RADIOBIOLOGY
Introduction. One of the techniques used in retrospective biodosimetry according to the fluorescence in situ hybridization (FISH) method involves the estimation of stable chromosome aberrations (translocations) in human peripheral blood T-lymphocytes. In the case of uniform external and internal exposure, the interpretation of FISH data does not pose any problem, since the dose to T-lymphocytes that effects the translocation frequency can be simply interpreted as the dose to other organs and tissues. However, when the internal exposure is non-uniform and the doses to the organs differ by an order of magnitude, conversion from frequency of translocation to dose estimates becomes a complicated task.
Objective. To review the main parameters necessary for the retrospective assessment of doses using the FISH method in the case of internal uneven and prolonged β-irradiation.
Findings. The present analytical review considers problems associated with determining the following parameters: (1) Frequency of radiation-induced and background translocations; (2) Conversion factors from the frequency of radiation-induced translocations to the dose to T-lymphocytes (α); (3) Conversion factors from the dose to T-lymphocytes (cytogenetic dose) to the dose to critical organs and tissues (Borg ), which depend on age at the time of exposure. General approaches and estimates of (α) based on the construction of in vivo and in vitro calibration curves for external and internal exposure were analyzed. The dose-accumulation features in different T-cell populations from prolonged internal non-uniform exposure (using 90Sr as an example) were considered in terms of the applicability of the model approach to assessing accumulated doses. Uncertainties of dose estimates in retrospective biodosimetry are discussed and further research directions proposed.
Conclusions. In the case of non-uniform internal exposure with a low dose rate, converting translocation frequency to dose estimates becomes a complex task. The α and Borg conversion coefficients, which are derived from independent data sets, can be based on various approaches, including modelling. Currently, approaches to assessing their uncertainties, as well as the uncertainties of the dose obtained using the FISH method, remain undeveloped. Therefore, these coefficients require further studies.
Introduction. The influence of adverse factors including ionizing radiation leads to a violation of key transcription factors expression and the ratio of the main types of T-helper cells, which in turn initiates a wide range of immunopathological disorders.
Objective. The objective of this research was to study the mRNA expression of the SPI1 and GATA3 genes, as well as the composition of T-helper type 1 and 2 subpopulations, in chronically exposed people during the period of radiation exposure late effects development.
Mаterials and methods. The study was carried out on peripheral blood mononuclear cells obtained from 98 residents of the Techa riverside settlements. Two study groups were formed: the group of exposed individuals (average accumulated dose for the red bone marrow radiation was 706.8±62.7 mGy) and the comparison group (radiation dose did not exceed 70 mGy). The median age of the studied individuals at examination was 71.1 ± 0.9 years (58–87 years). The relative mRNA content of the studied genes was assessed using real-time PCR. The number of T-helpers of types 1 and 2 in the populations of T-helpers of central and effector memory was calculated using the flow cytometry method.
Results. There was a decrease in the absolute and relative number of type 2 T-helpers included in the T-helpers of central memory in chronically exposed individuals. In people with accumulated doses ≥1000 mGy, an increase in the Th1/Th2 ratio of T-helpers of the central memory (p=0.01), as well as the positive correlation relationship between the relative content of type 2 T-helpers of the effector memory and the expression of the GATA3 gene were registered relative to unexposed individuals.
Conclusions. The obtained results indicate that changes in the composition of T-helper cell subpopulations in chronically exposed individuals are not pronounced in the long-term period. However, these changes may directly depend on the total absorbed dose, which in turn determines the prospects for further analysis of the health status of people exposed to chronic high-dose radiation.
Introduction. An increased risk of malignancy and cardiovascular diseases is revealed in exposed individuals from different cohorts. Monocyte and natural killer (NK) cells modulate inflammation and carcinogenesis.
Objective. To evaluate absolute and relative cell counts in monocyte and natural killer cell subpopulations in the peripheral blood of individuals exposed to chronic irradiation.
Materials and methods. Thirty-five persons from the Techa River cohort were examined, divided into three subgroups depending on the radiation absorbed dose calculated to the red bone marrow (RBM) (70–249 mGy; 250–699 mGy; 700–1429 mGy, respectively). The mean age of patients was 74.9 years; the mean value of the radiation absorbed dose to RBM was 542.0±65.3 mGy, while that of the radiation absorbed dose to thymus and peripheral lymphoid organs was 99.7±14.4 mGy. The comparison group consisted of 10 persons without a history of anthropogenic irradiation of similar gender and ethnicity, mean age — 71.8 years.
