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    Toxic Elements in Soil of Children's Playgrounds in the Belgrade Urban Area

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    Za zemljišta urbanih gradskih područja se očekuje da budu zagađena potencijalno toksičnim elementima (PTE), zbog saobraćaja, urbanizacije i industralizacij. Budući da deca provode dosta vremena na igralištima, igrajući se zemljom, njihova izloženost ovim elementima i potencijalni štetni efekti na zdravlje su poslednjih godina postala vrlo značajna tema. [1-2] Cilj ovog rada je bio određivanje sadržaja arsena (As), kadmijuma (Cd), olova (Pb), nikla (Ni), hroma (Cr), bakra (Cu) i cinka (Zn) u 17 uzoraka zemljišta sa različitih dečjih igrališta u urbanoj zoni Beograda. Uzorci su pripremani kiselom mikrotalasnom digestijom, a sadržaj elemenata je određivan metodom induktivno spregnute plazme optičke emisione spektroskopije (ISP-OES). Tačnost metode je procenjena upotrebom sertifikovanog referentnog materijala NIST 2711a, i dobijene su vrednosti u opsegu 80-120%. Prosečna koncentracija ispitivanih PTE sledi navedeni niz: Zn (68,24 mg/kg) > Ni (60,99 mg/kg) > Cr (51,685 mg/kg) > Pb (21,615 mg/kg) > Cu (19,785 mg/kg) > As (8,1125 mg/kg) > Cd (0,1566 mg/kg). Koncentracije svih ispitivanih PTE su u saglasnosti sa legislativma Republike Srbije, Evropske unije (EU) i Svetske zdravstvene organizacije (SZO). S obzirom na potencijal PTE za bioakumulaciju i uključivanje u lanac ishran, vrlo je važno njihovo konstantno praćenje, a u tom smislu ovaj rad može imati doprinos u očuvanju urbane sredine.Soils in the urban area are suspected to be contaminated with potentially toxic elements (PTEs), due to traffic, urbanisation, and industrialization. The possibility of adverse health effects and the exposure of children who spend a lot of time in playgrounds and playing with soil, has attracted a lot of attention in recent years, especially with regard to the potential risk to children's health. [1-2] The aim of this study was to determine the levels of arsenic (As), cadmium (Cd), lead (Pb), nickel (Ni), chromium (Cr), copper (Cu), and zinc (Zn) in 17 soil samples from different children's playgrounds in the city of Belgrade. The samples were prepared by acid assisted microwave digestion and the concentrations of elements were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES). Accuracy was assessed using the certified reference material NIST 2711a, and recoveries obtained were in the range of 80-120%. The average concentration of PTEs followed the following order: Zn (68.24 mg/kg) > Ni (60.99 mg/kg) > Cr (51.685 mg/kg) > Pb (21.615 mg/kg) > Cu (19.785 mg/kg) > As (8.1125 mg/kg) > Cd (0.1566 mg/kg). The average concentration of all metals in soil did not exceed the permissible limits according to the guidelines of Serbian legislation, the European Union (EU), and the World Health Organization (WHO). Since these PTEs can bioaccumulate and biomagnify in the food chain, their concentration in soil should be continuously monitored so this study should contribute to rising awareness for the protection of the urban environment. [1] M. Guney, G. J. Zagury, N. Dogan, T. T. Onay. Exposure assessment and risk characterization from trace elements following soil ingestion by children exposed to playgrounds, parks and picnic areas, J Hazard Mater 2010;182(1-3):656-64. [2] E. Schachter, A. Gailey, S. Perl Egendorf, H. W. Mielke, Mechanisms of children's soil exposure, Current Problems in Pediatric and Adolescent Health Care 2020, 50(1), 100742

    Modification of selectively acid-etched halloysite by mucoadhesive chitosan derivatives: New bionanocomposites with improved functional properties

