ALPHA- AND BETA-GLOBIN GENE MUTATIONS IN GEORGIA AND ARMENIA.

Georgia and Armenia are situated at the northern rim of the thalassemia belt and bordering to countries with a known high prevalence of thalassemias. In this study we assessed the carrier frequency and potential spectrum of alpha- and beta-globin mutations among 202 and 190 unselected Georgian and Armenian subjects, respectively. We found four alpha-globin mutations (-3.7del, -4.2del, anti-3.7 triplication, poly-A2) in 9 Armenians (4.74%) and 4 Georgians (1.78%). The heterozygous beta-globin codon 8 [-AA] mutation was detected in one individual from Armenia only. Overall, carrier frequencies seem to be low in both countries, supporting the notion that thalassemias are not a major health problem there.

PECULIARITIES OF NUTRITION AMONG MEDICAL UNIVERSITY STUDENTS.

Healthy nutrition helps to prevent development of chronic diseases and contributes to optimal functioning of the body. Dietary habits mainly are being established during the late adolescence and young adulthood. Aim - to study nutritional habits of the medical university students in Georgia. A questionnaire containing 73 questions was developed in English and Georgian. Sampling frame consisted of students of the 1st and 4th years of the Tbilisi State Medical University (TSMU). Random cluster sampling was used and total number of participants was 427 (34.4% male and 65.6% female). Mean age 20.6±1.9. Cross-sectional study was performed. The survey was anonymous and self-administered. Principles of Declaration of Helsinki were followed. Data analysis was done in Stata 14.0. Majority of the respondents have 3-4 meals a day and have hot meals several times or once a day. 193 (45.20%) refuse drinking alcohol at all. 112 (26.23%) almost never eat breakfast. 196 (45.67%) of the students get up at nights to eat. 233 (54.57%) do not consume meals at regular times. 183 (42.86%) do snack between the meals. 326 (76.35%) read or watch TV while eating. 190 (44.5%) eat white bread once a day or few times a day; 102 (23.89%) never eat buckwheat, oats. 326 (76.35%) add sugar to tea or coffee; 231 (54.10%) add salt to the already cooked food. 97 (22.71%) never eat fish. 166 (39.11%) and 172 (40.28%) correspondingly eat red meat and white meat 1-3 times per month or once a week. Only 159 (37.24%) eat fruits once a day or few times a day. 61 (14.29%) and 69 (16.16%) never eat correspondingly raw and cooked vegetables. Our findings are more or less in line with available international data. We think that the situation is similar in the non-medical students and the youth, in general. It might be advisable to perform additional investigations in this direction.

SURVEY OF PRACTICES, KNOWLEDGE AND ATTITUDE CONCERNING ANTIBIOTICS AND ANTIMICROBIAL RESISTANCE AMONG MEDICAL UNIVERSITY STUDENTS.

Antimicrobial resistance (AMR) has become a global problem and is considered an emerging threat to public health worldwide. Aim - to assess knowledge, attitude and practice (KAP) regarding antimicrobial resistance and antibiotics among medical students in Georgia. KAP questionnaire containing 50 questions was developed in English and Georgian. Sampling frame consisted of students of the 4th year of the Tbilisi State Medical University (TSMU). Random cluster sampling was used and total number of participants was 212 (31.13% - International Faculty of Medicine, 45.75% - Faculty of Medicine, 23.11% - Faculty of Public Health). Mean age 22.95 (sd=0.52) with almost equal gender distribution. Cross-sectional study was performed. The survey was anonymous and self-administered. Principles of Declaration of Helsinki were followed. Data analysis was done in Stata 14.0. 79.25% think that antibiotics can cure bacterial infections, 57.08% think that antibiotics can not cure viral infections (statistically significant difference by faculties p<0.0001). 34.43% think that bacteria cause common cold and influenza (by gender p=0.01 and by faculties p=0.03). 83.02% have heard of antibiotic resistance (by faculties p<0.0001). 83.96% agree that antibiotics resistance has become a problem. 75.00% agree that the abuse of antibiotics has become the main cause leading to bacterial resistance. 60.38% consider that antibiotic resistance affects them and their family's health. 93.40% agree that it is necessary to get more education about antibiotics. 31.61% of the students in Georgia always and often stop taking antibiotics if they start feeling better. 43.40% never keep the remaining antibiotics. Obtained results are in line with the international findings. There was seen a statistically significant difference between public health and medical faculties (both English and Georgian) in responses on knowledge. In the attitude and practical behaviour sections all three groups provided similar results, only some questions were provided significantly different responses by faculties.