Results. In the second dose subgroup, the proportion of CD14–CD16+ monocytes was statistically significantly higher (8.47%) than in the comparison group (5.52%, p=0.014), and the absolute CD14–CD16+ monocytes count (0.040×109/l) was also higher than in the third subgroup (0.018×109/l, p=0.044) without correlations with radiation and non-radiation factors. No statistically significant differences of other studied parameters between the groups were revealed.
Conclusion. In persons from the second subgroup the relative number of CD14–CD16+ monocytes was statistically significantly higher than in the comparison group; the absolute CD14–CD16+ monocytes count was also higher than in the third subgroup without correlations with factors of a radiation and non-radiation nature. The findings are preliminary.
Introduction. Exposure of the brain to high doses of ionizing radiation is an established risk factor for the development of neoplasms and associated cognitive disorders. However, the impact of long-term low-dose irradiation on the brain and higher nervous system, including the development of anxiety-depressive disorders, remains an unsolved problem.
Objective. To study the effect of fractionated gamma-irradiation in doses of 0.1 Gy, 1 Gy and 5 Gy in the early postnatal period on indices of depression-like states in C57Bl/6 mice at the age of 1 and 6 months.
Materials and methods. The animals were irradiated during the first month of life. Cumulative doses (0.1 Gy, 1 Gy and 5 Gy) were obtained in the mode of fractionated irradiation (20 fractions). 2 control groups were formed comprising intact animals and falsely irradiated animals. The presence of a depression-like state was evaluated in the “tail holding” test at the age of 1 month and 6 months.
Results. Age-related changes were manifested by a decrease in depression-like behavior in 6-month-old mice compared with 1-month-old mice. Stress induced by performing radiation-related manipulations, which had no significant effect on 1-month-old mice, led to the development of marked depression-like states in the same animals at 6 months of age. Radiation exposure led to the development of a dose-dependent antidepressant-like effect, which was more pronounced in animals at the age of 6 months after fractionated irradiation at doses of 0.1 Gy and higher.
Conclusions. Fractionated gamma-irradiation does not lead to the development of depression-like symptomatology in mice in the early postnatal period, but, on the contrary, is characterized by antidepressant action.
VIROLOGY
Introduction. Over the past two years, there has been an increase in measles morbidity in Russia and other countries. In order to assess the heterogeneity of clinically significant strains of Measles morbillivirus to reveal the sources of infection and transmission routes strains, a molecular genetic study thus becomes an urgent task. In this paper, a genetic identification of clinical strains of measles virus detected in 2023–2024 is compared with global variants as well as Russian strains detected in previous years.
Materials and methods. Forty measles virus genome sequences isolated from nasopharyngeal swab samples obtained in Moscow and Novosibirsk in 2023–2024 were included in the study. The data were then compared with strains collected in Russia in May 2023 and deposited at the Central Research Institute of Epidemiology, as well as strains collected in 2020 and 2021 in Moscow.
Results. The nucleotide sequences of studied Measles morbillivirus strains were categorized into different phylogenetic groups within genotype D8. For samples of genotype B3 collected in 2020 and 2023, a comparative analysis was performed to identify the region of origin. Phylogenetic analysis of Russian and foreign variants of measles virus suggests that strains currently circulating in Russia may be a variety of strains that had previously circulated in other countries and independently spread to Russia in 2023. After analyzing the most frequent nucleotide substitutions in various measles virus genes, the most variable genes were identified to provide a basis for the extension of phylogenetic analysis.
Conclusions. The proposed approach to molecular genetic testing of complete and partial genome sequences of clinical isolate of measles virus detected in 2023–2024 in Moscow and Novosibirsk made it possible to identify strain subgroups that differ in origin. The comparison of the Measles morbillivirus strains sequenced in the present research with global sequences allowed us to detect similar sequences identified both in 2023 and in previous years in various countries of the world. The analysis of epidemiologically significant strains of Measles morbillivirus shows that N gene can be used to reliably determine the main genotype; however, this approach is not sufficient for studying the transmission pathways of the virus.
