquired during active exploration of natural objects.
The paper presents a possibility of estimating a human cardiac pacemaker using combined application of nonlinear integral transformation and fuzzy logic, which allows carrying out the analysis in the real-time mode. The system of fuzzy logical conclusion is proposed, membership functions and rules of fuzzy products are defined. It was shown that the ratio of the value of a truth degree of the winning rule condition to the value of a truth degree of any other rule condition is at least 3.
The idea of forced external synchronization of the heart dynamics by the canonical FPU spectrum with a purpose to lower the rate of its desynchronization in some pathological cases has been hypothesized by the authors. It was concluded that a heart being a multi resonant distributed dynamic ion containing system may be resonantly influenced by applying to it the canonical FPU electromagnetic spectrum, which can supposedly decrease the rate of desynchronization in the ECG Fourier spectrum for example in case of arrhythmia. The complex FPU recurrences found in the deep-water dynamics studies were compared with real ECG Fourier images in a sequence of time periods. For choosing the appropriate form of the external FPU canonical spectrum, the two different forms of the ECG Fourier spectra were studied: a rectangular pulse spectrum and exponential pulse spectrum. The two functions were taken to form the external synchronizing canonical FPU recurrence spectrum and were put into the right part of the equations of the previously developed mathematical model as perturbing functions. The computer study of the model simulating arrhythmia with a synchronizing perturbing part in a form of the canonical FPU recurrence spectrum changed the solutions of the model to the forms characteristic for normally functioning heart. Thus, the hypothesis has been confirmed,
The Internet comprises a decentralized global system that serves humanity's collective effort to generate, process, and store data, most of which is handled by the rapidly expanding cloud. A stable, secure, real-time system may allow for interfacing the cloud with the human brain. One promising strategy for enabling such a system, denoted here as a "human brain/cloud interface" ("B/CI"), would be based on technologies referred to here as "neuralnanorobotics." Future neuralnanorobotics technologies are anticipated to facilitate accurate diagnoses and eventual cures for the ∼400 conditions that affect the human brain. Neuralnanorobotics may also enable a B/CI with controlled connectivity between neural activity and external data storage and processing, via the direct monitoring of the brain's ∼86 × 109 neurons and ∼2 × 1014 synapses. Subsequent to navigating the human vasculature, three species of neuralnanorobots (endoneurobots, gliabots, and synaptobots) could traverse the blood-brain barrier (BBB), enter the brain parenchyma, ingress into individual human brain cells, and autoposition themselves at the axon initial segments of neurons (endoneurobots), within glial cells (gliabots), and in intimate proximity to synapses (synaptobots). They would then wirelessly transmit up to ∼6 × 1016 bits per second of synaptically processed and encoded human-brain electrical information via auxiliary nanorobotic fiber optics (30 cm3) with the capacity to handle up to 1018 bits/sec and provide rapid data transfer to a cloud based supercomputer for real-time brain-state monitoring and data extraction. A neuralnanorobotically enabled human B/CI might serve as a personalized conduit, allowing persons to obtain direct, instantaneous access to virtually any facet of cumulative human knowledge. Other anticipated applications include myriad opportunities to improve education, intelligence, entertainment, traveling, and other interactive experiences. A specialized application might be the capacity to engage in fully immersive experiential/sensory experiences, including what is referred to here as "transparent shadowing" (TS). Through TS, individuals might experience episodic segments of the lives of other willing participants (locally or remote) to, hopefully, encourage and inspire improved understanding and tolerance among all members of the human family.
Nucleic acids labeled with a fluorophore/quencher pair are widely used as probes in biomedical research and molecular diagnostics. Here we synthesized novel DNA molecular beacons double labeled with the identical dyes (R6G, ROX and Cy5) at 5′- and 3′-end and studied their photo physical properties. We demonstrated that fluorescence quenching by formation of the homo dimer exciton in such molecular beacons allows using them in homogeneous assays. Further, we developed and evaluated homo Yin-Yang DNA probes labeled with identical dyes and used them for detection of low copy HIV RNA by RT-qPCR. They demonstrated improved sensitivity (LLQ: 10 vs 30 copies mL-1) in comparison to commercially available Abbott RealTime HIV-1 kit based on VICBHQ dyes both for model mixtures (naive human plasma with added deactivated HIV-1 virus) and for preliminarily confirmed 36 clinical samples (4 vs 1 positive ones for low-copy samples).