THE GLOBAL POINT PREVALENCE SURVEY (PPS) OF ANTIMICROBIAL USE AND ANTIMICROBIAL RESISTANCE AMONG HOSPITALIZED CHILDREN IN GEORGIA.

The aims of our study were to determine antibiotic prescribing rates for prevention and treatment of infections in pediatric units, to evaluate the number and type of antimicrobial agents and administration route, reveal commonly used antibiotic subgroups and identify targets for improving the quality of antimicrobial prescribing. A 1-day PPS (Point Prevalence Study) on antibiotic use in hospitalized children was performed in Georgia from 2015 to 2019. 18 clinics in different regions of Georgia were included in the survey. Antimicrobial prevalence rates increased over the years from 60.1% in 2015 to 92.6% in 2018. The most commonly, antibiotics were prescribed for lower respiratory tract infections (LRTI). In 2015 25.1% of LRTI were treated by ampicillin-sulbactam but the next year it replaced with ceftriaxone (37.1% in 2017 and 38.2% in 2018). In pediatric surgical ward, the antibiotics were commonly prescribed for surgical prevention (54.1% in 2015, 32.3% in 2018). The most common conditions treated with antibiotics in neonates were sepsis (30.1%) and LRTI (45.3%). The most used antibiotic was ceftriaxone (33.3% in 2015). Ampicilin-sulbactam was prescribed in 28.1% of pneumonia case in neonates in 2018. In 2015 antibiotics were mainly prescribed empirically (98.0%). In 2018 resistance of MRSA was 8.1%, and resistance to the third-generation cephalosporin 17.3%. Prevalence rate of antibiotics for prevention and treatment of infection disease in pediatric units increased in 2018. Main feasible targets for optimization of antibiotic prescribing have been identified: high use of broad-spectrum antibiotics in hospitals, high frequency of empirical treatment, rarely performed culture tests, prolonged antibiotic prophylaxis in surgery patients and an alarming raise of resistant strains. The implementation of disease-specific clinical pathways associated with annual PPSs could be a good way to monitor and improve antibiotic prescription patterns in neonatal and pediatric inpatients over time.

[PHYSICAL DEVELOPMENT OF CHILDREN IN ORPHANAGES].

Aim - to define the parameters of physical development of children in orphanages. 72 children (45 boys, 27 girls) without chronic debilitating diseases and condition aged from 1 to 6 years from Tbilisi and Makhinjauri orphanages (Georgia) were assessed. Height and weight of all subjects were measured and BMI, height SDS (standard deviation score) and weight SDS were calculated. Data were compared to the normal values (national data). The retardation of the physical development were seen along almost all findings. The significant differences regarding age and gender were not revealed. The most expressed tendency to delay was expressed in the height of boys, particularly aged 3-5 years. Our data confirm that institution upbringing has a negative impact on the growth of children of 1-6 years of age. In children aged from 1 to 6 years who are healthy but live in orphanages there is a marked tendency to lag behind in physical development, mainly in height. The above-mentioned confirms the opinion about negative impact of upbringing in orphanages on the physical development of children.

Fuzzy approaches in pediatrics.

In this paper we present a review of applications of fuzzy methods in children and adolescence health care. Based on the several examples, available from journal papers, conference proceedings and book chapters we have concentrate ourselves on problems in the pediatrics that have been or can be solved with the help of fuzzy methodology. The paper is organised as follows. In section I we consider the general considerations about fuzzy logic and medicine. Section II considers the basics of fuzzy sets and fuzzy logic, the main methodological approaches for medical practical applications. Section III describes problems and the way of their solving using fuzzy approaches in pediatrics. Conclusions summarise the review in Section IV.

Familial Mediterranean fever in Georgia.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder caused by mutations in the MEFV gene. Carrier rates are known to be particularly high among Sephardic Jews, Turks, Armenians and Arab populations. Our literature survey regarding FMF and MEFV mutations in Georgia revealed a lack of existing studies. We applied multiplex PCR and reverse-hybridization teststrips (FMF StripAssay) to simultaneously analyze twelve common MEFV mutations in DNA samples from dried blood on filter cards, which had been obtained from 202 unselected newborns at various hospitals in Tbilisi, Georgia. We found 30 samples to be heterozygous and one to be compound heterozygous or carrier of a complex allele (two mutations in cis). The carrier rate of MEFV mutations (15.3%) was remarkable. The most frequently observed variants were E148Q (15x), M680I G/C (5x) and M694V (4x). Five other MEFV mutations were found at lower prevalence (V726A, A744S, R761H: 2x each; P369S, F479L: 1x each). Based on these new findings, the awareness for FMF and the availability of appropriate testing should be further promoted in Georgia.