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    In this study, the modification of selectively acid-etched halloysite (eHal) by low molecular weight chitosan (LChi) and its methacrylated derivative (MeLChi) is investigated to form new bionanocomposites with improved functional properties. The formation of nanocomposites was confirmed by various instrumental techniques (ζ-potential measurements, SEM, FT-IR, DSC, XRD and 1H NMR). Both nanocomposites exhibited improved functional properties while preserving the tubular structure of halloysite. The cytotoxic activity of eHal and eHal-polycation nanocomposites against normal human lung fibroblasts (MRC5) was determined using MTT assay. The results showed good biocompatibility of the prepared nanocomposites, with a cell survival rate of more than 90 %. The mucoadhesive properties of eHal and the corresponding chitosan nanocomposites were investigated in vitro. Primarily, ζ-potential measurements revealed electrostatic interactions between the eHal-polycation nanocomposites and mucin. The absorption study showed that the eHal-MeLChi nanocomposites could adsorb a greater amount of mucin (≈82 %) than the eHal-LChi nanocomposites (≈72 %) and eHal (≈58 %) after 8 h of incubation. Furthermore, the compacts of the tested samples were prepared by direct compression, and the detachment force against the mucin compact was measured using a texture analyzer. A significantly higher detachment force of the eHal-MeLChi nanocomposite compact (1.59 ± 0.07 N) from the mucin compact was determined compared to the eHal-LChi (1.35 ± 0.08 N) and eHal (0.98 ± 0.08 N) samples, demonstrating their improved mucoadhesive potential. In summary, this study demonstrates that functionalization of eHal with MeLChi may be a useful approach for the preparation of nanocomposites as potential carriers for mucoadhesive dosage forms

    Analiza trenda potrošnje lekova protiv gojaznosti i statusa na listama lekova koji se refundiraju – perspektiva odabranih evropskih zemalja

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    Obesity is a chronic, complex, relapsing disease impacting healthcare systems and the economy worldwide. We aim to analyze the utilization trends of antiobesity drugs, and their reimbursement status on drug lists of health insurance funds (HIF) in selected European countries. The DDD/1000 inhabitants/day methodology is used for utilization trend analysis, where data from official national utilization reports were used. For the reimbursement status analysis of 5 antiobesity drugs (orlistat, semaglutide, liraglutide, naltrexone/bupropion, setmelanotide), the websites of national health insurance funds (HIF) of 22 European countries were screened. Trend analysis revealed fluctuation for almost all antiobesity drugs (the highest decrease seen for orlistat in Serbia, and the highest increase for liraglutide in Croatia). Novel antiobesity drugs show an increasing utilization trend in almost all the countries. In two out of three European countries, antiobesity drugs are not covered by the HIF. Slovenia and Denmark reimburse most of the antiobesity drugs. The Netherlands is the only country where the cost of setmelanotide is paid by the HIF. Our results emphasize the importance of prioritizing the introduction and implementation of new strategies and reimbursement scheme models in global and national antiobesity policies.Gojaznost je hronična, kompleksna bolest koja se ponovo javlja (relaps) i utiče na zdravstvene sisteme i ekonomiju širom sveta. Cilj nam je da analiziramo trendove potrošnje lekova protiv gojaznosti, kao i status refundacije tih lekova na listama lekova fondova zdravstvenog osiguranja (FZO) u odabranim evropskim zemljama. Za analizu trenda potrošnje korišćena je metodologija DDD/1000 stanovnika/dan, gde su korišćeni podaci iz zvaničnih nacionalnih izveštaja o potrošnji. Za analizu statusa refundacije za 5 lekova protiv gojaznosti (orlistat, semaglutid, liraglutid, naltrekson/bupropion, setmelanotid), pregledani su sajtovi nacionalnih FZO u 22 evropske zemlje. Analiza trenda je otkrila fluktuacije za skoro sve lekove protiv gojaznosti (najveći pad zabeležen za orlistat u Srbiji, a najveći porast za liraglutid u Hrvatskoj). Novi lekovi protiv gojaznosti pokazuju trend rasta upotrebe u skoro svim zemljama. U dve od tri evropske zemlje lekove protiv gojaznosti ne pokriva FZO. Slovenija i Danska refundiraju troškove većine lekova protiv gojaznosti. Holandija je jedina zemlja u kojoj trošak setmelanotida plaća FZO. Naši rezultati naglašavaju važnost davanja prioriteta uvođenju i implementaciji novih strategija i modela šema refundacije u globalnim i nacionalnim politikama usmerenim protiv gojaznosti

