Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the 2019-2022 pandemic, coronavirus disease 2019 (COVID-19). The majority of cases were mild, a quarter of infectious disease cases were asymptomatic during the entire course of the disease, hospitalization was required in approximately 15% of cases; up to 5% of cases required management in intensive care unit. In the case of COVID-19 infection, disseminated intravascular coagulation (DIC - disseminated intravascular coagulopathy) characterized by acute respiratory distress syndrome and episodes of thromboembolism are among the main causes of death. More and more evidence confirm that thrombotic diathesis is caused by multiple disorders of the coagulation system. These disorders also include an obvious increase of D-dimer value, which negatively correlates with a positive outcome of the disease. Investigation of COVID-19-induced or “altered” mechanisms that may lead to the development of coagulopathy is extremely important. From this perspective one of targets is antiphospholipid syndrome. Its clinical manifestation is characterized by a wide spectrum and includes vascular thrombosis, spontaneous abortion, asymptomatic cases and additional manifestations that cannot be explained only by the thrombophilic state. At the same time, the prevalence of asymptomatic cases of APS in the healthy population ranges from 1% to 5%. Thus, taking into account all of the above, it is possible that the increase of antiphospholipid antibodies remains "unnoticed" during acute phase of COVID-19, and SARS-CoV-2 and its vaccines correlate with the production of antiphospholipid syndrome specific antibodies in pre-disposed recovered and vaccinated individuals.

The COVID-19 infection was one of the most important challenges for global health in 2019-2022. Nevertheless, many aspects of the SARS-CoV-2 virus and the infection caused by it have not yet been determined and are still the subject of research. Statistical data about the type of symptomatic manifestation of this infection in different age groups, in patients with chronic diseases, is unfortunately scarce. Georgia is not an exception from the mentioned trend. The project responds to this challenge and aims to determine the clinical symptoms common in the SARS-CoV-2 infected population.

Despite technological and diagnostic progress, oncology diseases are still a major health issue. The treatment and the early diagnostics of oncologic diseases are among global and national healthcare priorities. Several biomarkers are used for screening, diagnostics, prognosis, follow-up and monitoring issues of oncology diseases. Although these biomarkers are far from ideal, the ongoing research activities are focused on revealing targets for early detection of oncogenesis and prognosis in case of oncologic diseases.  

In simple words oncogenesis can be explained as the multi-stage process of normal cell transformation into tumor one. The tumors aren’t homogenous. Some pathologic cells of a tumor (Cancer Stem Cells) are similar to stem cells by the way of expressing specific proteins, although they express the ability of uncontrolled growth, which is unusual for stem cells. We expect, that that the transformation of tissue specific (non-cancer) stem cells to cancer stem cells is initial step of oncogenesis and is associated with:

• Aberrant expression of transcription factors Sox2 and Oct4, as well as PIWI proteins and CTAs;
• Aberrant expression of PIWI proteins ensured aberrant expression (over- or down-expression) of piRNAs.

The project aims to investigate the above-mentioned postulate in an interdisciplinary manner.

Project has been funded by the LEPL Shota Rustaveli National Science Foundation of Georgia within the 2022 Call of State Research Grants for Basic Research.

The project “Medicine and Art” of the Petre Shotadze Tbilisi Medical Academy has been funded in the frames of the 2019 year science population targeted call for applications of the Shota Rustaveli National Science Foundation of Georgia. Project “Medicine and Art” aims set up of the kids university and information of pupils about medical sciences and research activities in this scientific field. In the frames of the above-mentioned kids university the information will be provided to the pupils of the elementary schools graduation classes in an integrative, fun and conspicuous manner. Integration ensures project’s innovative approach. It means synthesis of medicine and art, which is essential for development of the interdisciplinary thinking and review of the existed possibilities; these skills are of utmost importance for the concrete event interpretation. The project is the possibility to arise scientific curiosity among pupils and development of STEM in Georgia.

Students are involved in the project realization
Stomach cancer is one of the most common malignant tumor worldwide. According to the Lauren’s classification two types - intestine and diffuse, are determined. Diffuse type adenocarcinoma is the most malignant version, which includes signet ring cell type. Alteration is due to CDH1 mutation and is manifested only in mucosal layer without macroscopical changes of superficial mucosal layer. Accordingly with the data of performed research, in case of the presence of CDH1 mutation in 100% cases of postoperative material following gastrectomy in situ tumor has been revealed. The tumor size variants were 0.1-10 mm.
The correlation between CDH1 mutation and expression levels of  HER2, oncoprotein P53 and proliferative marker Ki67 isn’t determined till now. The project aims study of the mentioned correlation and peculiarities of CDH1 mutation.

