Development of a neurointerface glove with tactile feedback
Research Question or Engineering Problem A stroke continues to be the most important medical and social problem of the modern world. Stroke is a type of acute cerebrovascular accident (ACVA) and is characterised by a sudden (within minutes, less often - hours) appearance of focal neurological symptoms (motor, speech, sensory, coordinating, visual and other disorders) and / or general brain disorders (depression of consciousness, headache, vomiting, etc.) that persist for more than 24 hours or lead to death of the patient in a short period of time due to a cause of cerebrovascular origin. There are two clinical and pathogenetic forms of stroke: ishemic stroke (cerebral infarction) is caused by acute focal cerebral ischemia, leading to infarction (zone of ischemic necrosis) of the brain; hemorrhagic stroke (non-traumatic intracerebral hemorrhage) is caused by rupture of an intracerebral vessel and blood penetration into the brain parenchyma or rupture of an arterial aneurysm with subarachnoid hemorrhage (SAH). ACVA also includes transient disorders of cerebral circulation, characterised by the sudden occurrence of focal neurological symptoms that develop in a patient with cardiovascular disease (arterial hypertension, atherosclerosis, atrial fibrillation, vasculitis, etc.), last for several minutes, less often hours, but no more than 24 hours, and ends with a full restoration of the impaired brain functions. Transient disorders of cerebral circulation include: transient ischemic attack (TIA), which develops as a result of short-term local cerebral ischemia and is characterised by sudden transient neurological disorders with focal symptoms; hypertensive cerebral emergency, which is a condition associated with an acute (usually significant) rise in blood pressure (BP) and accompanied by the appearance of general cerebral (less often focal) neurological symptoms secondary to hypertension. The most severe form of hypertensive crisis is acute hypertensive encephalopathy, the basis of pathogenesis of which is cerebral edema. Cerebral infarction generally is the result of the interaction of many etiopathogenetic factors, which can be subdivided into local and systemic ones. Local factors include: morphological changes in the brachiocephalic or intracerebral arteries (pathological tortuosity, etc.), atherosclerotic lesions of the vessels of the aortic arch and cerebral arteries, cardiac lesions as a source of thromboembolic cerebral infarctions, fibromuscular dysplasias of the walls of the brachiocephalic and cerebral arteries, brachiocephalic artery dissection, vasculitis (arteritis), changes in the cervical spine with the formation of extravasal compression of the vertebral arteries, anomalies in the structure of the vessels of the neck and brain (hypoplasia of the vertebral artery, trifurcation of the internal carotid artery), etc. Systemic factors include: disorders of central and cerebral hemodynamics (a sharp change in BP or a decrease in cardiac output, etc.), hereditary and acquired coagulopathies, polycythemia, certain forms of leukemia, hypovolemia, psychoemotional stress / distress, etc., hypercoagulative / hyperaggregatory side effects of a number of medications (oral contraceptives, etc.). In the 俄羅斯n Federation, more than 500 thousand people have a stroke every year. About 25,000 new cases of stroke occur in St. Petersburg every year. The incidence of stroke in the 俄羅斯n Federation is 3.48 ± 0.21 cases per 1000 people. The incidence of various types of ACVA varies widely, in particular, cerebral infarctions account for 65–75%, hemorrhages (including subarachnoid hemorrhages) – 15–20%, transient cerebral circulation disorders account for 10–15%. The frequency of cerebral strokes in the population over 50–55 years old increases by 1.8–2 times in each subsequent decade of life. Medical and socio-economic consequences of ACVA are very significant, in particular, death in the acute period of stroke occurs in 34.6% cases, during the first year after the end of the acute period in 13.4% cases; severe disability with the need for constant care is present in 20.0% of stroke patients; 56.0% have limited working capacity and only 8.0% return to their previous work activity. Disability due to stroke (the national average is 56–81%) in our country ranks first among all causes of primary disability, amounting to 3.2 per 10 thousand people. Stroke mortality among working-age population has increased in the 俄羅斯n Federation by more than 30% over the past 10 years. The annual death rate from stroke in our country is 175 per 100 thousand people. Stroke annually becomes the main cause of disability: 85% of victims experience a decrease in strength or a complete lack of ability to control the muscles of half of the body and only half of them recover limb functions partially or completely; the rest of those who have suffered a stroke remain paralysed and require care, since they are not able to completely independent existence. In this regard, recently, in the process of rehabilitation, the technology of brain-computer interfaces (BCI) has begun to be actively used. on the basis of this technology exercise machines are created. These exercise machines are controlled directly by the patient himself. This feature of the technology increases the effect of the procedure by providing a direct connection between the patient's desire and effort with the work of the simulator. The greatest development of this technology is observed in the field of medicine, where BCIs are used as a means of communication or as one of the tools of neurorehabilitation. In this regard, it seems very promising to develop the most optimal brain-computer interfaces. The goal of our project was to create an automated training complex in the form of a neuro-controlled glove with tactile feedback, designed to simplify access to rehabilitation means.
