Stochastic modelling of transition dynamic of mixed mood episodes in bipolar disorder

In the present state of health and wellness, mental illness is always deemed less importance compared to other forms of physical illness. In reality, mental illness causes serious multi-dimensional adverse effect to the subject with respect to personal life, social life, as well as financial stability. In the area of mental illness, bipolar disorder is one of the most prominent type which can be triggered by any external stimulation to the subject suffering from this illness. There diagnosis as well as treatment process of bipolar disorder is very much different from other form of illness where the first step of impediment is the correct diagnosis itself. According to the standard body, there are classification of discrete forms of bipolar disorder viz. type-I, type-II, and cyclothymic. Which is characterized by specific mood associated with depression and mania. However, there is no study associated with mixed-mood episode detection which is characterized by combination of various symptoms of bipolar disorder in random, unpredictable, and uncertain manner. Hence, the model contributes to obtain granular information with dynamics of mood transition. The simulated outcome of the proposed system in MATLAB shows that resulting model is capable enough for detection of mixed mood episode precisely

Capillary-Like Formations of Endothelial Cells in Defined Patterns Generated by Laser Bioprinting

Bioprinting is seen as a promising technique for tissue engineering, with hopes of one day being able to produce whole organs. However, thick tissue requires a functional vascular network, which naturally contains vessels of various sizes, down to capillaries of ~10 µm in diameter, often spaced less than 200 µm apart. If such thick tissues are to be printed, the vasculature would likely need to be printed at the same time, including the capillaries. While there are many approaches in tissue engineering to produce larger vessels in a defined manner, the small capillaries usually arise only in random patterns by sprouting from the larger vessels or from randomly distributed endothelial cells. Here, we investigated whether the small capillaries could also be printed in predefined patterns. For this purpose, we used a laser-based bioprinting technique that allows for the combination of high resolution and high cell density. Our aim was to achieve the formation of closed tubular structures with lumina by laser-printed endothelial cells along the printed patterns on a surface and in bioprinted tissue. This study shows that such capillaries are directly printable; however, persistence of the printed tubular structures was achieved only in tissue with external stimulation by other cell types.

Rhythmic tapping difficulties in adults who stutter: a deficit in Central Clock and/or Motor Implementation?

The study aims to better understand the origin of increased tapping variability and inaccuracy in people who stutter during paced and un-paced tapping. The overall question is to what extent these timing difficulties are related to a central clock deficit, a deficit in motor execution, or both.Finger tapping behavior of 16 adults who stutter (PWS) with different levels of musical training was compared with performance of 16 matching controls (PNS) in three finger tapping synchronization tasks ― a simple 1:1 isochronous pattern, a complex non-isochronous pattern, and a 4 tap:1 beat isochronous pattern ―, a continuation task (without external stimulation), and a reaction task involving aperiodic and unpredictable patterns. The results show that PWS exhibited larger negative asynchrony (expressed as phase angles), and increased synchronization variability (expressed as phase locking values) in paced tapping tasks, and that these differences from the PNS group were modulated by rhythmic complexity and musical training. The tapping asynchrony with a simple isochronous pattern correlated significantly with the average inter-tap duration, and with tap reaction times during the reaction task. The synchronization variability with a simple isochronous pattern correlated significantly with both the central clock and motor implementation variances as extracted during un-paced tapping, according to the Wing and Kristofferson’s model of timing.The results support the idea that increased tapping variability of PWS is associated with both a central clock and a motor execution deficit. The greater Negative Mean Asynchrony of PWS does not appear to be attributable to a deficit in time estimation but rather to a motor deficit. Several models and theories related to deficits in sensorimotor integration were considered to explain the interactions with beat strength, pattern complexity, and musical training.

Tinnitus-like “hallucinations” elicited by sensory deprivation in an entropy maximization recurrent neural network

Sensory deprivation has long been known to cause hallucinations or “phantom” sensations, the most common of which is tinnitus induced by hearing loss, affecting 10–20% of the population. An observable hearing loss, causing auditory sensory deprivation over a band of frequencies, is present in over 90% of people with tinnitus. Existing plasticity-based computational models for tinnitus are usually driven by homeostatic mechanisms, modeled to fit phenomenological findings. Here, we use an objective-driven learning algorithm to model an early auditory processing neuronal network, e.g., in the dorsal cochlear nucleus. The learning algorithm maximizes the network’s output entropy by learning the feed-forward and recurrent interactions in the model. We show that the connectivity patterns and responses learned by the model display several hallmarks of early auditory neuronal networks. We further demonstrate that attenuation of peripheral inputs drives the recurrent network towards its critical point and transition into a tinnitus-like state. In this state, the network activity resembles responses to genuine inputs even in the absence of external stimulation, namely, it “hallucinates” auditory responses. These findings demonstrate how objective-driven plasticity mechanisms that normally act to optimize the network’s input representation can also elicit pathologies such as tinnitus as a result of sensory deprivation.

