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Day 1 full schedule

September 23, 2020 @ 10:00 - 12:55

Molecular bases for pharmacotherapy of COVID-19

Anna Sh. Archvadze

Anna Sh. Archvadze

Associate Professor

David Tvildiani Medical University

Georgia

ABSTRACT

The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus has become a global threat. As of 19 August 2020, the pandemic caused an accumulation of 1 351 confirmed cases and 17 deaths in Georgia, and 22 334 752 confirmed cases, and 784 875 deaths in 213 other countries worldwide. The mortality rate is high in patients with comorbidities of Cardiovascular Diseases (13.2%) and Diabetes Mellitus (9.2%). COVID-19 is caused by the newly emerging severe acute respiratory syndrome (SARS) related coronavirus species 2 or SARS-CoV-2, which binds to the angiotensin-converting enzyme 2 (ACE2) molecule on the host cell membrane via the viral spike protein and expresses complex pathological changes in many organs linked mostly with vasculopathy. Microscopic examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates, indicating Acute Respiratory Distress Syndrome (ARDS). The immune system plays crucial role in tissue damage. Results from flow cytometric analysis demonstrated that the counts of peripheral CD4+ and CD8 + T cells were substantially reduced, while their status was hyper-activated as evidenced by the high proportions of HLA-DR (CD4 3·47%) and CD38 (CD8 39·4%) double-positive fractions. Moreover, there was an increased concentration of highly pro-inflammatory CCR6+ Th17 in CD4 T cells. This indicated severe immune injury in later stages of COVID-19, but not by virus direct destruction. In the same time coagulation function disorders were reported in most of the severe COVID-19 patients (in Wuhan more than in 20% of patients), by elevated levels of D-Dimer and prolonged prothrombin time, some of whom ended in disseminated intravascular coagulation (DIC) deep venous thrombosis (DVT) or fatal pulmonary thromboembolism (PTE). At the later stage we have results of thrombocytopenia as a result of excessive platelets consuming, which significantly affects treatment and prognosis. At this moment potential treatments included Remdesivir, Hydroxychloroquine, Betamethasone, Tocilizumab, anti-HIV drugs, convalescent plasma, and vaccine immunization (when possible). Conclusion & Significance: Our review emphasizes the controversial changes in the immune system as well as in coagulation processes that may play a substantial role in the development and progression of COVID- 19 as well as in the pathogenesis of SARS-CoV-2. Drugs have no significant impact on the ARDS, as well as on SARS-CoV-2. So, we still need new targets and new drugs for the prophylaxes and treatment of COVID-19 even we will have vaccines available.The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus has become a global threat. As of 19 August 2020, the pandemic caused an accumulation of 1 351 confirmed cases and 17 deaths in Georgia, and 22 334 752 confirmed cases and 784 875 deaths in 213 other countries worldwide. Mortality rate is high in patients with comorbidities of Cardiovascular Diseases (13.2%) and Diabetes Mellitus (9.2%). COVID-19 is caused by the newly emerging severe acute respiratory syndrome (SARS) related coronavirus species 2 or SARS-CoV-2, which binds to the angiotensin-converting enzyme 2 (ACE2) molecule on the host cell membrane via the viral spike protein and expresses complex pathological changes in many organs linked mostly with vasculopathy. Microscopic examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates, indicating Acute Respiratory Distress Syndrome (ARDS). Immune system plays crucial role in tissue damage. Results from flow cytometric analysis demonstrated that the counts of peripheral CD4+ and CD8 + T cells were substantially reduced, while their status was hyper-activated as evidenced by the high proportions of HLA-DR (CD4 3·47%) and CD38 (CD8 39·4%) double-positive fractions. Moreover, there was an increased concentration of highly pro inflammatory CCR6+ Th17 in CD4 T cells. This indicated severe immune injury in later stages of COVID-19, but not by virus direct destruction. In the same time coagulation function disorders were reported in most of the severe COVID-19 patients (in Wuhan more than in 20% of patients), by elevated levels of D-Dimer and prolonged prothrombin time, some of whom ended in disseminated intravascular coagulation (DIC) deep venous thrombosis (DVT) or fatal pulmonary thromboembolism (PTE). At the later stage, we have results of thrombocytopenia as a result of excessive platelets consuming, which significantly affects treatment and prognosis. At this moment potential treatments included Remdesivir, Hydroxychloroquine, Betamethasone, Tocilizumab, anti-HIV drugs, convalescent plasma, and vaccine immunization (when possible). Conclusion & Significance: Our review emphasizes the controversial changes in immune system as well as in coagulation processes that may play a substantial role in the development and progression of COVID- 19 as well as in pathogenesis of SARS-CoV-2. Drugs have no significant impact on the ARDS, as well as on SARS-CoV-2. So, we still need new targets and new drugs for the prophylaxes and treatment of COVID-19 even we will have vaccines available.