SPACE MEDICINE
Introduction. Considering the risks of cardiovascular events during all phases of spaceflight (SF), it is relevant to evaluate the levels of cardiac markers sST2 and NT-proBNP in ground-based simulations of exposure to adverse SF factors.
Objective. To identify the levels of sST2 and NT-proBNP as risk criteria for the development of cardiovascular changes following end-to-end simulation of SF stages on the CF-18 centrifuge.
Materials and methods. The levels of cardiac markers sST2 and NT-proBNP were assessed during exposure to chest-to-back overloads of up to 4.5 units and simulated vestibular sensory conflict on a CF-18 centrifuge for 60 min in six healthy male subjects. The sST2 levels were assessed by solid-phase enzymelinked immunosorbent assay (ELISA). NT-proBNP concentration was measured by immunofluorescence method on a Finecare TM FIA FS-113 analyzer (from Guangzhou Wondfo Biotech).
Results. During the end-to-end simulation of SF stages, the response of the subjects’ cardiovascular system was adequate to the loads imposed. The levels of the cardiac markers sST2 and NT-proBNP in venous blood of the subjects did not significantly increase after spinning on the centrifuge.
Conclusions. In the present study, no significant changes indicative of biochemical signs of pathologic overstretching or myocardial damage were observed during rotation on the CF-18. Assessment of individual sST2 levels prior to exposure and in dynamics can be used to probabilistically predict individual sensitivity and adaptation reserves of the heart to unfavorable CP factors.
Introduction. Due to the fact that manned space flights beyond Earth orbit are planned in the near future, it becomes relevant to study the effects of the Earth’s reduced magnetic field on humans.
Objective. To evaluate the features of sensorimotor reactions, quality of night sleep (nocturnal sleep) and the development of daytime sleepiness during a 24-hour stay under hypomagnetic conditions (HMC).
Materials and methods. Experimental studies with the participation of 6 male volunteers aged 26 to 37 years were conducted in 2023. In total, four experimental series were carried out, lasting 24 hours each. The subjects were exposed to hypomagnetic conditions in three groups (the average value was between 0.05–0.14 µT). There was no exposure to such conditions in the placebo group.
The research methods included questionnaires regarding the quality and characteristics of night sleep, daytime wakefulness, as well as the study of sensorimotor functions. Statistical processing was carried out by the Statistica 13.0 software package.
Results. Daytime sleepiness was found to increase under hypomagnetic conditions in 66% of observations as compared to 33% of cases in the placebo series (p=0.003). Immediately following the cessation of experimental exposure, a rapid activation of the central nervous system was observed, which was expressed in a statistically significant decrease in the total visual-motor reaction time.
Conclusions. Under hypomagnetic conditions, the work of brain sleep mechanisms is preserved. Daytime drowsiness that develops under hypomagnetic conditions indicates the possibility of changes in circadian rhythmicity in brain activating systems. The rapid activation of the central nervous system reported immediately following the termination of hypomagnetic conditions has a compensatory character. The revealed features of hypomagnetic conditions influence on the sleep-wake cycle and sensorimotor functions suggest further studies of daytime sleepiness using additional subjective and objective methods of wakefulness level and activity of the central nervous system assessment.
MARINE MEDICINE
Introduction. During their descent under water, divers may suffer from acute toothache attacks (barodentalgia), creating an emergency that leads to the termination of diving descent. Barodentalgia can be caused by hypoxic process in the pulp of filled teeth under increased intrapulpal pressure.
Objective. To reveal the peculiarities of hypoxic processes in the pulp of filled teeth under hyperbaric exposure basing on oximetry and fluorescence change parameters.
Мaterials and methods. The study involved 34 male divers who underwent a dental examination at the first stage to select individuals for the second stage of the experiment. 24 subjects were selected for the second stage and evaluated for oximetric (mixed blood saturation) and fluorescent (reduced coenzyme NADH, oxidized coenzyme FAD, fluorescent oxygen consumption index — FOCI) indices of filled teeth. The evaluation was performed by optical tissue oximetry (OTO) and laser-induced fluorescence (LIF) methods before and after immersion in a barocamera at pressure of 0.4 MPa while breathing air.
Results. Following exposure to increased pressure of the gas medium as compared to the initial values in the filled teeth, the following phenomena were observed: decrease in pulp saturation by 33.7% (p<0.05); increase in NADH by 14.4%; decrease in FAD by 22.9%; increase in FOD by 73.4% (p<0.05).