Students were involved in the project realization.
Among the majority of patients with temporal epilepsy are observed interictal emotional and behavioural abnormalities. In frames of proposed project will be studied development and exposure of emotional abnormalities, as well as will be studied neural substrate on an animal-involved experimental model, known as “kindling”. (an animal involved experimental model, which is used in frames of temporal epilepsy research) We suggest, that emotional abnormalities may be actual instinctual behavioural acts, which trigger anti-epileptic neurophysiological mechanisms. Obtained results will be experimentally supported foundation for concluding, that interictal emotional behaviour is possible endogenous mechanism, which is characterised by anti-epileptic effect.

Medicine - The Story Presented by Art

Project has been funded in the frames of Shota Rustaveli National Science Foundation 2021 target grant competition for science popularization
The project "Medicine - History in Art" aims to present the history of medicine through the analysis of works of art in order to raise awareness about the role of science, research and innovation and to interest young generations in science. Sketches of Leonardo da Vincis anatomical studies are well known, although themes of infectious diseases, epidemics and vaccinations, medical procedures, and physicians professional clothing occupy a special place in the painting. Salvador Dalis paintings may have correlations with biotechnology. In addition, works of art represent individual physicians, patients, clinics, anatomical theaters, wards, or physician consultation scenes, and often by analyzing the characteristic features of characters represented in works of art, a specific disease can be identified. The frescoes of the palaces of Italian aristocrats, paintings of Bosch, etc. are distinguished and interesting in this respect. It is especially important to analyze the bioethical aspects based on the facts presented in the works of art. The presented project will present the mentioned facts and their analysis to the general public in a fun and interactive way.The project is a continuation of the project "Medicine and Art" of Petre Shotadze Tbilisi Medical Academy (SRNSFG 2019 Target Grant Competition for Popularization of Science) and involves organizing a targeted science festival under the auspices of the Childrens University through the following activities: 1. Organizing and conducting a series of popular science lectures; 2. Organizing and conducting a scientific picnic; 3. Organizing and implementing a seasonal school; 4. Organizing and conducting a scientific conference and makeathon.

In the frames of 2019 Call of State Research Grants for Basic Research, which is administered by the LEPL Shota Rustaveli National Science Foundation of Georgia, have been funded two joint projects with participation of the Petre Shotadze Tbilisi Medical Academy:

"Involvement of ovarian cyst mucins in the production of IgG auto-antibodies cross-reacting with tumour growth factor human chorionic gonadotropin (hCG) and its subunits"
Growing evidence supports the existence of immune-surveillance mechanisms in ovarian tumour patients, including auto-antibodies to tumour associated and tumour specific antigens, tumour growth factors. Glycoprotein hormone human chorionic gonadotropin (hCG) and its hormone-specific hCGβ have been associated with epithelial tumours such as bladder, lung, oral/facial, breast, cervical, ovarian, vaginal, prostate, renal and pancreatic carcinomas. It is believed that hCG plays a role of autocrine growth factor for tumor cells. Scientific team reported, that majority of patients, with ovarian cyst, but not those with ovarian carcinoma had significantly elevated levels of serum auto-antibodies of IgG isotype against hCG and its subunits. They further demonstrated, that these auto-antibodies predominantly belong to the IgG2 subclass and it is plausible that they cross- bind to sugar side chains of hCG and its subunits, but originally are elicited against other glycoproteins. Ovarian cyst fluids constitute one of the richest sources of blood group mucins. Scientific team proposed, that protective auto-antibodies detected in patients with ovarian cysts are cross-reacting with hCG and its subunits through their sugar chains, but are elicited against oligosaccharides of blood group mucins produced by the ovarian cysts. The project aims to check this hypothesis and to investigate whether naturally-occurring in the sera of patients with benign ovarian cysts IgG auto-antibodies to hCG and its subunits, cross-react with ovarian cyst fluid mucins.

