CHARACTERISTICS OF DIARRHEAL DISEASE COMPLICATED WITH HEMOLYTIC UREMIC SYNDROME AMONG CHILDREN IN GEORGIA, 2009-2016.

Shiga toxin-producing Escherichia coli (STEC) causes illness ranging from mild diarrhea to bloody diarrhea, to the hemolytic uremic syndrome (HUS), which manifests with a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Surveillance of HUS and bloody diarrhea is not performed in Georgia. The primary objective of our study was to determine the annual incidence of diarrheal diseases. The secondary objective was to assess epidemiological characteristics, etiology and risk factors of diarrhea and HUS in Georgia among children under 15. We collected a retrospective data on diarrheal diseases particularly bloody diarrhea and HUS among children in Georgia in 2009-2016 years. Laboratory, clinical and epidemiological data was entered into electronic database. Descriptive statistics, proportions, incidence rates, means and medians were calculated in R statistical language using statistical package R for windows v 3.4.3. A total of 316 cases of bloody diarrhea including 64 (20.2%) cases complicated with HUS under age 15 were identified from 2009 until 2016. From 316 patients 5 (1.6%) have died, all of them with diagnosis and severe complications of HUS. Average rate of HUS per 100,000 populations during 2009-2016 was 0.3 and for bloody diarrhea 2 per 100,000. High RR for food products consumed by children with bloody diarrhea either complicated with HUS or not were various ice-creams produced locally (RR 4.23 P<0.001), dairy products (RR 2.79 P = 0.01), ground beef products (RR 4.52 P<0.001). The another highest attack ratio was identified for fruits (RR 6.19 P<0.001) and vegetables (RR 3.45 P < 0.001). Different enteric pathogens including shiga toxin producing E. coli was detected as etiology of diarrheal diseases and HUS. Epidemiological data suggests that inadequately washed fruits, vegetables and eating undercooked food and ice-cream could be a possible risk factors of exposure with enteric pathogens and developing diarrhea and HUS among children. Further investigations of food products are required to determine epidemiology and source food products of bloody diarrhea and HUS among children in Georgia.

IMPACT OF SULPHUR DIOXIDE ON THE RESPIRATORY SYSTEM OF TBILISI POPULATION.

The possible relationship between levels of sulphur dioxide (SO2) in the air and the rate of respiratory diseases has been studied. Results of monitoring of main contaminants of outdoor air were analyzed and they are reflected in Environmental Report 2015. Information on morbidity by respiratory system diseases of Tbilisi population is has been taken from 2011-2015 reports of the National Center of Disease Control. Identified that there is no consistent correlation between sulphur dioxide concentration in the air and respiratory system disease rates in the population, including children. Obtained data demonstrated that during the study period maximum SO2 concentration was registered in 2015 - 0,14 mg/m3 (exceeding almost 3 times maximum permissible concentration - 0,5 mg/m3) and in the same year high morbidity rates are registered (incidence -18106,08), though the lowest rates are registered in 2011 (0,09 mg/m3), when incidence of respiratory system diseases in this period (13103.2) exceeds the rates registered in 2012, 2013 and 2014 (12736.4, 11336.3, 13009.0 accordingly). There is no direct correlation between the morbidity rates of 0-15 year old children and SO2 concentration. Maximum incidence rate is registered in 2015 (48487.0) and in the same year is also registered maximum concentration of SO2 (0,14 mg/m3), whereas the lowest rate is registered in 2013 (35538,70), when SO2 concentration in 2013 is lower only by 0.02 mg/m3 compared to the concentration in 2015. Direct correlation between morbidity with asthma in children and concentration of SO2 was not identified. Prevalence of asthma is minimal in 2014 (65,4), maximal in 2012 (207,1), whereas SO2 concentration in 2014 (0,13 mg/m3) exceeds the concentration in 2012 (0,12 mg/m3). It has to be considered, that besides SO2 there are many small intensity adverse factors, which are also risk factors for development of respiratory diseases. Isolated action of these factors with certain concentrations may not demonstrate any adverse effects on human health, but the combined effect of their action is stronger and obviously will affect general health and specifically - respiratory system. Implementation of urgent measures for further improvement of their ambient air quality has been recommended, which will be the basis for minimizing of many chronic diseases.