Conclusions. The revealed changes in the indicators of mixed blood saturation, NADH, FAD and FOCI confirm the presence of hypoxic process in the pulp of filled teeth under hyperbaric exposure.
SPORTS MEDICINE
Introduction. Modern scientific studies demonstrate the effectiveness of hyperbaric oxygenation in assisting recovery following physical exertion including those affected by COVID-19 infection.
Objective. The study sets out to identify the beneficial effects of hyperbaric oxygenation therapy in assisting the recovery of athletes under medium-altitude conditions, including those who have previously undergone COVID-19, by examining respiratory and circulatory systems.
Materials and methods. The study was performed on 39 highly qualified athletes during a period of training in mountainous areas. The athletes’ heart rate variability, central hemodynamics, saturation and external respiration were determined prior to hyperbaric oxygenation, as well as immediately following the procedure, 10 min after the procedure, and following a course of 7 procedures.
Results. According to heart rate variability indices in women who underwent COVID-19, there was a tendency to decrease heart rate 10 min after hyperbaric oxygenation and very a slow wave power index after the course of (before — 665.65 (592.54; 921.07) ms2; after — 541.47 (371.01; 840.89) ms2, p < 0.05). After the first session there was a decrease in systolic blood pressure (before — 117 (111; 120) mm Hg; after — 109 (104; 115) mm Hg, p < 0.03), as well as in the index of volumetric airflow velocity at the moment of exhalation of 50% of forced vital capacity of lungs. A comparison of men’s parameters revealed a decrease in peripheral vascular resistance and blood pressure. In women and men who had previously suffered COVID-19 infection, the index of impaired oxygen uptake from the microcirculation system decreased under the influence of hyperbaric oxygenation.
Conclusions. Hyperbaric oxygenation therapy is a safe and effective method for assisting the recovery of athletes under medium-altitude conditions, including those who have previously suffered COVID-19 infection. The observed improvements in functional state are manifested over the course of application (7 sessions).
TOXICOLOGY
Introduction. The widespread use of pesticides, which ensures the sustainable development of agriculture and global economic growth, necessitates the constant monitoring of their harmful effects on human health and the environment.
Objective. To analyze and systemically review scientific publications on the prevalence of acute pesticide poisoning and trends in their use in order to identify the causes and structure of acute pesticide poisoning at the present time.
Materials and methods. A search of the scientific literature is carried out in electronic bibliographic databases in the Russian (eLibrary, CyberLeninka) and English (Web of Science, Scopus, PubMed, Google Scholar, Cochrane Library) languages.
Results. The risks of pesticide poisoning remain high in many countries of the world among both adults and children. In the structure of acute pesticide poisoning, household and suicidal poisoning with organophosphate and halogenated insecticides, anticoagulant rodenticides and pyrethroids are prevalent. Poisonings that occur at mass-, group- and family levels often have fatal outcomes, whether among agricultural workers or urban residents. The problem of acute poisoning with extremely dangerous limited-use substances based on aluminum or zinc phosphide is relevant not only in industrial agriculture, but also under domestic conditions and when working in personal subsidiary farms.
Conclusions. Strengthening controls and ensuring strict compliance with sanitary and hygienic standards of individual and public safety in the storage, use and disposal of pesticides, as well as combating their illegal trafficking, will minimize the risks of acute poisoning involving pesticides under industrial and domestic conditions.
CLINICAL MEDICINE
Introduction. Herpesvirus infections — in particular, those caused by human betaherpesvirus 6A/B (HHV-6A/C), are a serious problem at the present time due to their ubiquity, polymorphism of manifestations, lifelong persistence in the body with the possibility of reactivation, and need for comprehensive diagnostics to the form of infection. Herpesvirus infections are especially serious when occurring in children with recurrent respiratory diseases.
Objective. To propose a modern method of differential diagnosis (DD) of active and latent forms of HHV-6A/B infection in children to optimize patient management tactics.
