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Å. Laestadius, A. Nilsson, R. Bennet, G. Bogdanovic, M. Eriksson

The national Swedish immunisation programme includes vaccine against diphtheria, tetanus, polio, pertussis, Haemophilus influenzae type B, Pneumococcus as well as measles, mumps and rubella. Data were collected on hospital admissions for children 0- 17 years of age of vaccine-preventable diseases during 2008-2013 at Astrid Lindgren Children's Hospital, Stockholm. Patients were identified by discharge diagnosis codes as well as from the clinical microbiology laboratory. There were rare cases of measles and mumps, and only a few cases of invasive bacterial diseases. The dominating pathogens were influenza A and B, rotavirus and varicella zoster virus. Our national programme is effective, but vaccine preventable infections still cause significant morbidity in young children. An extended vaccine programme might significantly reduce the need of hospitalisations.

Å. Fowler, Sofia Ygberg, G. Bogdanovic, R. Wickström

Background: Tick-borne encephalitis (TBE) is a major cause of meningoencephalitis in children in endemic areas, and long-term residual problems are not uncommon. Currently, no predictive markers in the acute phase are available that identify children at risk of incomplete recovery. We measured cytokines, chemokines and markers of neuronal damage in cerebrospinal fluid (CSF) in children with TBE and central nervous system (CNS) involvement. Methods: CSF from 37 children with TBE with CNS involvement was analyzed. Concentrations of 16 cytokines, chemokines and 5 markers of neuronal damage were assessed in CSF, using a multiplex assay, and correlated with clinical findings in the acute phase (n = 37), and with long-term outcome (n=22). Results: Significantly higher levels of CSF interferon (IFN)-&ggr;, interleukin (IL)-4, IL-6 and IL-8 were detected in the acute phase from children who later developed sequelae. Although most of the studied markers of neuronal damage displayed no significant differences between children with sequelae and those with good outcome, neuron-specific enolase correlated inversely. The grade of CSF pleocytosis correlated positively with the levels of IFN-&ggr;, IL-4 and IL-6; however, pleocytosis alone did not predict sequelae. Increasing age correlated positively with IL-4, IL-6 and IL-8 values. Conclusions: The mechanism underlying the CNS pathology causing sequelae in TBE appears related to the grade of inflammation in CNS, rather than to direct neuronal destruction. High concentration of IFN-&ggr;, IL-4, IL-6 and IL-8 in CSF might indicate a risk for incomplete recovery in childhood TBE.

L. Stojanovich, G. Bogdanovic, A. Djokovic

Background Because of the fact that systemic lupus erythematosus (SLE) causes joint and muscle pain, fatigue, depression, the very thought of exercising can be a challenge for patients. Although exercise can be beneficial and can significantly improve the quality of life. Objectives The aim of the study is to determine the form of physical activity in SLE patients that could improve their quality of life. Although exercise can be beneficial and can significantly improve the quality of life. Methods This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women did exercise for 30 minutes, 3 times per week during the same period. FSS (fatigue Severity Scale), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. Results Fatigue was present in all patients (FSS score 53.8 ± 5.7; min 39, max 63) before starting the exercise. Fatigue was present in 11 patients (18.3%) after the physical activity while 49 (81.7%) patients did not experience it (FSS score 29.1 ± 7.8; min 18, max 45). Before starting the exercise the largest number of patients, 40 (66.67%) of them, was in a moderate depressed state, while after physical activities the greatest number of patients, 37 (61.66%), had a mild mood disturbance. There are high statistical differences (p<0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. Comparing the different types of physical activities there were not any statistically significant differences (p>0.05) in values of FSS and BDI questionnaire. A statistically significant difference was observed in terms of reducing the parameters of pain, general health and mental health in a group that had a physical activity on a bicycle ergometer evaluated by the SF36 questionnaire (p<0.05). Conclusions Our study has shown that a continuous physical activity in SLE patients significantly improves their quality of life by reducing fatigue and depressive reactions without negative impacts on the activity of their disease. The type of physical activity was not relevant. References Ayan C, Martin V. Systemic lupus erythematosus and exercise.Lupus 2007; 16:5–9. Mancuso CA,Perna M, Sargent AB, Salmon JE.Perceptions and measurements of physical activity in patients with systemic lupus erythematosus. Lupus 2011;20:231–42. Wolkmann ER, Grossman JM, Sahakian LJ, Skaggs BJ, FitzGerald J, Ragavendra N, et al. Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus.Arthritis Care Res 2010;62:258–65. Acknowledgement This work was supported by research grant number 175041 for 2011 - 2016, issued by the Ministry of Science of the Republic of Serbia, and by research grant number TR 32040 for 2011 - 2016, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None declared

Danica Jović, Mariana Seke, A. Djordjevic, Jasminka Mrđanović, L. Aleksić, G. Bogdanovic, A. Pavić, J. Plavec

Doxorubicin is a very potent chemotherapeutic drug, however its side effects limit its clinical use. The aim of this research was to investigate the properties of a fullerenol/doxorubicin nanocomposite, its potentially cytotoxic and genotoxic effects on malignant cell lines, as well as its toxicity towards zebra fish embryos. Chromatographic, NMR and mass spectral analysis of the nanocomposite imply that interactions between doxorubicin and fullerenol are non-covalent bonds. The stability of the nanocomposite was confirmed by the use of atomic force microscopy, dynamic light scattering and transmission electron microscopy. The nanocomposite, compared to the free doxorubicin at equivalent concentrations, significantly decreased the viability of MCF-7 and MDA-MB-231 cells. The flow cytometry results indicated that doxorubicin-loaded fullerenol could remarkably increase the uptake of doxorubicin suggesting that fullerenol might be a promising intracellular targeting carrier for the efficient delivery of antitumor drugs into tumor cells. The nanocomposite also affected cell cycle distribution. A genotoxicity test showed that the nanocomposite at all examined concentrations on MCF-7 and at lower concentrations on MDA-MB-231 cells caused DNA damage. Consequently, cell proliferation was notably reduced when compared with controls. Results of the zebrafish embryotoxicity assay showed a decreased overall toxicity, particularly cardiotoxicity and increased safety of the nanocomposite in comparison to doxorubicin alone, as manifested by a higher survival of embryos and less pericardial edema.