Paired-pulse transcranial magnetic stimulation (TMS) allows investigating inhibitory and excitatory interactions in the human motor cortex noninvasively. Short-interval intracortical inhibition (SICI) and facilitation (SICF) are used to measure cortico–cortical excitability in patients with, e.g., stroke, dystonia, and Parkinson’s disease. However, the role of the induced electric field (E-field) orientation remains partly unclear. Posterior–anterior (PA)-oriented E-field elicits motor evoked potentials (MEPs) with the lowest stimulus intensities due to the recruitment of corticospinal neurons, indirectly via excitatory synaptic inputs to corticospinal axons (indirect (I-) waves). Stimulation in the lateral–medial (LM) orientation directly activates corticospinal axons, which leads to the generation of both direct (D-) and I-waves. Conditioning stimulus (CS) with an intensity between 50% and 90% of resting motor threshold (RMT) induces activation of GABAA inhibitory mechanisms observed as the SICI (inhibitory) effect on MEP amplitude. In contrast, if the CS intensity is above RMT, the SICF (excitatory) phenomenon can be present due to the superposition of D- and I-waves. Our aim was to investigate the dependence of inhibitory and facilitatory mechanisms on the orientation of the induced E-field of CS and TS. We developed a multi-locus TMS (mTMS) transducer, which allowed us to control the E-field orientation independently for CS and TS at a millisecond inter-pair interval (IPI). Eight healthy subjects (five males; mean age 29, range 21–35 years) participated in the study. mTMS was applied to the hotspot of the abductor pollicis brevis (APB) muscle in the left primary motor cortex. The stimulus intensities were based on the individual RMT of APB for PA and LM orientations. TS and single pulses were administered at 110% RMT. Twenty single pulses were applied for each TS orientation and for each of the 32 paired-pulse conditions. CS and TS stimuli were applied in every combination of the PA and LM orientations with four CS intensities (50, 70, 90, and 110% RMT) and two IPIs (1.5 and 2.7 ms) in a random order. Interaction between CS orientation, IPI, and CS intensity significantly affected TS MEP amplitudes. We observed no statistically significant difference between the responses induced by PA- and LM-oriented TS. CS at 70% RMT for SICI and at 110% RMT for SICF induced similar effects regardless of the TS orientation. We established that LM-oriented CS at 90% RMT produced a greater inhibition than stimuli at the same intensity in the PA orientation. Our results emphasize the minimal influence of the CS E-field dorientation on the test pulse. Additionally, we demonstrate the pivotal role of the stimulus intensity for any CS orientation. SICI and SICF evoked using perpendicular CS and TS directions indicate that we stimulated overlapping neuronal populations with both pulses.
Increasing evidence suggests that neuronal communication is a defining property of functionally specialized brain networks and that it is implemented through synchronization between population activities of distinct brain areas. The detection of long-range coupling in electroencephalography (EEG) and magnetoencephalography (MEG) data using conventional metrics (such as coherence or phase-locking value) is by definition contaminated by spatial leakage. Methods such as imaginary coherence, phase-lag index or orthogonalized amplitude correlations tackle spatial leakage by ignoring zero-phase interactions. Although useful, these metrics will by construction lead to false negatives in cases where true zero-phase coupling exists in the data and will underestimate interactions with phase lags in the vicinity of zero. Yet, empirically observed neuronal synchrony in invasive recordings indicates that it is not uncommon to find zero or close-to-zero phase lag between the activity profiles of coupled neuronal assemblies. Here, we introduce a novel method that allows us to mitigate the undesired spatial leakage effects and detect zero and near zero phase interactions. To this end, we propose a projection operation that operates on sensor-space cross-spectrum and suppresses the spatial leakage contribution but retains the true zero-phase interaction component. We then solve the network estimation task as a source estimation problem defined in the product space of interacting source topographies. We show how this framework provides reliable interaction detection for all phase-lag values and we thus refer to the method as Phase Shift Invariant Imaging of Coherent Sources (PSIICOS). Realistic simulations demonstrate that PSIICOS has better detector characteristics than existing interaction metrics. Finally, we illustrate the performance of PSIICOS by applying it to real MEG dataset recorded during a standard mental rotation task. Taken together, using analytical derivations, data simulations and real brain data, this study presents a novel source-space MEG/EEG connectivity method that overcomes previous limitations and for the first time allows for the estimation of true zero-phase coupling via non-invasive electrophysiological recordings.
