Cd, Cr, and Pb concentrations were analysed in 18 bottled drinking water samples from the Bosnia and Herzegovina (B&H) market, classified as natural spring water or still natural mineral water. Metal concentrations were determined using atomic absorption spectrometry with electrothermal atomisation in a graphite furnace. Cr was quantified in two samples, Pb in four samples, while Cd concentrations were below the limit of detection in all samples. All concentrations were below national regulatory limits. Health risks associated with Cr and Pb exposure through bottled water consumption were assessed for adolescents, adults, and pregnant women by calculating the hazard quotient (HQ), hazard index (HI), carcinogenic risk (CR), and total carcinogenic risk (TCR). Some exposure scenarios exceeded HQ and HI thresholds, suggesting potential non-carcinogenic effects, primarily due to Pb exposure. CR and TCR values across all exposure scenarios were below established thresholds, indicating generally acceptable or negligible carcinogenic risk. Given the limited sample set, the data on Cd, Cr, and Pb content, along with the health risk assessment, should be regarded as preliminary, serving as a starting point to guide future research. Considering the health implications of heavy metal exposure, continuous water-quality monitoring and a more comprehensive health risk assessment, including additional heavy metals and a larger sample set, are essential, as regulatory compliance does not necessarily imply the absence of health risks.

Phenylenediamine (PPD) is an aromatic amine used as a precursor in oxidative permanent hair dyes, with a maximum allowed concentration of 2

Antimicrobial resistance is currently one of the greatest challenges to health. Resistant bacterial infections affect clinical and therapeutic outcomes in patients, resulting in increased mortality, morbidity, prolonged hospitalization and higher treatment costs. It is expected to be the leading cause of death by 2050. Carbon nanomaterials have great potential in the treatment of bacterial antimicrobial resistance, with quantum dots being the most promising. Carbon quantum dots (CQD) have excellent properties such as low toxicity, high biocompatibility and solubility in physiological fluids. Raw materials for their synthesis are diverse, environmentally friendly and easily available. They can have antibacterial effects in several ways, the most important of which is the production of reactive oxygen species and the resulting damage to bacterial cell wall and metabolism. To overcome the limitations in terms of their agglomeration and poor stability, CQD can be conjugated with various materials such as semiconductors and metals, leading to the formation of conjugates with stronger and wider antibacterial activity and weaker resistance development. CQD can also be conjugated with antibiotics and enhance their activity. In the future, the synthesis of new and more effective quantum dots is expected, which should find application in clinical practice.

Cornus mas L. is traditionally used for various medicinal purposes, although systematic data on its pharmacognostic properties are still limited. Considerable variation was observed among plant organs, so phenolic and flavonoid content varied by plant part, with location-related differences among samples, with the highest in leaf and fruit from Bijeljina and the lowest in leaf from Sarajevo. Antioxidant activity was much better in leaf and bark than in fruit. Extracts inhibited ESBL-producing Escherichia coli, with MICs mainly at 125 µg/mL; bark extract (Tuzla) showed 250 µg/mL and reduced biofilm formation. Leaf and bark extracts showed dose-dependent cytotoxicity against PC-9, MCF-7, and MDA-MB-231 cells, while fruit extracts were weaker. In human lymphocytes, bark (Bileća) and leaf (Tuzla) extracts decreased nuclear division and induced micronuclei at 200 µg/mL. Molecular docking indicated strong bacterial target binding for loganin and cornuside, supporting the antibacterial and antitumor potential of C. mas.

OBJECTIVES:The primary aim of this study is to detect and quantify the presence of Sildenafil (SDF) and Tadalafil (TDF) in dietary supplements marketed as natural sexual enhancers in Bosnia and Herzegovina. Additionally, the study seeks to utilize these findings to inform relevant authorities, enabling further testing in reference laboratories and prompting the necessary actions to remove these adulterated products from the market. METHODS:Using high-performance liquid chromatography with diode array detection (HPLC-DAD), 20 samples were analysed for the PDE-5 inhibitors. RESULTS:The analysis revealed that seven of the samples contained either SDF or TDF, with mean concentrations ± standard deviation (SD) ranging from 2,075.57 ± 0.47 µg/g to 33,808.857 ± 99.43 µg/g, and TDF concentrations ranging from 24.16 ± 0.11 µg/g to 3,994.66 ± 6.95 µg/g. CONCLUSION:These findings indicate a significant health risk posed by the adulteration of these products. The widespread presence of these active pharmaceutical ingredients (APIs) in products falsely labelled as natural underscores the urgent need for stringent regulatory oversight and enhanced quality control measures to protect consumer safety. This study adds to the growing body of evidence concerning the adulteration of dietary supplements and emphasizes the critical importance of regulatory compliance and monitoring in safeguarding public health.