Active surveillance of African swine fever in domestic swine herds in Georgia, 2014.

Since its introduction to the Republic of Georgia in 2007, African swine fever virus (ASFV) has spread across the Caucasus region, the Russian Federation, and some Eastern European countries. It is assumed that large populations of naïve, domestic, free-ranging and wild pigs are vital to the transmission of the disease. Since its epidemic emergence in the region in 2007, ASFV has continued to circulate, which suggests that an endemic cycle has been established and is maintained by contact between free-ranging domestic pigs, wild pigs, and possibly native Ornithodoros ticks, the most likely reservoirs for the virus. In 2014, a survey was conducted across the Republic of Georgia to determine ASFV prevalence among domestic swine herds. All 1,231 samples collected for this survey tested negative for ASF. The probability of observing no reactors in a sample of this size (n = 1,231) from a population with an estimated disease prevalence of 1% is very low (<0.0001). Therefore, it is possible but very unlikely that ASFV was present among domestic swine during the span of this survey. These data suggest that, in 2014, domestic pig herds were not the source of the virus, and that the ASF endemic cycle may be supported by the circulation of ASFV among feral pigs, wild pigs, and possibly native Ornithodoros ticks.

Depuis son introduction en république de Géorgie en 2007, le virus de la peste porcine africaine s'est propagé dans toute la région du Caucase, dans la fédération de Russie et dans certains pays d'Europe orientale. On estime que la transmission de la maladie nécessite des populations naïves et nombreuses de porcs domestiques, élevés en liberté et sauvages. Depuis son émergence épizootique dans la région en 2007, le virus de la peste porcine africaine a continué de se propager, ce qui semble indiquer qu'un cycle d'endémicité s'est établi et se maintient par contact entre les porcs domestiques en liberté, les porcs sauvages, et vraisemblablement les tiques autochtone du genre Ornithodoros, le réservoir le plus probable du virus. Une enquête a été effectuée en 2014 sur tout le territoire de la république de Géorgie afin de déterminer la prévalence du virus de la peste porcine africaine au sein des troupeaux de porcs domestiques. La totalité des 1 231 échantillons prélevés à cette fin ont donné des résultats négatifs au test de détection de la peste porcine africaine. La probabilité qu'un échantillon de cette taille (n = 1 231) ne donne aucune réaction positive dans une population pour laquelle la prévalence de la maladie est estimée à 1 % est extrêmement faible (< 0,0001). Par conséquent, la présence du virus de la peste porcine africaine chez les porcs domestiques au cours de la période de l'étude est possible, mais très peu probable. Ces résultats suggèrent que le cheptel de porcs domestiques n'a pas été à l'origine du virus en 2014 et que le cycle d'endémicité de la maladie est davantage soutenu par la présence du virus chez les porcs féraux et sauvages ainsi que probablement chez les tiques autochtones du genre Ornithodoros.