The ECG features analysis in a patient born in 1946 led to repeated statement of misdiagnosis, particularly of myocardial infarction. About 2,500 patients’s ECGshave been analyzed for the three-year period of the patient’s observation. A Fourier analysis of the spectra of the ECGs of the patient 2506 allowed to assume that there exists an additional leading center in his myocardium, with a variable start phase of the myocardium relative to the phase of the fundamental frequency of contractions of the myocardium. Experimental confirmation of this hypothesis is in particular; found in the patient jump-like transition from synchronous phase daily changes in the function dynamics of the P wave width and the PQ segment to the antiphase ones, which reflects the change in the conditions for triggering the process of myocardial contraction. As a result, the coupling of the two leading frequencies of the myocardium, with a variable phase shift of the triggering, can be expressed both in the extra systoles appearance as well as in unusual cardio cycles not coinciding in the form and phase of cardio cycles of a single ECG. Cluster analysis of the entire set of collected patient’s ECGs in the similarity of their forms revealed 18 separate clusters of similarity. While cluster analysis of the ECG samples in other 4857 patients in most cases led to the identification of only one cluster characteristic for a certain patient’s ECG form. Mathematical modeling of the proposed hypothesis about the presence of more than one leading center of myocardial triggering which resulted in getting model patterns of split ECGs, qualitatively corresponding to the split forms of ECGs observed in the studied patient, confirmed its validity.
The paper presents the automated system intended to prevent industrial-caused diseases of workers, the basis of which is represented by algorithms of preventing several negative functional conditions (stress, monotony). The emergence of such state shall be determined based on an analysis of bioelectric signals, in particular, skin-galvanic reactions. Proceeding from the dynamics of the functional state, the automated system offers to perform an optimized set of measures to restore the health of the worker. Implementation of an automated system is presented in Visual Programming system LabVIEW.
Previously, the mathematical models (CoMPaS and CoM-III) of primary tumor (PT) growth and secondary distant metastases (sdMTS) growth of breast cancer (BC) considering TNM classification have been presented (Tyuryumina E., Neznanov A.; 2017, 2018). Goal: To detect the earliest diagnostics period of visible sdMTS via CoMPaS and CoM-III.
Transcranial magnetic stimulation (TMS) is a powerful tool for non-invasive brain modulation and investigation in normal and pathological conditions. One of the most serious problems limiting the TMS use is the high variability of its effects. In recent years, it became widely accepted that the effect of the TMS protocol is not a property of the protocol itself, but a consequence of the interactions of TMS with the neuronal system trait and state. Thus, it is necessary to develop TMS approaches that take into account the ongoing neuronal activity, the so-called state/activity-dependent TMS. This paper presents software that allows considering both the position of the stimulator and the ongoing neuronal activity for TMS triggering. Automatic TMS initiation was demonstrated when all the conditions were met (the beginning of the movement execution, lack of the unnecessary preactivation, the proper coil position). The delay for TMS triggering was tested in an experiment with stimulation triggered by the onset of the desired movement. The development of such technical solution for neuronavigated activity-dependent TMS is important to bring TMS methodology to a new level of its individualized application.
Purpose: Determination of transluminal attenuation gradient (TAG) in intact cor onary arteries
Material and methods. 122 patients had been scheduled for elective lumbar fusion in 2010-2016 was enrolled in a prospective study. Group K (n=19) underwent postoperative analgesia on-demand. Group PMA (n=21) was given preventive multimodal analgesia (PMA) including ketoprofen, paracetamol and morphine. At PMA+PG (n=20) and PMA+N (n=20) groups pregabalin and nefopam were used respectively; at PMA+E (n=22) epidural ropivacaine with morphine was combined; at PMA+I (n=20) continuous wound infiltration by ropivacaine with ketorolac was administered. Results and conclusions. Postoperative analgesia on-demand is not adequate during 5 postoperative days. PMA results in significant pain reduction during 3 postoperative days, enhancement of patient satisfaction, quicker recovery after surgery and fewer days of hospital stay. Patients receiving pregabalin or nefopam as well as epidural analgesia does not lead to better postoperative pain relief than at PMA, but shows a trend to increase the rate of adverse reactions. Wound infiltration with PMA is followed by significant pain relief during 6 postoperative hours, decrease in opioids consumption, rate of adverse reactions and duration of hospital stay (compared to PMA group).