    Butyrate- and Beta-Hydroxybutyrate-Mediated Effects of Interventions with Pro- and Prebiotics, Fasting, and Caloric Restrictions on Depression: A Systematic Review and Meta-Analysis

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    To examine the butyrate- and beta-hydroxybutyrate (BHB)-modulated effects of pre- and probiotic interventions, fasting, and caloric restriction interventions, a systematic literature review was carried out with a subsequent meta-analysis. Three pre-and probiotic intervention randomized control trials (RCTs) were included in the meta-analysis. A significant increase in butyrate (standardized mean difference (SMD) [confidence interval (CI)] 0.34; [0.02–0.67]) and an improvement in depression scores (SMD [CI] 0.15, [−0.35–0.70]) through pre- and probiotic interventions were shown in the meta-analysis. The intervention duration of the included studies ranged from three days to four weeks, with the examined population being healthy adults. Butyrate was measured in either plasma or feces, and the depression score was obtained under the Swedish core affect scale, the hospital anxiety and depression scale (HADS), or the depression, anxiety, and stress scale—21 items (DASS-21). In addition to butyrate, the total SCFA concentration also seems to be positively associated with pre- and probiotic administration (SMD [CI] 0.55 [0.15–0.95]). Despite the significant short-chain fatty acid (SCFA) and butyrate concentration changes, no significant correlation between butyrate and depression or between SCFAs and depression could be shown through linear regression models. Nevertheless, the regression coefficient b1 = 1.57 (p = 0.17) for butyrate suggests a strong, positive connection between butyrate and depression. Additionally, three studies were qualitatively analyzed, examining fasting as an intervention and revealing a connection between fasting, BHB, and depression. The association between fasting, BHB, and depression or mood elevation appeared to be related to BHB concentrations, which may be due to the similar biochemical properties of BHB and butyrate. Furthermore, caloric restrictions as alternatives to fasting were proposed as potential long-term interventions

    Educational models in Pharmacy: Evolution and historical perspectives in BENU Pharmacies across Serbia

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    Educational models in pharmacy represent crucial strategies and processes shaping the development and education of pharmaceutical professionals within BENU pharmacies across Serbia, which currently number over 450 locations. This paper explores the evolution of these models through four key phases, focusing on various aspects of learning and development crucial for continuously improving the quality of pharmaceutical services. In the first phase, from 2004 to 2010, educational models relied on traditional learning methods such as lectures and independent study. These models aimed to transfer fundamental knowledge in pharmacy, ethics, and administration, providing pharmacists with solid foundations for their professional practice in the pharmacy environment. The second phase, lasting from 2011 to 2015, introduced interactive learning methods such as workshops, team projects, and case studies. These models allowed pharmacists to gain practical experience and skills through active participation and the application of theoretical knowledge in real-life situations, enhancing their practical skills and efficiency in delivering pharmaceutical services. 134 The third phase, from 2016 to 2020, marked a shift towards personalized and individualized training approaches such as coaching, mentoring, and leadership development programs. Educational models in this phase focused on supporting personal development and achieving professional goals for each pharmacist, providing them with tools and resources for continuous improvement of their skills and competencies. The fourth phase, starting from 2021, brought innovative approaches such as digital education, e-learning, and virtual simulations. These models enabled pharmacists to access the latest information and technologies in real-time, improving their ability to quickly respond to industry changes and deliver excellent patient care. With the increasing number of pharmacies and changes in environmental requirements, educational models in BENU pharmacies in Serbia continuously adapt to meet the dynamic challenges of the pharmaceutical sector and enhance service quality for patients. This evolution not only highlights advancements in educational practices but also underscores the pivotal role of continuous learning and development in maintaining expertise and service quality in the pharmaceutical industry

    A vision to the future: Value-based laboratory medicine

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    The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine"(Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future

    Design and ADMET prediction of novel dual inhibitors from the histone deacetylase family