Adolescent diabetes mellitus-right time to be concerned

Goutam Kumar Acherjya

Goutam Kumar Acherjya

Assistant Professor

Bagherpara Upazila Health Complex

Bangladesh

ABSTRACT

Diabetes mellitus is an endocrine disorder where hyperglycaemia occurs due to defect in insulin secretion, insulin action or both. Recently WHO member countries have given more emphasis on the non-communicable diseases (NCDs) rather than the communicable diseases for the sustainable developmental goal due to increased rate of long-term morbidity, mortality and high cost health related resources expenditure. Diabetes mellitus is one of the four priority NCDs related to both macrovascular and microvascular complications causing blindness, kidney failure, heart attacks, stroke and lower limb amputation. Due to genetic predisposition, environmental factors, positive family history, obesity, inadequate physical activities, sedentary lifestyle, rapid urbanization and unhealthy food practice the global prevalence of diabetes is dramatically increasing not only in the adult and older aged group but also in the children and adolescent aged group. In near future many countries of the globe may face a major public health challenge more than our anticipation due to increased prevalence of adolescent diabetes which is directly related to early onset risk factors and complications. There are high up negative significant effects on the quality of life, employment and health related expenditure when diabetes affects in this age group. So necessary steps and strategic plan should be designed for the earlier detection and intervention of adolescent diabetes.

A public BCR present in a unique dual-receptor-expressing lymphocyte from Type 1 diabetes patients encodes a potent T cell autoantigen

Adebola M. Giwa

Adebola M. Giwa

Pediatric Endocrinologist

Johns Hopkins University School of Medicine

USA

ABSTRACT

Purpose: T and B cells represent two known distinct lineages of adaptive immune cells. They are responsible for the host defense and driving autoimmunity through the recognition of foreign- and self-antigens, using clonally diverse antigen cell receptors, BCRs, and TCRs. This study describes a previously unknown lymphocyte that is a dual expresser (DE) of TCRs and BCRs that is significantly elevated in people with type 1 diabetes (T1D). Methods: These cells have been identified and confirmed with the use of multi-color flow cytometry, flow cytometric imaging (Amnis), and deep sequencing. Its function and properties have been evaluated using vitro stimulation and intracellular cytokine analysis high-speed flow-based sorting. Results: In T1D, DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen-binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. A synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Monoclonal antibodies bearing this clonotype are autoreactive against CD4 T cells. Conclusion: The division of adaptive immune cells into T and B cells is not absolute. DE cells may provide insight into T1D pathogenesis. Utilizing the identical BCR clonotype property in T1D may facilitate earlier identification and stratification of individuals at risk for the disease and help develop targeted immunotherapy to prevent T1D and preserve beta-cell function in new-onset T1D patients.

Study of correlation between fasting salivary ghrelin & fasting blood glucose in type 2 diabetics: A pilot study

Mohammed Jaffer Pinjar

Mohammed Jaffer Pinjar

Associate Professor

Government Medical College Mahbubnagar

India

ABSTRACT

Diabetes is one of the most common disorders which is spreading like rapid fire both in developed & developing countries. Hypothesis: fasting salivary ghrelin (FSG) acts as an independent risk factor for the development of type 2 DM. Ghrelin has shown to play an important role in glucose homeostasis. Many studies have shown that circulating levels of ghrelin are diminished in patients with type 2 diabetes mellitus (DM) and inversely correlated with BMI. Few studies show a negative correlation between FSG levels and FBG levels leading to the pathogenesis of type 2 DM. No studies have done to know the levels of FSG in type 2 diabetics. Objective: To correlate between FSG & FBG in type 2 DM patients. Materials and Methods: Fifteen type 2 DM patients (10 males & 5 females) in the age group of 35-60 years with no complications randomly selected for this cross-sectional study. Exclusion criteria: Any history of cardio-vascular diseases like hypertension, coronary artery disease, metabolic disease like type 1 DM, Metabolic syndrome. Smokers, Alcoholics, any history of respiratory diseases, renal diseases, tumours, CNS disorders, any history of oral cavity disorders, pregnancy & menstrual periods excluded. Institutional ethical clearance obtained before conducting the study.Biochemical investigation of FBG level by Trinder’s method (Glucose oxidase – Peroxidase) & FSG by ELISA method done. Pearson correlation test was done to know the relation between FSG & FBG levels. Result found to be a negative correlation which is highly statistically significant. (r = -0.83, p=0.001). Conclusion: The result of negative correlation between FSG & FBG in the type 2 DM parents suggests that FSG may act as an independent risk factor apart from the other risk factors like obesity etc. This pilot study helps in identifying the FSG as a screening marker in the type 2 DM patients. Increased number of researches should be taken in this field. This research study got approved from ICMR STS project 2019 with the reference id: 2019-00675.