Desde que en 2007 penetró en la República de Georgia, el virus de la peste porcina africana se ha extendido por toda la región del Cáucaso, la Federación de Rusia y algunos países de Europa Oriental. Se presupone que, para que haya transmisión de la enfermedad, se requieren grandes poblaciones de cerdos sin exposición previa, domésticos, criados en libertad y salvajes. Desde su aparición epidémica en la región, en 2007, el virus de la peste porcina africana ha seguido circulando, lo que lleva a pensar que se ha arraigado un ciclo endémico, mantenido por el contacto entre cerdos domésticos criados en libertad, cerdos salvajes y posiblemente garrapatas autóctonas del género Ornithodoros, que son los más probables reservorios del virus. En 2014 se llevó a cabo un estudio en toda la República de Georgia para determinar la prevalencia del virus en las piaras de cerdos domésticos. De las 1.231 muestras obtenidas al efecto, todas resultaron negativas para el virus de la peste porcina africana. La probabilidad de no encontrar ningún animal positivo en una muestra de ese tamaño (n = 1.231) de una población con una prevalencia de la enfermedad estimada en un 1% resulta extremadamente baja (<0,0001). Por lo tanto es posible, pero muy poco probable, que el virus de la peste porcina africana estuviera presente en cerdos domésticos durante el periodo cubierto por el estudio. Estos datos parecen indicar que, en 2014, las piaras de cerdos domésticos no eran la fuente del virus, y que tal vez el ciclo endémico de la peste porcina africana repose en la circulación del virus en cerdos asilvestrados y salvajes y, posiblemente, en garrapatas autóctonas del género Ornithodoros.

ASSESSMENT OF THE LEVEL OF KNOWLEDGE OF MEDICAL PERSONNEL IN DIARRHEA AND HEMOLYTIC-UREMIC SYNDROME.

Survey have been conducted among medical professionals to test knowledge level of HUS and diarrheal diseases and to identify predictor variables for better knowledge. Cross-sectional survey have been conducted among medical personnel at different clinics in Tbilisi and in regions of Georgia. Participants were selected from different clinics in Tbilisi and in three biggest regional cities (Zugdidi, Batumi and Kutaisi) of Georgia. A total of 12 clinics were selected from them 6 were in Tbilisi and 2 at each regional cities. Clinics were selected based on their ability to provide services for gastrointestinal diseases, infectious diseases and kidney diseases. Data were entered into electronic database and analyzed using R v3.3.2. Descriptive statistics and methods of multivariate analysis were used for data analysis. 366 medical personnel have been interviewed. 73% (267) were females and 27% (99) males. Mean age was 40.8, IQR (27-52). A total of 64% (235) participants were from clinics located in Tbilisi. In multivariate analysis background in infectious diseases, female sex and having more than 10 years of medical experience were significantly associated with the total knowledge score of diarrheal diseases (p<0.05). High total knowledge score of HUS was detected among pediatricians (p<0.05). Trainings has been recommended for medical specialists to increase knowledge of diarrheal diseases and HUS to be able to identify those condition and to provide timely medical support for patients.

[Irradiation doses of population in mountainous Adjara region of Georgia].

Radionuclide content of food and water in high mountainous regions of Georgia - Adjara (Keda, Shuakhevi, Khulo) has been studied, internal and total irradiation doses for the population have been defined and preventive measures for its reduction have been proposed. Internal irradiation dose for the population caused by K-40 was identified as 0,63 mSv/y, total irradiation dose - 1,73 mSv/y, that slightly exceeds acceptable levels, due to this it seems desirable to provide some measures with aim to reduce the radiation dose of the population and conduct further observation of the radiation situation. Measures intended to reduce irradiation doses includes: provision of population with less radioactive water sources, the regulation of medical radiation procedures (mostly - X-ray diagnostic procedures), the rational use of fertilizers with 40K content, construction of buildings on the territories with the lowest values of gamma radiation and radon release from soil, use of materials with low content of natural radionuclides for building construction, provision of premises with effective ventilation and radiation monitoring of buildings at any stages of construction, reconstruction or repair.

[Radioecological situation of Racha-Lechkhumi region of Georgia and hygienic assessment of external irradiation doses of population].

Radioecological situation in Racha-Lechkhumi region of Georgia (Ambrolauri, Oni, Lentekhi, Tsageri districts) and annual effective doses of external irradiation of population have been studied. It was found that outdoor radiation background in Racha-Lechkhumi region is 58.0-169.0 nGy/h; average index is 108.9 nGy/h. Indoor radiation background is 68.0-192.0 nGy/h; average index is 137.4 nGy/h. The average annual effective dose of external irradiation of population in Racha-Lechkhumi region is 0.81 mSv/y, which exceeds the dose of similar type registered in most of countries. The implementation of adequate preventive measures for its reduction is required.