Some personal views on pediatrics and not only...

In the paper there are presented author's personal views on youth education, medical education, child and adolescent physiology, some other common medical and pediatric issues. The role of the physician as an educator of the child is underlined. The pediatrician must be the main advisor to the society, school and family in the matter of youth education, contribute to their optimal self-realization. The importance of moral values, gender peculiarities and cultural codes are emphasized. The imprinting of cultural codes should be considered as a biological basis of patriotism. The effectiveness of the implementation of healthy life style is discussed. The opinion regarding the protection of youth from potentially negative effects on their development and behavior is expressed. It would be purposeful to give more consideration to the fundamental research, particularly to the problem of age-related morphological and functional peculiarities of the growing organism in the conditions of norm and pathology. One should have in mind the importance of research of the combination of harmful factors for the organism. The elaboration of empathic and optimistic attitudes should be considered as the very important goals of medical education. The differential usage of clinical guidelines is discussed. It is mentioned the purposefulness of more wide application of fuzzy logic approaches in medicine. The items of rare diseases, individualized medicine, alternative medicine and bacteriophage therapy are discussed as well.

[Familial Mediterranean Fever in children and adolescents in Georgia].

There are presented preliminary results of the analysis of the materials of the register of children and adolescents suffering from Familial Mediterranean Fever in Georgia. The register was created by the "snow ball" method. For today it contains data on 138 patients, 56 (40.6%) males, 82 (59.4%) females, 86 (62.3%) less than 10 year old, 52 (37.7%) 10-18 year old. Almost in all patients the Armenian roots were revealed, both from maternal and paternal sides. Among the MEFV gene mutations M694V (mainly) and also V726A and M680I were the most common ones.

[Some immunological changes in children with bacterial infections treated with bacteriophages].

The aim of the study was to reveal the possible immunological changes in children with bacterial infections treated with commercial bacteriophage preparations administered per os. In case of medical indications (for treatment or diagnostic) blood sampling was carried out. In serum the antibodies against bacteriophage preparations - phage cocktail components (phages against Staphylococcus, Streptococcus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa) were investigated. The neutralisation reaction was used. There were processed samples from 65 children with following diagnoses: sepsis, bacterial pneumonia, urinary tract infection, bacterial infections of upper respiratory ways, bacterial diarrhea. In samples taken in the first days of treatment antibodies were revealed in infants up to one month (I group) in 0/29 cases - 0%, in infants aged from one month till one year (II group)- 1/25 - 4.0%, in children aged from 1 till 15 years (III group) - 3/9 - 33.3%; data after 14-20 days from the beginning of treatment - I group - 0/9 - 0%, II group - 4/15 - 26.7%, III group - 5/5 - 100%; data after 30-60 days from the beginning of the treatment - I group - 1/5 - 20.0%, II group - 6/10 - 60.0%, III group - 3/3 - 100%. Bacteriophages neitralisation degree varied between 50,7% and 97.3%. Any regularity regarding different components of used phage preparations was not established. In case of inclusion of commercial phage preparations administered per os in the treatment of bacterial infections in children, the anti-phage neutralizing antibodies are produced by the macroorganism. This fact limits the duration of phage therapy and its usage in the treatment of future bacterial infections in treated patients. Production of anti-phage antibodies in young infants is substantially less expressed and this indicates to purposefulness and presumably higher efficacy of bacteriophage therapy in this age period.

[Per os given bacteriophages changes the clinical course of diseases caused by bacterial agents in children].

The aim of the study was to reveal the possible effect of perorally given bacteriophages on the clinical course of diseases caused by infectious agents in children. The complex therapy with inclusion of bacteriophages was performed in 85 children aged from 1 week to 15 years, 36 girls, 47 boys with following diagnoses: sepsis, bacterial diarrhea, urinary tract infections, bacterial infections of upper respiratory ways, bacterial pneumonia. For every case an appropriate analoguous control was matched. Thus this open clinical trial was carried out according to the Case Control Study design. Clinical and paraclinical markers specific for different diseases and integrated index of the gravitidy of condition. defined by the method of multicriterial analyzis with usage of Fuzzy logic approaches were revealed in dynamics. It was established that by peroral treatment with commercial bacteriophages the positive trends of investigated parameters had place. The improvement of the integrated index of gravitidy was most pronounced. We suppose that obtaining of more convincing evidences of the clinical value of bacteriophagetherapy the further studies in the more number of patients with the usage of the generally accepted double blind method should be conducted.