An insight into the mechanistic links between COVID-19 and diabetes

Nagalakshmi CS

Nagalakshmi CS

Professor

Sri Siddhartha Institute of Medical Sciences

India

ABSTRACT

COVID-19 is a rapidly spreading communicable disease worldwide. It varies widely in its spectrum of manifestations, from being mild self-limiting disease, to fulminant disease, often leading to complications and death.1 Diabetes is an important co-morbidity linked to severity of infection by SARS-CoV-2, which predisposes them to severe pneumonia.2 Poor glycaemic control is associated with worse outcomes.3 The disease burden of COVID-19 is continuously increasing, and with a high prevalence of diabetes, it is all the more important to understand the vital aspects of COVID-19 infection in diabetic population. 4 Hence, we try to provide close insights into its pathophysiology, clinical characteristics, recommendations on management and prevention and possible avenues for improving disease outcomes. Three main mechanisms which influence COVID-19 disease manifestation in diabetics include: (a) Entry of virus via ACE-2 receptors (b) Action through Dipeptidyl-peptidase-4, and (c) Elevation of glucose concentration in airways by elevated blood glucose.2,5 ACE-2 is expressed in alveolar epithelial cells, heart, renal-tubular & intestinal epithelia, and pancreas. S-Glycoprotein on the surface of SARS-CoV-2 binds to this ACE-2 and undergoes a conformational change. This allows its’ proteolytic digestion by host cell proteases TMPRSS2 and Furin, leading to internalization of virus. Viral entry into cells trigger an inflammatory response by T-helper-cells and at times, a ‘cytokine storm’, resulting in organ damage.4 Apart from diminishing neutrophil chemotaxis and reducing phagocytosis, by which diabetes predisposes individuals to infections, there are several specific factors with respect to SARS-CoV2: (i) Increased ACE-2 expression (ii) Raised Furin (iii) Diminished T-cell functioning, and (iv) Increased IL-6 levels.4 Movement restrictions, increased stress due to social isolation and lack of physical activity further complicates the issue. It is therefore, much essential to raise awareness among front-line workers. Finally, the current situation emphasizes the need for more clinical investigation and define best practices for optimum outcomes.5

Model of nursing service among patients with non-communicable diseases, King Narai Hospital, Lop Buri, Thailand

Ananya Manit

Ananya Manit

King Narai Hospital, Thailand

King Narai Hospital

India

ABSTRACT

Non Communicable diseases (NCD) such as Diabetes and Hypertension has increased every year in Thailand as other countries in the world. That made the patients were suffered and decreased quality of life. This study of qualitative research aimed to develop a Nursing service model among patients with NCD, King Narai Hospital by using Evidence-based practice (EBP) concept of Soukup (Soukup, 2000).  The sample included 30 patients with NCD--Diabetes, and Hypertension, 15 persons of a multidisciplinary team. The instrument was semi-structure interview of NCD quality clinic that was developed from the standard manual of NCD Clinic Plus of NCD, MOPH, Thailand (2016). The data were collected by NCD situational analysis, interviewed patients with Diabetes, and Hypertension, and multidisciplinary team. Furthermore, the EBP concept of Soukup (2000) was applied to develop a Nursing service model among patients with NCD, King Narai Hospital, Lop Buri, Thailand. Content analysis was implemented for data analysis. The results showed that the nursing service model among patients with NCD, King Narai Hospital that was developed comprising 6 components: directions and policies, information system, system adjustment, and service process, self-management support system, decision support system, and arranging linking service to the community. Conclusion: Nursing service model among patients with NCD that was developed, there were 6 components according to the standard manual of NCD Clinic Plus of NCD, MOPH, Thailand (2016). There was a little word of some component to improve. It will be launched to improve the quality of care among patients with NCD, Narai Hospital, Lop Buri, Thailand, and other areas.

Life style modifications: Perception and Belief

Lal Chandra

Lal Chandra

Director-Professor

Maulana Azad Medical College

India

ABSTRACT

Lifestyle modifications are well needed to prevent many diseases or required to overcome/control many. Despite the best approach adapted so far, has not proven successful. Most of the diseases are linked with genes, which are simply molecular blueprints used in the construction of cells, tissues, and organs. The environment serves as a contractor engaging these blueprints to characterize a cell’s life. Now, the science of signal transaction focuses upon the pathways linking environmental cues, affecting cytoplasmic /cellular processes which can alter gene expression and thereby controlling its fate. The new science of Epigenetics has completely upended our conventional understanding of genetic control. Thorough knowledge and its application will surely enable to understand /prevent/control many diseases.