G. Bogdanovic, A. Djordjevic

Since their discovery, fullerenes, carbon nanotubes, and graphene attract significant attention of researches in various scientific fields including biomedicine. Nano-scale size and a possibility for diverse surface modifications allow carbon nanoallotropes to become an indispensable nanostructured material in nanotechnologies, including nanomedicine. Manipulation of surface chemistry has created diverse populations of water-soluble derivatives of fullerenes, which exhibit different behaviors. Both non-derivatized and derivatized fullerenes show various biological activities. Cellular processes that underline their toxicity are oxidative, genotoxic, and cytotoxic responses.The antioxidant/cytoprotective properties of fullerenes and derivatives have been considered in the prevention of organ oxidative damage and treatment. The same unique physiochemical properties of nanomaterials may also be associated with potential health hazards. Non-biodegradability and toxicity of carbon nanoparticles still remain a great concern in the area of biomedical application. In this review, we report on basic physical and chemical properties of carbon nano-clusters--fullerenes, nanotubes, and grapheme--their specificities, activities, and potential application in biological systems. Special emphasis is given to our most important results obtained in vitro and in vivo using polyhydroxylated fullerene derivative C₆₀(OH)₂₄.

H. Gaines, J. Albert, M. Axelsson, T. Berglund, M. Gisslén, A. Sönnerborg, A. Blaxhult, G. Bogdanovic et al.

Abstract In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.

G. Bogdanovic, S. Trajkovic

Noise is any unwanted sound. This means that every sound effects (buzzing, noise, magnifier, speech and so on.), which interferes with work or rest, is noise. Communal noise generated by all noise sources that are found in the human environment, excluding the noise that occurs at the workplace in the industrial plants. It mainly comes from traffic and it's called traffic noise. Department of Public Health Vranje is authorized and accredited professional organization that performs measurements of noise pollution in the city of Vranje. Measurement of noise in both cycles included ten measuring points that are found in a residential area. The level of acoustical load at each measurement point is followed by three measurements in the daily interval and two measurements in a night interval. Made the daytime, evening and nighttime measurements at 53 measuring points (a total of 159 measurements) over a period of 15 minutes of noise. From the 53 measuring points are higher noise level at measuring point 51 (almost all measuring points) and ranges from 2 to 47.2 dB (tab. 1 Measuring points of noise pollution Vranje-2015-day / evening / night ). The way to combat environmental noise largely depends on the degree of development, economy, culture and politics. There is no estimate on the world level about the impact of noise on the environment and human health as well as estimates of the price of that impact. The existence of a modern harmonized with European regulations normative acts will be aimed at the maximum limit and control the exposure of the population of acoustic pollution.

G. Bogdanovic, S. Trajkovic, Tijana Mićić

Lichen is a symbiotic plant built by the cells of algae and fungi hyphae. Algae are usually presented - green (Chlorophyta) or blue green (Cyanophyta), a mushroom commonly found is ascomycetae and sometimes basidiomycetae. Mushrooms receive oxygen and carbohydrates from algae, and they in turn provide water, CO2 and mineral salts. Lichens are often found on trees and rocks in unpolluted environments and can be used as a bioindicator species. In during 2015-2016. was realized a survey of epiphytic lichen flora of the western mountains in environment of Vranje. Sampling was carried out at 4 locations: Borino brdo, Krstilovica, Markovo Kale and Pljackovica. Based on the collected and determined samples can be concluded that the study implemented of the area of 25 species of lichens of which: 8 as crust, leafy 12 and 5 shrub. The research results indicate that the lichen flora of the western mountains environments Vranje of a rich and diverse as a result of favorable geographic position, geological and soil composition, climate and plant cover that provide opportunities for the development and survival of lichens.

D. Jakimov, V. Kojić, L. Aleksić, G. Bogdanovic, Jovana J. Ajduković, Evgenija A Djurendić, Katarina M. Penov Gaši, M. Sakač et al.

G. Bogdanovic, L. Stojanovich, A. Djokovic, N. Stanisavljevic

Given the crucial events in systemic lupus erythematosus (SLE) such as joint and muscle pain, fatigue, depression, obesity and osteoporosis, the very thought of exercising can be challenging. This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women performed isotonic exercises (to stretch and lengthen muscles and improve the range of motion) for 30 minutes, 3 times per week during the same period. Fatigue Severity Scale (FSS), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. At baseline FSS score was 53.8 ± 5.7 and after the physical activity FSS score was 29.1 ± 7.8 (FSS ≥ 36; fatigue is present). The largest number of patients (66.7%) was in a moderate depressed state at the baseline, while after physical activities 61.7% of patients, had a mild mood disturbance. There were significant differences (p < 0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. The type of physical activity had no influence in FSS and BDI values. Continuous physical activity, regardless of its type, significantly improved quality of life of SLE patients. We recommend regular physical activity as an integral part of modern therapeutic approach in this patient population.

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