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    The family of histone deacetylases (HDAC) has been associated with various processes in the development and growth of many cancers. Selective inhibition improves the tolerability of HDAC inhibitors, while dual targeting of synergistic targets improves the efficacy of cancer therapy. In this article, we report the design, molecular docking studies and ADMET predictions of nine novel HDAC6/WEE1, HDAC6/GLS1 and SIRT2/AURKA dual inhibitors. The developed compounds show comparable or better docking results and ADMET properties than reference co-crystal ligands.17th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 23-27, 2024 Belgrade, Serbi

    Determination of IGG anti-oxLDL antibody levels in patients with ST-segment elevation acute myocardial infarction

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    Studije novijeg datuma sugerišu da pored dislipidemije, inflamacije i oksidativnog stresa, u nastanku i razvoju ateroskleroze učestvuju i imunski procesi. Dobro je poznato da oksidovani lipoprotein niske gustine (oxLDL) podstiče proizvodnju autoantitela, što rezultira formiranjem imunskih kompleksa koji sadrže oxLDL. Izolovana autoantitela pretežno su G izotipa i usmerena su protiv različitih epitopa na oxLDL. U praksi se smatraju markerima prisustva oxLDL, ali njihova uloga u nastanku i progresiji ateroskleroze još uvek nije rasvetljena. Ova studija imala je za cilj da odredi koncentracije autoantitela G klase na oxLDL (IgG anti-oxLDL antitela) u serumu kod bolesnika sa akutnim infarktom miokarda sa elevacijom ST segmenta (STEMI) i da istraži njihovu povezanost sa rizičnim LDL i HDL fenotipom. Kod 69 STEMI bolesnika i 67 zdravih kontrolnih ispitanika, IgG antioxLDL antitela su određena korišćenjem komercijalno dostupnog ELISA kita (OLAB IgG Anti Oxidized Low Density Lipoprotein, Biomedica Medizinprodukte GmbH & Co KG, A-1210 Wien, Austria) prema preporukama proizvođača. Razdvajanje HDL i LDL subklasa izvršeno je poliakrilamid gradijent gel elektroforezom. Osim toga, određeni su i relativni udeli četiri LDL subklase (LDL I, LDL II, LDL III, LDL IV) i dve glavne HDL subklase (HDL 2, HDL 3). Kriterijum za definisanje rizičnog LDL B fenotipa i fenotipa malih HDL čestica bio je dominantni prečnik LDL čestica ≤ 25,5 nm, odn. dominantni prečnik HDL čestica ≤ 8,8 nm. Istovremeno, primenom standardnih biohemijskih metoda određeni su i drugi biohemijski parametri (glukoza, trigliceridi, ukupni holesterol, HDL-holesterol i LDL-holesterol). Rezultati ove studije nisu pokazali postojanje statistički značajne razlike u koncentracijama IgG anti-oxLDL antitela između STEMI bolesnika i zdravih kontrolnih ispitanika (p>0,05). Međutim, nađeno je da su kontrolni ispitanici sa povećanim udelom malih HDL i LDL čestica imali više koncentracije IgG anti-oxLDL antitela (p<0,05), što sugeriše da se oksidativna modifikacija LDL čestica i posledično povećana produkcija IgG anti-oxLDL antitela lakše dešavaju kod zdravih osoba sa nepovoljnim lipidnim profilom. Istovetna analiza kod STEMI bolesnika nije otkrila razlike u koncentracijama IgG anti-oxLDL antitela (p>0,05), što bi se moglo objasniti naknadnim formiranjem nerastvorljivih imunskih kompleksa koji sadrže oxLDL i njihovim deponovanjem u tkivima. Dobijeni rezultati podržavaju hipotezu dualističke uloge IgG anti-oxLDL antitela, odnosno mogućnost da ova antitela imaju zaštitnu ulogu kod zdravih osoba i proaterogenu ulogu u uznapredovaloj aterosklerozi karakterističnoj za STEMI.Recent studies suggest that in addition to dyslipidemia, inflammation and oxidative stress, immune processes are also involved in the formation and development of atherosclerosis. It is known that circulating oxidized low-density lipoprotein (oxLDL) triggers the production of autoantibodies, leading to the formation of oxLDL- containing immune complexes (oxLDL-IC). Isolated human anti-oxLDL antibodies are predominantly of the IgG isotype and are directed against various epi- topes in oxLDL. In practice, these antibodies are con- sidered markers for oxLDL, but their role in the devel- opment and progression of