THE DESIGN OF MICROFLUIDIC PUMP (MFP) FOR MEDICAL FIELD
The ability of microfluidic (MF) device technologies to provide a lot of information with a small amount of sample, the opportunities it offers increases their use in the medical field in the bedside monitoring in drug delivery systems. Three-dimensional (3D) printer technologies provide advantages such as cost-effectiveness in the production of MF devices and quick and easy production in intricate designs. In our project, it is aimed to design microfluidic pumps (MFP) to be used in the medical field and conduct its production with 3D printer technologies. The developed MFP is intended to be at low cost, bio-compatible, adaptable, and portable to the drug, suitable flow properties as a pharmaceutical pump. First of all, MFP air channel, flow channel, etc. parts were designed and printed with the help of a 3D printer and on AutoCAD, one of the professional drawing programs. The poly(dimethylsiloxane) (PDMS) membrane that will enable MFP activation is produced in different thicknesses and glued to the air channel of MFP. The resistance to the applied pressure is observed, and the appropriate membrane thickness is determined as ~ 235µm. Liquid PDMS was applied to the inner surfaces of MFP's air and flow channel, PDMS membrane was placed between them, and the parts were assembled in the oven at 60ºC. MFP has been connected to the pneumatic valve system, where operation codes have been prepared with Arduino Uno, and flow properties have been examined. The flow rate of MFP is ~ 50 µL/min at a maximum of 15 Hz, and the backpressure is ~ 0.085 Pa under a maximum pressure of 3 bar. Also, values such as size, membrane thickness, and applied pressure for the possible models of MFP were supported by theoretical calculations. As a result, MFP, which is biocompatible, drug adaptable, portable, wearable technology application potential, and has suitable flow characteristics as a pharmaceutical pump, has been developed. MFP introduced a microfluidic pump system that can make life easier for the patient and contribute to the national economy through domestic production and can be used as a drug pump in the treatment of diseases such as diabetes and cancer.
Anti-bacterial Crab bio-bandages with Bio-dressings 2.0
Commercially available bandages such as hydrocolloid are neither biodegradable nor anti-bacterial. Chitin is known to be the second most naturally available polysaccharide which could be transformed to chitosan which is known to be anti-bacterial (Hasan, 2018) (Chao, 2019) and haemostatic (Okamoto, 2003) (Hu, 2018). Chitosan can be further converted to hydrogel which is bio-degradable and has good water absorbance. Anti-bacterial crab bio-bandages and crab bio-dressings should be bio-degradable as it took 42 days and a month for complete bio-degradation respectively, so they should be better than commercial bandages such as Nexcare Hydrocolloid as the disposal of anti-bacterial crab bio-bandages with bio-dressings would no longer pose burden to landfilling or threat to our environment. Anti-bacterial crab bio-bandages with bio-dressings are anti-bacterial with degree of deacetylation of DD% (measured using FTIR Spectrum II) 82.6% (due to the presence of chitosan) even without the application of other anti-bacterial agents and hence can provide complete protection of wounds from skin and soft tissues infections and haemostatic (due to the presence of chitosan). After testing and certification based on IS997:2004 and BS EN 13726-1, they should meet many requirements specified. Anti-bacterial crab bio-bandages should be eligible for marketing. Some results were as follows: 1.4 Anti-bacterial effect of crab hydrogels and roasted crab hydrogels Pure chitosan, crab chitosan, crab hydrogels and roasted crab hydrogels showed significant anti-bacterial effect. NO oral bacterial colonies were present in drinking water with crab hydrogels. Thus crab hydrogels could serve as effective anti-bacterial wound dressings. 1.6 Basing on IS997:2004 standard, the load per unit of area of anti-bacterial bio-bandages was 342g/m2 which met the minimum requirement of 36g/m2, the anti-bacterial bio-bandages had stronger tension strength (>20N both in dry and wet conditions) than commercial hydrocolloid. (2.7N dry 2.8N wet) which was comparable with that required (50-67N) and pH of about 7 which met the pH range of 4.5-8. 1.7 The FSA Free-Swell Absorbency of synthetic blood of crab hydrogel bio-dressings was 1.86g per 5cm x 5cm dressing which was much higher than that of commercial hydrocolloid (0.299g per 5cm x 5cm dressing) based on BS EN 13726-1.
HOST TARGET PROTEINS OF SPIKE PROTEIN OF SARS-COV-2
Coronavirus Disease 2019 (COVID-19) is a newly emerged infectious disease caused by the new severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV-2). In less than one year, the virus has spread around the entire world, killing millions of people and disrupting travel and business worldwide. During infection, the virus uses its Spike protein to dock onto the Ace2 protein on the surface of its human host cell. Spike is 1273 amino acids long and only a short fragment of Spike (319-541) is sufficient to bind Ace2. We hypothesized that the remaining protein sequences of Spike might have functions for viral replication beyond the binding of Ace2. We have performed Split-Ubiquitin protein-protein interaction screens to isolate human proteins by their ability to bind to Spike, and we have identified Annexin2A2 and Cytochrome b as novel human protein interaction partners of Spike. Annexin2A2 is involved in both endocytosis and exocytosis, and the protein interaction with Spike might help the virus to enter and exit its host cell. The presence of the mitochondrial Cytochrome b protein inside the cytosol promotes apoptosis, and the protein interaction with Spike could speed up sapoptosis of the infected human cell. The Nub cDNA libraries that we have generated also allowed us to screen for synthetic peptides that interact with Spike. We have isolated two synthetic peptides, FL1a and FL7a, derived from the non-coding parts of human mRNAs by their ability to interact with Spike. We found that both FL1a and FL7a interact with the C-terminal half of the Spike protein. We also found that FL7a is able to block the Spike-Spike self-interaction at the C-terminal half of the Spike protein and we think that this could block the reassembly of the Spike protein in the host cell during viral reassembly. We hope that those synthetic peptides could be used as drugs due to their ability to block protein-protein interactions of Spike with human host proteins that are essential for viral replication.