Interaction between Core protein of classical swine fever virus with cellular IQGAP1 protein appears essential for virulence in swine.

Here we show that IQGAP1, a cellular protein that plays a pivotal role as a regulator of the cytoskeleton interacts with Classical Swine Fever Virus (CSFV) Core protein. Sequence analyses identified residues within CSFV Core protein (designated as areas I, II, III and IV) that maintain homology to regions within the matrix protein of Moloney Murine Leukemia Virus (MMLV) that mediate binding to IQGAP1 [EMBO J, 2006 25:2155]. Alanine-substitution within Core regions I, II, III and IV identified residues that specifically mediate the Core-IQGAP1 interaction. Recombinant CSFV viruses harboring alanine substitutions at residues (207)ATI(209) (I), (210)VVE(212) (II), (213)GVK(215) (III), or (232)GLYHN(236) (IV) have defective growth in primary swine macrophage cultures. In vivo, substitutions of residues in areas I and III yielded viruses that were completely attenuated in swine. These data shows that the interaction of Core with an integral component of cytoskeletal regulation plays a role in the CSFV cycle.

Identification of an NTPase motif in classical swine fever virus NS4B protein.

Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive-sense single-stranded RNA virus within the Pestivirus genus of the Flaviviridae family. Here, we have identified conserved sequence elements observed in nucleotide-binding motifs (NBM) that hydrolyze NTPs within the CSFV non-structural (NS) protein NS4B. Expressed NS4B protein hydrolyzes both ATP and GTP. Substitutions of critical residues within the identified NS4B NBM Walker A and B motifs significantly impair the ATPase and GTPase activities of expressed proteins. Similar mutations introduced into the genetic backbone of a full-length cDNA copy of CSFV strain Brescia rendered no infectious viruses or viruses with impaired replication capabilities, suggesting that this NTPase activity is critical for the CSFV cycle. Recovered mutant viruses retained a virulent phenotype, as parental strain Brescia, in infected swine. These results have important implications for developing novel antiviral strategies against CSFV infection.

[The radiation background and hygienic assessment of external irradiation doses of population in some mountainous regions of Georgia].

The radioecological situation of Mtskheta-Mtianeti region of Georgia has been studied. Doses from external irradiation were determined and estimated. The average value of radiation background (RB) of open areas in Mtskheta-Mtianeti region accounts 84.6 nGy/h, which is nearly equal to the average values in the countries of western Europe. This shows that investigated territories have high natural radiation background, which considering the geographical position and geophysical situation of Georgia is normal. The average value of radiation background of buildings in investigated territories accounts 120.4 nGy/h, which is little more than worldwide average value. The average annual dose from external irradiation (without radon component) for population of Mtskheta-Mtianeti region accounts 0.99 mZv/y, which is slightly more than worldwide average value. Since approximately 2/3 of effective equivalent dose comes from internal radiation and 1/3--from external radiation, it's reasonable to suppose that the radiation load of population of Mtskheta-Mtianeti region is significant and requires implementation of radiation dose reduction measures.

[Comparison of radiation background and frequency of genetic abnormalities among infants of Adjara foreland].

Radioecological situation of Adjara foreland and external irradiation doses of population have been studied. A comparison of frequency of genetic abnormalities (congenital abnormalities, underweight) among infants born in 2004-2008 and magnitude of the radiation background (RB) of region was studied to establish the causal connection between genetic abnormalities and RB. It was found, that relatively high dose of external irradiation is not the determining negative factor affecting the health of the newborns. At the same time, various factors of low intensity in nature, the magnitude of the RB and total irradiation dose contribute to the development of a congenital anomaly.

Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine.

Here we have identified host cell proteins involved with the cellular SUMOylation pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating enzyme that interact with classical swine fever virus (CSFV) Core protein. Five highly conserved lysine residues (K179, K180, K220, K221, and K246) within the CSFV Core were identified as putative SUMOylation sites. Analysis of these interactions showed that K179A, K180A, and K221A substitutions disrupt Core-SUMO-1 binding, while K220A substitution precludes Core-UBC9 binding. In vivo, Core mutant viruses (K179A, K180A, K220A, K221A) and (K220A, K221A) harboring those substitutions were attenuated in swine. These data shows a clear correlation between the disruption of Core protein binding to SUMO-1 and UBC9 and CSFV attenuation. Overall, these data suggest that the interaction of Core with the cellular SUMOylation pathway plays a significant role in the CSFV growth cycle in vivo.

[Hygienic assessment of irradiation doses of Mtskheta-Mtianeti region' population].

Radionuclide content in the food and water in Mtskheta-Mtianeti region of Georgia has been studied, internal and total irradiation doses for the population have been defined and preventive measures for its reduction were detected. Internal irradiation dose for the population due to (40)K was identified as 1,58 mSv/y, total irradiation dose (external and internal irradiation) - 2,57 mSv/y, that is to some extent high than acceptable levels. To reduce the total irradiation dose of a population it is necessary to prohibit the use of high activity water for drinking; provision of the population with new sources of low activity water; minimize and control of irradiation doses from artificial sources including means of regulation of medical radiological procedures and rational use of fertilizers with (40)K content.

[Monitoring of the radioecological situation of Adjara seacoast].

One of the most important problems of the modern science is the study of biological, physiological and pathological influence of the radiation background on the surrounding environment. The disaster in the Chernobyl Atomic Power Station vitalized and sharpened the problem, as far as after the accident the Black Sea coast was exposed to the pollution. The Radiation background of Adjara seacoast has been studied in Georgia during the period of 1997 to 2002. The level of the radiation background in open areas lowered from 95 hgy/h to 93 hgy/h. The indicators of indoor radiation background have not been essentially changed--110 hgy/h. The average annual dose of irradiation of the population insignificantly lowered from 0,94 mZv/y to 0,937 mZv/y.

[Various indicators of the immune status of medical roentgenologists]. / Nekotorye pokazateli immunnogo statusa meditsinskikh rentgenologov.

Study of certain immune status indicators of medical roentgenologists has detected certain immunodeficiency associated with exposure to low doses of ionizing radiation. The number of T-lymphocytes has been noticed to be reduced, while the degree of reduction increases with age, duration of work in the sphere of radiation, and the value of the individual dose of radiation within a year. B-lymphocytes number is susceptible to changes in a smaller degree.

[Combined use of metronidazole and short-term hyperglycemia during radiation therapy of tumors in rats]. / Kombinirovannoe primenenie metronidazola i kratkovremennoi giperglikemii pri luchevoi terapii opukholei krys.

A simultaneous combined treatment with metronidazole and short-term hyperglycaemia, in contrast to application of each of these agents alone, enhanced considerably the therapeutic effect of radiation (a single and fractionated exposure). This was indicated by the increased rate of tumor regression, the number of animals with transient remission, and the number of cured animals which exhibited no relapse throughout the entire 90-day period of observation.

[Increase in the effectiveness of irradiating sarcoma-45 in rats using metronidazole]. / Povyshenie éffektivnosti oblucheniia sarkomy-45 krys metronidazolom.

A single exposure to ionizing radiation combined with the administration of metronidazole accelerated the regression of sarcoma-45 and increased the number of animals with fully regressed tumors as compared to control rats exposed to radiation alone. The maximum effect was registered when tumors were irradiated 90 min after the administration of metronidazole. With fractionated irradiation the radiosensitizing effect of metronidazole was less pronounced.