Materials and methods. To build a discriminant model, 152 patients aged 1 month to 17 years inclusive were included in the study, 112 of them making up a training sample, while 40 comprised a test sample. A dichotomous variable was taken as a response variable: 1 — latent form of HHV-6A/B infection (n = 89), 2 — active (n = 23). 27 potential predictors were considered. The test sample consisted of 40 children. Statistical processing was performed using Microsoft Excel and StatSoft Statistica 7.0
Results. The developed prognostic model of DD of active and latent forms of HHV-6A/B infection in children, which takes into account the severity of fever, the presence of cough, the absolute neutrophil count and the value of threshold cycles of HHV-6A/B DNA, is characterized by its high sensitivity (91.3%) and specificity (94.4%). The presented example reflects the step-by-step use of the model.
Conclusions. The prognostic model can be used in practice for identifying DD forms of HHV-6A/B infection in the presence of lymphoproliferative and respiratory syndromes in children, for the detection of HHV-6A/B DNA in the blood, and to substantiate indications for immunotropic therapy.
Introduction. The treatment of malignant neoplasms of the oral mucosa implies a combined treatment, whose first stage generally involves surgery. However, the most common non-personalized surgical methods are based on resection of the tongue, often affecting more than half of the organ, which can lead to significant functional deficiency and disability of patients.
Objective. To demonstrate the possibility of tongue defect reconstruction using preoperative computer 3D planning through clinical cases.
Маterials and methods. From 2021 to 2024, four patients with primary cancer of the lateral surface of the tongue were operated on using this methodology at the Maxillofacial Surgery Department of the NMICO FMBA of Russia. All patients underwent hemiglossectomy and preventive cervical lymphadenectomy on the affected side, with simultaneous reconstruction of the tongue using a radial forearm flap. The average age of the patients was 53 years; males outnumbered females by a ratio of 3:1. Patients presented with stages rT1-rT4; histological examination revealed no regional lymph node involvement (N0) in any patient. Preoperative instrumental examinations included: magnetic resonance imaging (MRI) of the soft tissues of the maxillofacial area with contrast enhancement; multislice computed tomography (MSCT) of the maxillofacial area with contrast enhancement; MSCT of the donor area (forearm) with contrast enhancement; Doppler ultrasound of the brachiocephalic trunk vessels and donor area vessels; transnasal endoscopic laryngoscopy with swallowing tests (three-swallow test) with video recording. All patients were surveyed preoperatively and postoperatively using EORT QLQ — H&N35, EORT QLQ — C30, FACT– H&N, MD Anderson, and VHI-10 questionnaires. Patients with abundant hair in the donor area underwent laser hair removal prior to hospitalization. After performing computer simulation of the surgical intervention using Slicer and Blender software, templates were printed on a Elegoo Saturn 2 printer. Assessment of speech and swallowing functions was carried out by a speech therapist specializing in these areas using the Pokrovsky protocol and Vospector-DSI software at both preoperative and postoperative stages. The attending physician performed anthropophotometry and video recording of patient complaints and speech at all stages of care. The postoperative period was without complications; nasogastric tubes were removed on the 12th day; the average hospital stay was 14 days.
Results. The flap survival rate was 100% across the entire series of observations. Oncological radicality was achieved at R0 for all patients. The average duration of the surgical intervention was 288 minutes. In three patients, the acoustic parameters of speech were within normal limits (in one patient, this parameter could not be assessed due to systemic speech underdevelopment caused by hearing impairment). The average syllable intelligibility coefficient according to Pokrovsky was 88%. All patients adapted to their usual diet and continued their professional activities. According to the results of the EORT QLQ — H&N35, EORT QLQ — C30, and FACT — H&N questionnaires, patients rated their quality of life as good in one case and excellent in three cases.
Conclusions. The developed algorithm for preoperative computer planning is promising. The use of surgical templates allowed for adequate oncological radicality, synchronized the simultaneous work of two surgical teams, reduced the duration of anesthetic assistance (with an average surgical intervention time of 288 minutes), and achieved good functional and aesthetic results. However, this methodology requires further refinement in a larger group of patients.
Introduction. Central venous catheter (CVC) provides intensive infusion and transfusion therapy in cancer patients, but catheter placement and operation are often associated with complications.
Objective. To determine the incidence of complications associated with CVC in patients with blood disorders.
Materials and methods. The study involved 3115 patients and 46 bone marrow donors. The right subclavian vein was catheterized in 2600 (82.2%) patients, the left subclavian vein in 552 patients (17.5%), and the internal jugular vein in 9 patients (0.3%). All persons underwent radiologic control; bacteriological blood examination was performed in case of suspected infection.