atherosclerosis has remained controversial to date. The aim of this study was to determine serum levels of human class G anti- bodies against oxLDL (IgG anti- oxLDL antibodies) in patients with ST-segment elevation acute myocardial infarction (STEMI) and to investigate their association with low-density lipoprotein (LDL) and high-density lipoprotein (HDL) risk phenotypes. IgG anti-oxLDL antibodies were determined in 69 STEMI patients and 67 healthy volunteers using a commercially available ELISA kit (OLAB IgG Anti Oxidized Low Density Lipoprotein, Biomedica Medizinprodukte GmbH & Co KG, A-1210 Vienna, Austria). The separation of HDL and LDL subclasses was performed by polyacrylamide gradient gel electrophoresis. In addition, the relative proportions of four LDL subclasses (LDL I, LDL II, LDL III and LDL IV) and two main HDL subclasses (HDL 2 and HDL 3) were determined. LDL phenotype B was defined when the dominant LDL particle diameter was ≤ 25.5 nm. Similarly, the predominant HDL particle diameter ≤ 8.8 nm was the criterion for defining a small-format HDL phenotype (HDL 3 phenotype). At the same time, other biochemical parameters (glu- cose, triglycerides (TG), total cholesterol (TC), high- density lipoprotein cholesterol (HDL-C) and low- den- sity lipoprotein cholesterol (LDL-C)) were measured using standard biochemical methods. The results showed no significant difference in IgG anti-oxLDL antibody levels between patients and the control group (p>0.05). However, our study provided the interesting finding that control subjects with a higher proportion of small HDL and LDL particles had increased IgG anti- oxLDL antibody levels (p<0.05), suggesting that oxidative modifications of LDL and the consequent increased production of IgG anti-oxLDL antibodies occur more readily in healthy individuals with an unfa- vorable lipid profile. The same analysis in STEMI patients revealed no differences in IgG anti-oxLDL antibody levels (p>0.05), which could be explained by the subsequent formation of insoluble immune com- plexes, oxLDL-IC, which are deposited in the tissue. The results obtained support the concept of the dual- istic role of IgG anti-oxLDL antibodies, i.e. the possibil- ity that these antibodies play a protective role in healthy individuals and a proatherogenic role in advanced atherosclerosis, as is the case in our STEMI group.Međunarodni XXIII srpski kongres medicinske biohemije i laboratorijske medicine, 16-18. septembar 2024. godine, Posterske sekcij

    Asymmetric Introgression and Cryptic Natural Hybridization between Two Species of Teucrium Section Polium (Lamiaceae) on the Balkan Peninsula

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    In this work, we analyzed the morphology and genetic structure of Teucrium montanum, T. capitatum and their hybrid T. × rohlenae from three syntopic populations. A morphometric study showed that the parents and their hybrids exhibited continuous morphological variation, with the hybrid positioned exactly between the parents. Genetic analysis revealed that plants morphologically identified as T. × rohlenae are fertile hybrids that produce hybrid swarms dominated by later-generation hybrids. This suggests that introgression, rather than speciation, is the more likely outcome of hybridization between these plant species. The extent and direction of gene flow between the two species differed markedly between the three syntopic localities. At the Trilj locality, it was clearly unidirectional, with T. capitatum playing the dominant role. At the Sićevo locality, gene flow was slightly asymmetric, favoring the genetic background of T. capitatum, while at the Sliven site, it was completely asymmetric in the opposite direction. The extreme case of unidirectional gene flow was observed at the Trilj locality where plants morphologically identified as T. montanum could not be genetically distinguished from T. capitatum. This suggests that interspecific hybridization occurred long ago, leading to introgression and cryptic hybrids, blurring of species boundaries and generating evolutionary noise

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