Autism spectrum disorder (ASD) as a neurological disorder can result from the interaction of genetic and environmental factors such as air pollution and exposure to chemical pollutants. This study tested the hypothesis that living in areas near petrochemical industries and exposure to benzene, toluene, ethylbenzene, and xylene (BTEX) may adversely affect maternal and fetal health and increase the risk of autism. We conducted a prospective cohort study from 2019 to 2024, following 110 pregnant women divided into exposure and control groups, along with 145 children born during the study [exposure group (n = 80) and control group (n = 65)]. Prenatal urinary BTEX concentrations were measured using gas chromatography-mass spectrometry (GC/MS). The MCHAT-R/F screening tool was used to track the child's behavior in terms of the occurrence of autism spectrum symptoms. The results showed that the mean concentration of prenatal BTEX urine concentration in the exposed group (557 ng/l) was significantly higher than that in the control group (258 ng/l). The M-CHAT-R/F screening indicated moderate ASD risk in six exposure group children and three control group children; and high ASD risk for four exposure group children and one control group child. The findings in the exposure group revealed a higher incidence of ASD among boys compared to girls (4:2 in medium risk and 3:1 in high risk). Multivariate logistic regression analysis indicated that the prevalence of autism in the exposed group was significantly associated with exposure to benzene (OR, 2.10; 95%CI, 1.93-2.17; Pvalue<0.05) and toluene (OR, 1.7; 95%CI, 1.62-1.81; Pvalue<0.05). Living in industrial areas and perinatal exposure to BTEX compounds may increase the risk of ASD. Therefore, health impact assessment studies focusing on the health of vulnerable groups before the construction of petrochemical industries, as well as the monitoring of relevant health indices during the operational phase, should be prioritized.

Background Systematic reviews (SR), an evidence-synthesis tool, have been increasingly used in toxicology, for regulatory decision-making and allocation of research funding resources. A critical domain of methodological quality is publicly available in the SR protocol that describes the review methods prior to the review. Earlier work showed that only a small number of published SRs in environmental health had identifiable protocols, but did not evaluate their completeness of reporting. Thus, there is a critical need to assess the number of protocols published in peer-reviewed literature related to environmental/occupational toxicology and how much those SR protocols adhere to current reporting standards such as PRISMA-P.Objective The overarching objective of this review is to assess the reporting quality of SR protocols in environmental and occupational toxicology, published in peer-reviewed journals.Methods and analysis This protocol has been reported following PRISMA-P and PRISMA-S checklist and study selection, data extraction, and reporting quality assessment were piloted by independent reviewers. Four electronic databases (PubMed, Scopus, Web of Science, EMBASE) were selected and will be searched for SR protocols using pre-defined strings. Both title/abstract and full-text screening will follow detailed eligibility criteria based on the population concept context (PCC) framework. We will include peer-reviewed, self-identified SR protocols that aim to assess the adverse effects of environmental and occupational exposures. We will perform data extraction using the form that includes general bibliographic information, exposure, adverse effect information, evidence streams, and guidelines/checklists used in protocol reporting or development. A reporting assessment form consisting of 15 PRISMA-P-based items, of which eleven with identical binary responses (reported vs not reported) address critical elements of SR protocol. Assessments of the eleven quality items will provide data for the analysis of the reporting quality of SR protocols. We employ reporting quality as it provides a practical and suitable approach to evaluating the inclusion of essential SR elements, under the assumption that these elements would be reported if they had been appropriately planned rather than overlooked. The screening and data extraction will be conducted by two independent reviewers. Disagreements will be discussed if needed with the support of a third reviewer. The data analysis will describe the total number of SR protocols and trends over time, and absolute frequencies and/or proportion of bibliographic information items. It will summarize the reporting quality of all included protocols by a histogram and rank the quality criteria by their level of adherence across the included protocols.