Capillaroscopy and ECG parameters in children and adolescents with diabetes mellitus type I.

AIM OF THE RESEARCH: Evaluate ECG parameters and detect changes in capillaroscopy parameters in children and adolescents with Diabetes mellitus type 1 (DMT1). ECG and capillaroscopy were performed in 32 children and adolescents (6-15 years old, 17 boys,15 girls) with DMT1. Disease duration - less than 2 years -13, 2-4 years - 10, 5-10 years - 9 cases. The patients were divided into two groups: I group - 12 patients with no complications of DMT1 (in all them duration of disease was less than 2 years), II group - 20 patients with diagnosed cardiac complications of DMT1 (diabetic cardiomyopathy, angiopathy). Additionally 6 of them had diabetic encephalopathy , 4 - diabetic encephalopathy and peripheral neuropathy, 4 - nephropathy and retinal antipathy. Level of glycosides hemoglobin was 8-11%, level of glucose 4 to 15 mmole/L. Control group included 20 healthy children of the same age. In group I ECG is less informative. Hypertrophies of left ventricle and atrium and disorders of repolarization were mainly found in group II. In 62.5% of cases rhythm and conduction disorders were revealed, which were more often in group II. Capillaroscopy changes (pale and cyanotic background, decreasing of the number of capillaries in sight, dilated and contracted diameter, pathological shape and order of capillaries, slow blood flow) were seen both in I and II groups with more prevalence and intensity in the latter one. In children and adolescents with Diabetes mellitus type 1 ECG and capillaroscopy should be performed on the regular basis in order to reveal early changes and start the appropriate treatment in time.

Assessment of anthropological, physical and functional indices in sportsmen (basketball players) against the background of high physical loading.

The goal of the investigation was the estimation of functional condition of anthropometrical, physical and cardiovascular system of sportsmen-basketball players against the background of high physical loading. 100 basketball players at the age from 12 till 18 years underlay the study. Randomized and open controllable research was carried out during 6 months. The following characteristics have been studied: how many days the sportsman is training in a week, how many hours the sportsman is training per day, his mood after training, over fatigue and overtension, frequency of heartbeat, time of breath holding, the general condition, the height in sitting and standing position; circumference of lumbus, chest, arm and limbs, the pulse, pulse, systolic and diastolic arterial pressure before and after physical loading. According to these factors the following sport indices are calculated: Index of Rufe (physical work capacity), the coefficient of endurance (Kvas formula), Shtange test (breath holding at sighing), Genchi test (breath holding at exhalation), average arterial pressure, systolic and cardiac output of blood circulation (the formula of Lilienstrad and Tsander), the coefficient of blood circulation effectiveness, Ketle index (the ratio of height and weight), Minuvre index (the ratio of body and feet length), Pinie index (power of body-build). Statistically authentic increase of breath and pulse in frequency was observed in sportsmen-basketball players after physical loading. The study of amplitude parameters of cardiac cycle among sportsmen-basketball players before and after physical loading has revealed the ability of rather low adaptation of cardiovascular system to physical loading.

[Characteristics of heart rate variability in healthy adolescents and male adults].

The primary purpose of the present article is to investigate the comparative characteristics of heart rate variability in healthy adolescents and male adults. The study was carried out on 41 male adolescents aged 15-16 years and 73 male adults aged 18-22 years. For assessment of heart rate variability statistical data of variability and spectral analysis of heart rate were estimated. Achieved results have proved once again that vegetative balance in healthy individuals is not identical that can be explained by various physiological processes of adolescent age. Such start conditions probably may affect the character of body response to different stimulative impacts. The study suggests that adults tend to have the prevalence of sympatic regular mechanisms whereas in mature age the cases of individuals with the balanced vegetative nervous system in quiescent mode without pathologies are much more frequent.

[Blood biochemical changes in maternally deprived children and their emotional status].

Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation in animals consisting of a single 24-h maternal deprivation episode during early neonatal life has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. The aim of the present research was to show the mechanisms how the early maternal deprivation in humans influences the emotional status of children. To understand the effects of early deprivation on the regulation of the hypothalamic-pituitary-adrenal axis of children following social interactions, we examined the blood neurotransmitters levels (Norepinefrin NA; Dofamin DF; Serotonin SE) in a group of healthy institutionalized children at age from 6 to 36 months from Tbilisi Infant's House. A group of healthy children of the same age from Mother & child shelters formed the control group. Emotional status was assessed by Leusher's Color Test in a group of healthy institutionalized children at age from 3 to 6 years from Tskneti Orphanage. Institutionalized children showed elevations in blood NE and decreased SE and DF concentrations in comparison with non deprived children's blood. The higher was percentage of children with high level of anxiety in the group of children from orphanage than in the children with family care. The results suggest that early maternal deprivation may contribute to long-term regulatory problems of the stress-responsive system that may be resulted in altered emotionality and behavior in deprived children.

[What happens when the child gets bacteriophage per os?].

The aim of the work was to define the distribution of phages administered per os to children for medical reasons, and the immune response. 102 children aged from 5 days to 15 years with different diseases of bacterial etiology (pneumonia, sepsis, urinary infection, pharyngitis/sinusitis, enteral infection) were monitored. Pyobacteriophage was being included into the complex therapy. The drug was administered per os. In 6/7 of blood, 48/55 urine and 64/75 stool samples taken on the 3-5th day of treatment different components of pyobacteriophage were revealed. The titers varied from 103 to 105 pfu/ml. No age differences were seen. In two weeks after the onset of the phagotherapy the antibodies to phages were tested in the blood serum using the neutralization reaction method. The blood samples were taken from 31 patients. In 14 of them the antibodies neutralizing 52.5-97.3% of the phage activity were seen. A significant age-related peculiarity was determined: in newborns and infants the antibodies were not revealed or their activity was low. Obtained results confirm the reasonability to use of peroral phagotherapy in gastro-intestinal infections. At the same time it was ascertained that the phages taken per os can permeate into the internal environment of the organism and thus the peroral phagotherapy can be used to treat systemic infections and urinary tract infections as well. Absence or low production of the antiphage antibodies in newborns and infants suggests high efficacy of the phagotherapy in this age group.

Management options for rare diseases in children and adolescents in Georgia (experience of the country with transitional economy).

We present the results of our research and organizational work aimed at the management optimization for the rare diseases in Georgia (the Country with Transitional Economy). We compiled a list of the rare diseases actual for Georgia; elaborated algorythms and expert systems supporting the diagnosis making process for various clusters of the rare diseases; translated into Georgian and adapted textual materials regarding the management of various rare disorders; assessed the awareness level for the rare diseases of the pediatricians and general practioners in Georgia and attempted to raise it by organizing seminars and conferences, including international ones, in various regions of Georgia; elaborated a model of the expert system (based on the fuzzy logic principles) for unmasking the cases suspicious for the rare disease; laid the foundation for the national register of the rare diseases in children and adolescents; elaborated the module for post-graduate education regarding rare diseases; organized the center for the rare diseases.

[University center on rare diseases, as a successful example of the integration of the clinical sector into the system of medical education].

There is substantiated appropriateness of the establishment of the University Center on Rare Diseases. It is indicated that the center could illustrate a successful integration of the clinical sector into the system of medical education. The model of the functioning of center and its regulations are presented. The main topics of the special teaching module on rare diseases for physicians are submitted as well.

[Purposefulness of using fuzzy logic approaches in the rare disease clinical trials].

Different methods being used in the rare diseases clinical trials are examined. There is shown the purposefulness of using fuzzy approaches for such studies. Some advantages of Fuzzy logic methods in comparison with Baysian approach are substantiated.

[Clinical value of changes in red blood cell ultrastructure and energy metabolism in children with cystic fibrosis].

In 42 patients of various age (from 1 month to 14 years) with cystic fibrosis were analyzed ultra structure, level of adenylnucleotides and activity ATP-ase of erythrocytes, in order to characterize their membrane and energy metabolism. The studies revealed the changes in erythrocytes in the cases of cystic fibrosis. In the cases of broncho pulmonary form of cystic fibrosis were detected I and II row echinocytes, cone-shaped erythrocytes, also erythrocytes with reach-through hole in center. At mixed form of cystic fibrosis were detected more changes in erythrocytes than in other forms of this disease. Both cone-shaped erythrocytes were more than in other forms of cystic fibrosis. Also there were detected erythrocytes with holes (round, polygonal) in their center. The results of the study provide a more precise diagnosis, in time correction of disorders and a comprehensive assessment of multiple-modality treatment of cystic fibrosis.