"Discovery and understanding role of epigenetic alterations in patients with hematological malignancies residing in Country of Georgia a region affected by Chernobyl explosion"
Although global deaths caused by different types of cancer have been declining, managing this devastating disease remains challenging, particularly in our country Georgia, which is situated, approximately 1448 km from the site of the Chernobyl nuclear power plant accident, which occurred in 1986. Food products and manufactured goods were shared and distributed among those 15 republics including Georgia. All these factors contributed to the exposure of Georgians to low-dose radiation. A decade after the Chernobyl nuclear power plant accident, an increased incidence of hematological malignancies, including multiple myeloma (MM) was observed among people residing in the contaminated region. While the effects of radiation on DNA are widely studied, radiation can also damage RNA through alteration of RNA processing mechanisms. Our long-term interest includes, but is not limited to, understanding the broad effects of low-dose radiation on transcriptome changes through epigenetic mechanisms, including its effects on RNA splicing and its regulation. To achieve goals, scientific team will explore the effects of low doses of radiation on RNA splicing in GE Pts (Georgian patients with hematological malignancies multiple myeloma (MM)) for the following reasons: (1) an increased incidence of MM has been reported in the region affected by the Chernobyl accident; (2) their ongoing studies that monitor alterations in the transcriptome of patients with MM showed a significant impact of splicing alterations on the overall clinical outcome for these patients; and (3) the fundamental role of RNA splicing in human biology and its relevance in cancer are among the most unexpected and dramatic findings that have arisen from the cancer genome sequencing project. The hypothesis of this application is that Georgian MM patients (GE Pts) exposed to the Chernobyl accident may have acquired transcriptome changes through epigenetic alterations, with particular emphasis on altered RNA splicing. To test hypothesis: (1) scientific team will determine the RNA splicing signature in GE MM Pts and (2) identify the cause of altered splicing in these patients. In taking these approaches their studies will identify selective genetic alterations in GE MM Pts and will lead to the identification of novel biomarkers and drug targets, consequently providing unique therapeutic possibilities for these patients.

MoCa and IADL data correlation in individuals with mild cognitive impairment
Young Researcher: Nino Shiukashvili
Montreal Cognitive Assessment (MoCA) test has been shown to be a reliable tool to detect mild cognitive impairment (MCI). In 2015 the indicated tool was translated in Georgian and the consequent validation was conducted (Janelidze, 2016). Besides, the randomized population study (N=1000) was conducted in order to estimate the prevalence of mild cognitive impairment (MCI) in Georgia (Nadareishvili, 2018). Based on this study, the prevalence of any MCI was 13.3% and it was widely associated with the age (>65), with the level of education, hypertension and diabetes. The main indicators are similar to studies in Europe and US. Besides, there are some studies underlying the positive correlation between Mild Cognitive Impairment (MCI) and Instrumental Activities of Daily Living (IADL) (Katrin Jekel, 2015). Based on these studies, IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits.

Projects Funded in the Frames of 2019 Call of State Research Grants for Basic Research Results

MoCa and IADL data correlation in individuals with mild cognitive impairment
Young Researcher: Nino Shiukashvili 
Montreal Cognitive Assessment (MoCA) test has been shown to be a reliable tool to detect mild cognitive impairment (MCI). In 2015 the indicated tool was translated in Georgian and the consequent validation was conducted  (Janelidze, 2016). Besides, the randomized population study (N=1000) was conducted in order to estimate the prevalence of mild cognitive impairment (MCI) in Georgia (Nadareishvili, 2018). Based on this study, the prevalence of any MCI was 13.3% and it was widely associated with the age (65+), with the level of education, hypertension and diabetes. The main indicators are similar to studies in Europe and US. Besides, there are some studies underlying the positive correlation between Mild Cognitive Impairment (MCI) and Instrumental Activities of Daily Living (IADL) (Katrin Jekel, 2015). Based on these studies, IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits.

Analysis of Health Sector Response to COVID-19 Pandemic in Georgia, Armenia and Slovenia
The pandemic known as COVID-19 has completely isolated countries, disrupted health systems and paralyzed the world. A reported outbreak of pneumonia caused by an unknown source in the Hubei province of China was reported in late December 2019 (WHO, 2020). The source has since been identified as a betacoronavirus similar to Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV). It has since been named SARS-CoV-2 and has caused the emergence of the coronavirus disease 2019, referred to as COVID-19.
On 30 January 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern, and then subsequently, a pandemic on 11 March 2020 (WHO, 2020). In the first six months of 2020, COVID-19 has affected almost all countries and eight million people around the world. The action plan of the governments and their health sectors to fight the pandemic is heterogeneous, many countries have been quite unprepared to fight the pandemic and manage the crisis, and many of them have met the challenges with prompt response and appropriate regulations. It is essential to have the worldwide studies of pandemic development and ongoing activities be conducted on an ongoing basis to analyze and identify the next steps in both to fight against the coronavirus pandemic and the management of similar crises expected.