Our previous research demonstrated that LPQNIPPL and LPβ3hQNIPPL peptides are degraded in vitro by DPP-4 enzyme. Besides the expected degradation products, additional degradation products were observed on HPLC-MS chromatograms, suggesting cleavage of both the C- and N-terminal amino acids. Molecular docking provided a model for the observed carboxypeptidase, but not for aminopeptidase activity. Compared to conventional N-terminal binding at the active site, the obtained carboxypeptidase model suggested the α-amino group interaction with S2 subsite, C-terminal amino acid side chain interaction with the S1 subsite, reversed peptide backbone order and P1' proline in a secondary peptide bond. The scissile bond position and distance relative to the active Ser630 seems to remain similar compared to conventional binding. Efficient C-terminal binding to the DPP-4 active site is reinforced by molecular dynamics results, but with altered interactions compared to molecular docking after ligand adaptation phase. Although peptide interactions and distance of scissile bond from the DPP-4 nucleophile Ser630 appears to support the cleavage model, the required nucleophilic attack angles are not confirmed. The proposed model does not allow final conclusions on nucleophilic attack stereochemistry but opens the discussion on possible DPP-4 carboxypeptidase cleavage of peptides, as well as retro/retro-inverso peptides with C-terminal Leu-NH2.

Dietary acrylamide exposure potentially poses health risks, including increased cancer risk and neurotoxic effects. There is no official data on acrylamide levels in food products on the Bosnia and Herzegovina (B&H) market, making it challenging to assess the associated health risks. As a non-EU country, B&H lacks national regulations aligned with Commission Regulation (EU) 2017/2158, which establishes benchmark levels and mitigation measures for acrylamide. This study used GC-MS to assess acrylamide content in fifteen food products from the B&H market, categorised as potato crisps/sticks, biscuits/wafers, and coffee. Acrylamide levels in some potato crisps and sticks, tea rings, and plain biscuits exceeded benchmark values, while levels in butter biscuits, biscuits with inclusions, filling or coating, wafers, and instant coffee, remained within acceptable limits. The highest acrylamide level was in potato sticks (1048.3 μg/kg), and the lowest in butter biscuits (23.8 μg/kg). Potato crisps/sticks had the highest average acrylamide levels (677.5 μg/kg), followed by tea rings and plain biscuits (444.5 μg/kg). Potato-based snacks accounted for the highest estimated dietary acrylamide intake. Most products exceeding benchmark levels originated from B&H, suggesting local producers might not fully apply mitigation strategies. These findings emphasise the need for regulatory reform, regular market monitoring, and targeted mitigation efforts.

Solvent and substitution effects on the UV/Vis spectroscopic and fluorescence behaviour of seven synthesized 3-substituted 4-hydroxycoumarin derivatives were tested. The tested compounds were dissolved in ethyl acetate, acetonitrile, and dimethyl sulfoxide. Absorption and emission spectra were recorded in the range of 200–800 nm. All tested 4-hydroxycoumarin derivatives showed good absorption in a wide range of 200–550 nm, depending on the properties of the substituents on the benzene ring of the cinnamoyl moiety and the type of solvent. In comparison to the unsubstituted analogue, compounds with an electron-donating group exhibited bathochromically shifted UV/Vis absorption and emission spectra. The highest fluorescence quantum yield was observed for compounds with dimethylamino and acetamido groups as substituents at the benzene ring. Considering that both substitution and solvent affect the absorption and emission spectra of the tested compounds, it can be concluded that judiciously selecting these parameters can improve their absorption and fluorescence properties, making them suitable for various analytical uses.

BACKGROUND:Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE:This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS:Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS:Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION:The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data.

BACKGROUND: Preclinical drug testing requires in vitro and in vivo assessments that are vital for studying drug pharmacokinetics and toxicity. Distinct factors that play an important role in drug screening, such as hydrophobicity, solubility of the substance and serum protein binding can be challenging by inducing result inconsistencies. Hence, establishing accurate methods to quantify drug concentrations in cell cultures becomes pivotal for reliable and reproducible results important for in vivo dosing predictions. OBJECTIVE: This research focuses on developing an optimized analytical approach via high-pressure liquid chromatography (HPLC) to determine thymoquinone (TQ) levels in monolayer cell cultures. METHODS: The method’s validation adheres to the International Council for Harmonisation (ICH) guideline M10, ensuring its acceptance and applicability. Using an HPLC system with a Diode Array Detector (DAD), the study fine-tuned various parameters to achieve an efficient separation of TQ. Validation covered specificity, sensitivity, matrix effects, linearity, precision, and accuracy, alongside assessing TQ stability in RPMI-1640 medium. RESULTS: The HPLC method exhibited remarkable TQ specificity, free from interfering peaks at the analyte retention. Sensitivity analysis at the lower limit of quantification (LLOQ) revealed 5.68% %CV and 98.37% % mean accuracy. Matrix effect evaluation showcased accuracy within 85–115%. Linearity spanned in the concentration range of 2–10 μM with a correlation coefficient (r2) of 0.9993. Precision and accuracy were aligned with acceptance criteria. The proposed method was found to be greener in terms of usage of persistent, bioaccumulative, and toxic chemicals and solvents, corrosive samples, and waste production. CONCLUSION: The developed HPLC-DAD method emerges as specific, accurate, sensitive, and reliable for TQ determination in cell cultures. It ensures robust TQ quantification, enhancing precise in vitro assessments and dependable dosing predictions for in vivo studies. Further research is advocated to investigate TQ’s stability across diverse environmental conditions.