Intranasal Administration as a Route to Deliver Drugs to the Brain (Review)

Introduction. Intranasal drug delivery from nose-to-brain is one of the promising approaches for the treatment of brain diseases including neurodegenerative diseases, stroke, brain tumors, etc.Text. Delivery of drugs through the nose has a number of advantages, including the rapid onset of a pharmacological effect, the ability to bypass the blood-brain barrier, avoidance of some side effects and fast and non-invasive route of administration. However, the significant disadvantages of this route are rapid elimination of the drug from the surface of the mucosal membrane, poor penetration of the drug through the nasal mucosa, mucociliary clearance and effects of proteolytic enzymes. Currently, to overcome the above limitations, various approaches are used, including the development of delivery systems from nose-to-brain, which are mucoadhesive, mucus-penetrating and gel-forming systems that facilitate the retention or penetration of drugs through the mucosal membranes. At the same time, high-molecular weight compounds play a significant role in the design of these systems. In particular, mucoadhesive systems can be prepared from cationic and anionic polymers. Recent studies have also shown that interpolyelectrolyte complexes also exhibit mucoadhesive properties. An improvement in mucoadhesive properties of polymers can also be achieved by conjugating various functional groups such as thiols, maleimides, acrylates, methacrylates, catechols, etc. Mucus-penetrating systems can be prepared by PEGylation of nanoparticles, as well as functionalization with some poly(2-oxazolines), polyvinyl alcohol, etc. The mucus-penetrating ability of these polymers has been shown in other mucosal membranes in the body. Finally, increased penetration can be achieved by using mucolytic agents in combination with non-ionic surfactants. Another approach to increase the efficiency of drug delivery from nose-to-brain is the use of in situ gelling systems. Initially, this type of formulation exists as a solution; then a phase transition to gel is observed in response to chemical and physical effects. Depending on the external stimulation of the phase transition, thermo-, pH-, ion-reversible and other systems are known. These systems have shown effectiveness for delivery to the brain by intranasal administration.Conclusion. Effective intranasal delivery of drugs and therapeutic agents to the brain can be achieved by using mucoadhesive, mucus-penetrating, gelling systems and/or their combinations.

The effect of external stimulation on functional networks in the aging healthy human brain

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve as a more specific biomarker relating local activity with global brain dynamics. Here, we used a large resting-state fMRI dataset divided into middle-aged (N=310, aged < 65 years) and older adults (N=310, aged >= 65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space, each with a probabilistic occurrence and frequency. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations with different intensities in each node to force transitions from the brain states of the older group to the middle-age group. We found that the precuneus, a brain area belonging to the default mode network and the rich club, was the best stimulation target. These findings might have important implications for designing neurostimulation interventions to revert the effects of aging on whole-brain dynamics.

The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes

Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.

Mathematical modeling of a new way of renal artery denervation

The aim of the work is to create a new design of electrodes for renal denervation. In standard RFA systems, monopolar heating is most often used, by introducing an RF electrode inside the vessel. This approach leads to the need to interrupt blood flow during the procedure. In addition, the monopolar mode of operation requires the contact of the inserted electrode with the vessel walls, which greatly complicates the design of the electrode system. Point contact of the electrode system with the vessel can damage the inner walls of the artery. It is proposed to use a multi-electrode structure for external stimulation by creating a hollow cylindrical thermal field for effective treatment. It has been established that external heating will create the required thermal field without direct contact with the walls of the artery. The external arrangement of the electrodes makes it possible to regulate the temperature on the external surface of the vessel. With such heating, it is not necessary to block the blood flow, and due to the symmetry of the arrangement, continuous heating can be obtained without moving the electrodes during the procedure. Mathematical modeling confirms the possibility of vascular denervation during external heating.