Cervical cancer screening in Georgia, benchmarking on the example of the Czech Republic and Lithuania
Young Researcher: Gvantsa Dadiani
At the end of 2013, 1537 women were registered in Georgia, diagnosed with cervical cancer. However, according to the Cancer Registry, the incidence of cervical cancer in 2017 per 100,000 women decreased significantly after the increase observed in 2015-2016. Only 1 case of the disease was detected in the age group under 25 years. According to the same registry, the diagnostics of new cases of cervical cancer in stages I and II of the disease varies from 52% to 55%, however, it is important to note that the incidence of cervical cancer in Georgia exceeds the average of the European region and CIS countries.
The project aims to conduct an in-depth study in the form of a comparative analysis of available data on the organization and implementation of cervical cancer screening in Georgia and similar socio-economic countries to highlight important points that will allow to formulate some conclusions and develop recommendations  in terms of further effective organization of screening.

Students are involved in the project realization.
Many factors that determine health are known today. A healthy lifestyle and physical activity are among these factors. It is well known that most chronic illnesses are caused by lifestyle. For example, smoking, malnutrition, lack of physical activity, excess alcohol or drug use. Based on the fact that an unhealthy lifestyle quickly leads to stress, bad moods, self-esteem problems, and easy fatigue, a healthy lifestyle is of particular importance to the students, and it is necessary to educate the students population about the positive effects of a healthy lifestyle, which can have a significant positive effect on the health. The research design used cross-sectional research. The self-assessment questionnaire will survey about 600 students from 18 to 25 years of age from medical and non-medical faculties of Tbilisi -Georgian. Statistical analysis and comparison of the obtained data will be done after obtaining the surveys result. The threefold goals of the study are to identify the distribution of healthy lifestyles among the student population, to identify key problem related to the lifestyle among the student population, and provide recommendations for implementation of healthy lifestyles and practices focused on problem solving.

Students are involved in the project realization.
The main aim of the project is to identify naturally occurring autoantibodies in the female patients with ovarian cysts during the reproductive ages. The first results of our experiments indicate that patients with ovarian cyst have significantly elevated levels of naturally occurring serum antibodies of IgG isotype against both hCG and hCGb, whilst patients with ovarian carcinoma expressed non appreciable levels of such antibodies. Based on this information we propose that naturally occurring autoantibodies have regulatory, protective role against the malignisation of ovarian cysts. We hope, that autoantibodies that have inhibitory or protecting effects could lead to the development of tumor prevention and treatment strategies. Evaluation of naturally occurring autoantibodies against hCG in patients with ovarian cysts.

Project has been realized by participation of students registered for the teaching course "Biochemistry 3".
Oncology diseases and their treatment are the priority tasks of healthcare. The cancer critical genes are already determined, but genes responsible for development of metastasis and cancer recurrence are not identified till present.
FOXP3 (Forkhead box protein P3) gene is one of the candidates. The expression of the mentioned gene in tumor cells has been determined experimentally (Ebert et al., 2008; Karanikas et al., 2008; Takenaka et al., 2013). FOXP3 gene is located in the short arm of X chromosome. It is coding transcription factor and is characterized by the complicated mechanism of gene expression. FOXP3 gene’s expression in tumor cells ensures the development of immunosuppression (Hinz et al., 2007; Cuncha et al., 2012; Waight et al., 2015) through the transformation of regulatory T cells to Tregs (Liyanage et al., 2006; Li et al., 2007; Yuan et al., 2011). It is known, that presence of Tregs in tumor tissue is associated with poor prognosis (Adeegbe et al., 2013; Ondondo et al., 2013; Sahin et al., 2013).
The intensive expression of SOX2 and OCT4 genes in tumor cells is also important from the point of molecular mechanisms of metastasis (Xu et al., 2017; Ayob et al., 2018). These genes belong to the group of genes specific to stem cells. They are coding transcription factors those activity is important for embryonal development and formation of different tissues. Therefore, expression of SOX2 and OCT4 genes in tumor tissue correlates with the concept of cancer stem cells. Accordingly with this concept neoplastic growth is similar to the renewal of normal tissue and is ensured by stimulation of cancer stem cells. Furthermore, the presence of cancer stem cells in tumor tissue has been determined experimentally (Batle, 2017).
Taking into account all above mentioned, we propose that intensive expression of FOXP3 gene is the molecular pre requisite of metastasis development and ensures activation of SOX2 and OCT4 genes.
The aim of the proposal is experimental provement of the above mentioned scientific hypothesis.