Skin sensitization is a crucial endpoint in the safety assessment of chemicals, with the Direct Peptide Reactivity Assay (DPRA) emerging as a valuable in chemico method for evaluating a substance's sensitization potential. This review delves into the principles, applicability, and limitations of the DPRA within the context of the Adverse Outcome Pathway (AOP) framework for skin sensitization. We examine the DPRA'srole in addressing the molecular initiating event of skin sensitization, its integration into Integrated Approaches to Testing and Assessment (IATA), and its performance in predicting sensitizers. The review also highlights the challenges in testing certain categories of chemicals and the importance of considering the DPRA's results alongside other complementary methods. By providing a comprehensive overview of the DPRA, this review aims to inform researchers, regulators, and clinicians about its utility and limitations in the context of skin sensitization testing.

Objective:Iris species are widely used in pharmaceutical and cosmetic applications owing to their high content of bioactive compounds with anti-inflammatory and antimicrobial properties. This study aimed to investigate the potential antibacterial effect of crude extracts (aqueous, 50% and 80% ethanol) of three Iris species (I. pumila, while I. reichenbachii and I. illyrica are endemic) from Bosnia and Herzegovina against the multiresistant bacterial strain methicillin-resistant Staphylococcus aureus subsp. aureus ATCC 33591 (MRSA strain).Materials and Methods: The antimicrobial compounds in the crude extracts were identified using High-performance liquid chromatography (HPLC), and their effects on the MRSA strain were tested using agar well diffusion and broth microdilution method. The binding affinities were analysed using molecular docking simulations.Results: We identified bioactive targeted compounds in these extracts, mainly flavonoids named isorhamnetin, hesperidin, quercetin, fisetin, genistein, and kaempferol. Antibacterial assays showed that extracts of all three Iris species inhibited MRSA. The binding affinity analysis showed that isorhamnetin and hesperidin had the highest affinity scores, stronger (isorhamnetin) or the same (hesperidin) as the positive control ceftobiprole.Conclusion: Thisin vitro and in silico study showed that Iris species represent a valuable source of bioactive compounds that can be used against multidrug-resistant strains such as MRSA. The potential use of these agents in multiple drugs is warranted, and further evaluation for human application is needed.

Morus alba L. is a plant with a long history of dietary and medicinal uses. We hypothesized that M. alba possesses a significant biological potential. In that sense, we aimed to generate the chemical, antimicrobial, toxicological, and molecular profile of M. alba leaf and fruit extracts. Our results showed that extracts were rich in vitamin C, phenols, and flavonoids, with quercetin and pterostilbene concentrated in the leaf, while fisetin, hesperidin, resveratrol, and luteolin were detected in fruit. Extracts exhibited antimicrobial activity against all tested bacteria, including multidrug-resistant strains. The widest inhibition zones were in Staphylococcus aureus ATCC 33591. The values of the minimum inhibitory concentration ranged from 15.62 μg/ml in Enterococcus faecalis to 500 μg/ml in several bacteria. Minimum bactericidal concentration ranged from 31.25 μg/ml to 1000 μg/ml. Extracts impacted the biofilm formation in a concentration-dependent and species-specific manner. A significant difference in the frequency of nucleoplasmic bridges between the methanolic extract of fruit (0.5 μg/ml, 1 μg/ml, 2 μg/ml), as well as for the frequency of micronuclei between ethanolic extract of leaf (2 μg/ml) and the control group was observed. Molecular docking suggested that hesperidin possesses the highest binding affinity for multidrug efflux transporter AcrB and acyl-PBP2a from MRSA, as well as for the SARS-CoV-2 Mpro. This study, by complementing previous research in this field, gives new insights that could be of great value in obtaining a more comprehensive picture of the Morus alba L. bioactive potential, chemical composition, antimicrobial and toxicological features, as well as molecular profile.