Transcranial magnetic stimulation is a method of focal non-invasive brain stimulation, characterized by high spatial and temporal resolution. To date, diagnostic transcranial magnetic stimulation has been used in clinical practice primarily to assess an involvement of the upper motor neurons and to measure the velocity of the neuronal impulse propagation. However, in the last 10 years, a possible range of transcranial magnetic stimulation diagnostic applications has significantly expanded. Many transcranial magnetic stimulation approaches are coming from scientific laboratories to clinical practice due to an increased availability of transcranial magnetic stimulation equipment, in particular, magnetic resonance imaging navigation for transcranial magnetic stimulation and a combination of the transcranial magnetic stimulation with electroencephalography and also due to an increased awareness of the clinicians. The diagnostic potential of transcranial magnetic stimulation in relation to motor recovery after a stroke can be classified into 4 directions:
1) assessment of the vertical tracts integrity (primarily, the cortico-spinal tract); 2) an assessment of the cortical excitation-inhibition balance;
3) probing of the functional and effective connectivity among brain regions (primarily, cortical convexity and cerebellum);
4) motor mapping to evaluate cortical reorganization.
In this article we will present these 4 directions of the transcranial magnetic stimulation application to study motor system pathophysiology and to predict motor outcome in stroke, including both existing and developing approaches.
The paper analyses regulatory frameworks for telemedicine in employment relations in Russia and abroad in a comparative context. The author considers the topic from two viewpoints: firstly, as a service employer and employee use to simplify statutory procedures that relate to employee health, and secondly, as work duties healthcare professionals perform in the course of their employment relations bearing specific liabilities and sustaining specific consequences. In conclusion, the author formulates recommendations for amendments to national legislation.
The article includes the observation of the cluster analysis of medical data on the example of the cardiac data. One of the main effective and commonly used Data Mining methods that applied to the large amounts of information (for example, mathematical economics) are clustering methods: the search for signs of similarity between objects in the study of the subject area and the subsequent merger of objects into subsets (clusters) according to the established affinity. The main purpose of the investigation is to examine the hypothesis of the possibility of diagnosing the patient health status, as well as identifying his pathologies, using the analysis of electrocardiogram (ECG) series and the allocation of similar clusters based on the results of this analysis. However, the subject of clustering techniques implementation to the ECG on the grounds of similarity of forms have not previously been extensively investigated. In the model of the heart, which is used in this study, the state of the heart is taken as a fixed oscillatory process of the phenomenon of the FPU auto-return. But, on the other hand, since the heart is an self-oscillating system and it has no need to start the oscillations by obtaining the energy of “perturbation”, the concept of FPU autoreturn is introduced in the study of the heart. The mathematical modeling of the heart work by using a decomposition of the Fermi-Pasta-Ulam (FPU) was investigated. The formal description of the mathematical model of the heart as a system of connected cells myocytes is presented. This represents a single oscillatory degree of freedom described by a system of coupled nonlinear differential equations of the second order equation of Van der Pol. Cluster analysis bases on the search of similar clusters of Fourier spectrum which are received by FPU recurrence. The current results that are obtained show that the hypothesis is confirmed. In mathematical modeling of the FPU heart modeling, which is based on the forms of Fourier spectra, were identified. Subsets were identified, among which various subsets of both forms of Fourier spectra with pathologies and forms of the Fourier spectrum of healthy people were formed. From this study it follows that the cluster analysis of the electrocardiogram may refer this ECG to any cluster and thereby diagnose the state of cardiac health of the patient.
It is necessary not only to develop information and communication infrastructures and algorithms for distributed and cloud processing of data coming from all kinds of sensors and sensors, but also to design new materials that enable the production of safe, effective and accessible to the general public test systems when creating digital health saving systems as part of the development of modern electronic medical monitoring technologies. An analysis of the market for consumables intended for use in rapid diagnostic devices shows that disposable test strips on a flexible polymer base with high biological resistance to the effects of blood components are most in demand. It has been shown that surface modification of polyethylene by fluorination, sulfonation and plasmification methods provides a significant reduction in platelet adhesion to processed polymer films. It was also suggested that the surface energy of the modified material has a determining effect on its hemocompatibility.This work is devoted to the formation of an analytical model of the surface morphology of fluorinated polyethylene, as well as a quantitative analysis of the structural and functional relationships between the parameters of the morphological model and the resistance of the material to platelet adhesion. The widespread use of the discussed approach to increasing the thromboresistance of polymeric materials will increase the reliability of glycemic analyzes performed by patients on their own using portable express diagnostic systems (glucometers).