Students are involved in the project realization.
Presented project aims to investigate different forms of memorising and learning processes among 2 groups of animals. Experimental group of animals, which will include subjects with immunotoxin induced damages of cholinergic and GABA-ergic neurones, will be compared to the control group of pseudo-operating subjects. Aside of it, project aims to identify changes, induced by the memory deficiency associated structural changes and neurotransmitter markers (cholinergic α7 nAChRs and M1 and glutamatergic GluN2B subunit containing NMDA receptor expression ) within the selected locations of cortical areas.  
Such multidisciplinary research on systematic, structural and molecular levels creates a prerequisite for obtaining new information regarding modulating functions of basal forebrain within memorising processes and enables us to determine causal relationship between forebrain, and function of internal networks in selected locations within the processes of memorising and learning.
Recognition of basal forebrain modulating mechanism on memory, as well as determining aspects of memory, where this system has high importance, would facilitate understanding of fundamental neurobiological mechanisms of the memory and elaborating new strategies for improvement of memory among patients with neurodegenerative diseases. Study of Nucleus Basalis of Meynert (NBM) role within memorising and learning processes on the behavioural, structural and molecular levels.

Students were involved in the project realization.
According to World Health Organization (WHO) data, every year approximately 2 billion people are affected by intestinal infections all over the world. Foodborne and waterborne pathogens continue to be one of the major causes of morbidity and mortality, and they also cause significant morbidity in developed nations and lead to about 1.8 million deaths globally every year. Due to these problems microbiological and molecular-biological investigation of bacterial pathogens, causing intestinal infections is very important. One of the major food and waterborne pathogens are different species of Salmonella, Shigella and pathogenic Escherichia coli.
As reported by the National Centre for Disease Control of Georgia about 60 000 cases of intestinal infections and 30 000 presumptive infectious diarrheal diseases are identified every year in Georgia.
Monitoring and control of foodborne and waterborne pathogens will reduce their occurrence in the environment and food line and therefore the risk of spreading diseases caused by these pathogens will also decrease.
Because of the unique resistance patterns of bacterial strains to antibiotics, the determination of sensitivity to antimicrobial preparations is very important for monitoring of pathogens and can be used as a necessary epidemiological marker for these pathogens.
The aim of the project is to identify bacterial pathogens causing intestinal infections in clinical specimens, as well as food products (meat, eggs) and water samples and to determine the sensitivity of isolates strains to antibiotics.
To achieve this goal, the following actions will be performed:

• Isolation and identification of bacterial pathogens causing intestinal infections from clinical samples using morphological, biochemical, and serological methods;
• Isolation and identification of bacterial pathogens causing intestinal infections from food products and water samples using morphological, biochemical, and serological methods;
• Investigation of antibiotic resistance profiles of isolated strains. Investigation of Foodborne and waterborne bacterial pathogens causing gastrointestinal tract infections.

Cancer testis antigens (CTAs) are proteins those are predominantly expressed in adult testis and silenced in most somatic tissues. Most CTAs genes are located in clusters at chromosome X, whereas others exist as autosomally encoded single genes. The name CTAs implies that these proteins are mainly specific to male germline. Although they are expressed in females too. It has been revealed that the pathologic expression of CTAs correlates with the chromosomal structural abnormalities and instability. The project aims to determine the expression of CTAs in oncology diseases and the possible mechanisms of their reactivation.

The aim of this proposal is to detect the presence of an autoimmune response in patients with COVID- 19 (without the history of the autoimmune rheumatic disease) by determining antibodies against cell free DNA, myeloperoxidase, cathepsin S and complement type 2 receptor. The data obtained are important for assessment the role of COVID-19 infection as an etiological factor in the development of autoimmune rheumatic disease and, development of an effective approach of early diagnosis.