BackgroundThe global coronavirus 2019 (COVID-19) pandemic began in early 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mid-2020 the CIAO (Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway Framework) project was established, bringing together over 75 interdisciplinary scientists worldwide to collaboratively investigate the underlying biological mechanisms of COVID-19 and consolidate the data using the Adverse Outcome Pathway (AOP) Framework. Neurological symptoms such as anosmia and encephalitis have been frequently reported to be associated with infection with SARS-CoV-2.ObjectiveWithin CIAO, a working group was formed to conduct a systematic scoping review of COVID-19 and its related neurological symptoms to determine which key events and modulating factors are most commonly reported and to identify knowledge gaps.DesignLitCOVID was used to retrieve 86,075 papers of which 10,244 contained relevant keywords. After title and abstract screening, 2,328 remained and their full texts were reviewed based on predefined inclusion and exclusion criteria. 991 studies fulfilled the inclusion criteria and were retrieved to conduct knowledge synthesis.ResultsThe majority of publications reported human observational studies. Early key events were less likely to be reported compared to middle and late key events/adverse outcomes. The majority of modulating factors described related to age or sex. Less recognised COVID-19 associated AO or neurological effects of COVID-19 were also identified including multiple sclerosis/demyelination, neurodegeneration/cognitive effects and peripheral neuronal effects.ConclusionThere were many methodological and reporting issues noted in the reviewed studies. In particular, publication abstracts would benefit from clearer reporting of the methods and endpoints used and the key findings, to ensure relevant papers are included when systematic reviews are conducted. The information extracted from the scoping review may be useful in understanding the mechanisms of neurological effects of COVID-19 and to further develop or support existing AOPs linking COVID-19 and its neurological key events and adverse outcomes. Further evaluation of the less recognised COVID-19 effects is needed.

OBJECTIVE:The aim of this study was to investigate students' knowledge, attitudes and hesitancy regarding COVID-19 vaccination.METHODS:A cross-sectional questionnaire-based survey was conducted among a total of 1282 medical students and 509 non-medical students at four public universities in Bosnia and Herzegovina: Tuzla, Sarajevo, Banja Luka, and Mostar.RESULTS:A significantly higher rate of vaccination was observed in the group of medical students as well as a higher level of knowledge about vaccination in general and vaccines against the COVID-19 disease. Students who received the COVID-19 vaccine had a higher level of knowledge about vaccination in general and COVID-19 vaccines in particular compared to the non-vaccinated students in the medical and non-medical groups, respectively. Furthermore, vaccinated students, regardless of the course they are taking, showed generally stronger positive attitudes compared to non-vaccinated students, regarding the safety and effectiveness of the COVID-19 vaccine. Both groups of students believe that the rapid development of the vaccine is contributing to refusal or hesitancy to receive a vaccine against COVID-19. Social media/networks were the main sources of information about the COVID-19 vaccine. We did not find any contribution of social media to the reduced level of COVID-19 vaccine coverage.CONCLUSION:Education of students about the benefits of the COVID-19 vaccine will lead to its better acceptance as well as the development of more positive attitudes towards vaccination in general, especially having in mind that students are the future population of parents, who will make decisions about vaccinating their children.

In order to raise and harmonize the quality standards of pharmaceutical studies at the national level of Bosnia and Herzegovina and thus get closer to the implementation and quality assurance of study programs of EU countries, a team of professors from the University of Sarajevo-Faculty of Pharmacy prepared and was awarded the Erasmus+ project IQPharm. IQPharm (Innovating quality assessment tools for pharmacy studies in Bosnia and Herzegovina) aims at capacity building of quality management, and aims to introduce new tools for quality improvement, digitization and modernization of pharmacy studies at public universities in Bosnia and Herzegovina, including strengthening semi-structured experiential education in line with EU standards and higher education regulations for regulated professions. The introduction of new tools for the assessment of the quality of study programs (KREF) enables the development of evidence-based recommendations for change, modification and innovation of existing methods of knowledge transfer, didactic approaches and curricula. The introduction of a new system of proficiency testing through experiential education (OSCE) sets equal standards at the national level for the learning outcomes of graduate pharmacists. The development of E-platform ensures the digitization and modernization of experiential education management. Experiential education at the level of Bosnia and Herzegovina will be significantly improved through the introduction of the E-platform, by raising the standards of the practice itself and facilitating its implementation by student services, students and their mentors. A special part of this project is the development of free modules, which are extracurricular subjects intended to enrich the knowledge of students and graduates of pharmacy, They should track the labor market trends, and thus make higher education more agile and attractive.