Results. Early revealed complications were: hematoma in 4.0% of patients; bleeding — in 2.3%; subclavian artery puncture — in 2.7%; pain and paresthesia of the upper limb — in 1.7%; lymphorrhea — in 1.4%; weakness / collapse — in 1.2%; extravasation — in 1.1%; catheter thrombosis — in 1.1%; less frequently, pneumothorax was detected in 0.2% of patients; allergic reaction to anesthetic — in 0.1%. Delayed complications (infiltrate, phlebitis, thrombophlebitis) were diagnosed in 2.7% of patients, bacteremia — in 2.4%, delayed bleeding — 0.4%. Among infections, Gram positive microorganisms were more frequently detected in 61.8% of cases, Gram negative in 29.7% (p < 0.01), and rarely fungal pathogens in 8.5% (p < 0.001). It was not possible to catheterize the central vein due to anatomical features of the patient in 0.5% of cases.
Conclusions. The analysis of trunk vein catheterization in patients with blood disorders established a high rate of hematomas, bleeding, subclavian artery punctures; among delayed complications, infiltrate, phlebitis, and bacteremia. Infectious complications demonstrated a prevalence of Gram-positive infectious agents.
CLINICAL PHARMACOLOGY
Introduction. A comprehensive approach to treatment of chronic prostatitis, representing a widespread and poorly treatable disease, includes the use of antibacterial, anti-inflammatory medicines, etc. In this context, a promising approach to the treatment of chronic prostatitis involves the use of bioregulatory peptides isolated from bovine prostate tissue.
Objective. To study the effect of cattle prostate extract containing bioregulatory peptides on the functional activity of lymphatic vessels.
Маterials and methods. The study was performed on isolated lymphatic vessels of rats. The range of studied concentrations of the substance was 2–10 µg/ mL (in terms of water-soluble peptides).
Results. Bioregulatory peptides included into the prostate extract impacts the vasomotor activity of lymphatic vessels. In the range of studied concentrations (2–10 µg/ml), the substance has a stimulating effect on lymphangion motility. This is realized by increasing the rate of lymphatic vessel contractions, which effect is most pronounced at the concentration of 5 µg/ml as a 37.6% (p ≤ 0.05) of base level. The obtained stimulating effect is stable during 30-min “washing” of lymphatic vessels with physiological solution.
Conclusions. Water-soluble bioregulatory peptides contained in the extract of cattle prostate and having organotropic action on the prostate gland may contribute to the reduction of tissue edema by activating the motility of pelvic lymphatic vessels.
EPIDEMIOLOGY, MOLECULAR EPIDEMIOLOGY
Introduction. The impact of the epidemic circulation of the novel coronavirus respiratory infection on the Russian population in terms of morbidity, mortality and lethality from respiratory diseases (RD) and consequent social damage requires an in-depth study.
Objective. The study set out to compare the morbidity, mortality and lethality dynamics of the total population of the Russian Federation due to respiratory diseases (RD) in 2016–2021 and COVID-19 in 2020–2021.
Materials and methods. The study was based on official statistical information provided by the Ministry of Health of the Russian Federation, Russian Federal State Statistics Service and Russian Federal Service for the Oversight of Consumer Protection and Welfare on the morbidity and mortality of the population due to RD (codes J00-J98 in accordance with the International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10). The data for 2020–2021 are compared with the average morbidity and mortality rates of the Russian population for 2016–2019. Statistical data processing was carried out using Statistica software, version 10, and Epi5 (WHO), version 7. When comparing the indicators, the relative risk, 95% confidence interval, and Matel-Hansel2 were calculated. The differences were considered to be significant at p < 0.05.
Results. The primary and general morbidity and mortality from RD in the Russian population in 2020–2021 exceeded the average levels of similar indicators for 2016–2019. The increase in indicators was associated with a larger number of patients presenting with pneumonia, as well as interstitial and suppurative lung diseases. This was accompanied by an increase in hospital mortality and lethality due to RD and COVID-19 in 2020–2021.
Conclusions. The epidemic circulation of the new coronavirus infection was accompanied by a significant increase in the morbidity and mortality of the population from RD.
ISSN 2713-2765 (Online)