Neutral bis(amino acidato)copper(II) [Cu(aa)] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa), two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa) compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa) calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa) compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa) in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling.

As healthcare workers run a high and constant occupational risk of hepatitis B virus (HBV) infection through exposure to biological material, vaccination is mandatory as well as the monitoring of antibody levels one to two months after complete immunisation. The aim of this descriptive cross-sectional study was to determine HBV vaccine coverage of 200 primary and secondary healthcare workers (100 each) from Šabac, Serbia and their blood anti-HBs titre. We also wanted to identify factors that could predict the titre. Anti-HBV vaccination covered all participants, of whom 89.5 % were fully vaccinated, and 85 % had a protective antibody titre. We found a statistically significant association between antibody titre and the number of received vaccine doses, chronic jaundice, autoimmune disease, and cancer in our participants. The fact that 15 % did not achieve the protective antibody titre confirms the necessity of its control after immunisation, which is not routinely carried out in most countries, Serbia included. It is, therefore, necessary to develop a detailed strategy for monitoring vaccination and serological status of healthcare workers in order to improve their safety at work. An important role should also be given to continuous education of healthcare workers from the beginning of schooling to the end of their professional career.

The aim of this study was to investigate and compare justice sensitivity between self-perceived beneficiaries, victims, and observers in a sample of 90 healthcare workers (nurses and physiotherapists) at the Varaždinske Toplice Special Medical Rehabilitation Hospital, Croatia. For this purpose we used a questionnaire consisting of demographic data and the Croatian version of the justice sensitivity inventory developed by Schmitt. Regardless of its limitations, our study clearly shows that healthcare professionals at Varaždinske Toplice are most sensitive to injustice from the beneficiary's perspective, that is, as persons who personally benefitted from injustice, although they may not have been instrumental to this effect. They are less sensitive to injustice perceived on the outside (observer's perspective) or to injustice suffered by themselves (victim's perspective). Another important finding is that participants of female gender, rural residence, and nurses (who are all women) are significantly more sensitive to injustice, whereas age and marital status do not seem to contribute to justice sensitivity. Future research should investigate the perception of injustice over a longer timeframe and involve all healthcare workers. It could also address different approaches to management, especially in terms of worker rewards and career advancement. Qualitative research among healthcare workers could provide a broader and clearer idea of social injustice at their workplace.

The aim of this study was to investigate the extent of second-hand smoke exposure in younger population visiting nightclubs in Croatia by comparing the levels of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine (3HC) in urine samples taken from 22 participants before and after spending about three hours in a nightclub, stratified by smoking status (smokers and non-smokers). The samples were prepared by liquid-liquid extraction and analysed with gas chromatography-mass spectrometry. The presence of nicotine, cotinine, and 3HC was confirmed in all urine samples. Their median concentrations significantly differed between the two measurements in non-smokers. Our findings show that even a three-hour exposure to second-hand smoke can significantly increase the levels of nicotine and its metabolites in urine, which are indicative of exposure to other, harmful tobacco smoke substances. They also call for raising awareness of the health risks of exposure to second-hand smoke in the general population and among individuals who frequent nightclubs in particular.

Occupational health and safety (OHS) policies in healthcare institutions must be well managed, because healthcare practice involves many physical, biological, ergonomic, chemical, and psychosocial hazards that can affect the health of healthcare workers. In addition, their work performance may be affected by the so-called organisational myopia. In this context, the aim of our study was to determine how organisational myopia affects OHS practices in healthcare institutions and whether it increases the risk of occupational accidents. The study population consisted of a convenience sample of 420 healthcare professionals working throughout Turkey who completed a questionnaire addressing these three domains: organisational myopia, OHS practices, and risk of occupational accidents. Their responses were analysed with exploratory factor analysis, reliability analysis, and Spearman's correlation to assess the adequacy of measurement tools and identify relationships between variables, followed by mediation analysis. We found that OHS practices mitigate organisational myopia and the risk of occupational accidents. We also found no significant effect of organisational myopia on the risk of occupational accidents. Our findings underscore the importance of OHS practices in healthcare institutions and that organisational myopia should be evaluated in special contexts such as working time, experience, or routinisation.

The aim of this cross-sectional field study was to establish the condition of hand and forearm skin barrier among dentists and physicians and how it may be associated with personal and work-related factors. The study consisted of an occupational questionnaire, clinical examination of skin on hands, and transepidermal water loss (TEWL) and pH measurements on hands and forearms. The participants were divided in the following groups (N=37 each, N=148 in total): physicians, medical surgeons, dentists, and dental surgeons. We calculated the difference between hand and forearm TEWL and pH (ΔTEWL and ΔpH, respectively) and divided it by the forearm values (ΔTEWL% and ΔpH%, respectively). There was a clear trend of increasing median ΔTEWL%, starting from physicians with non-surgical specialisation (56 %) to medical surgeons (65 %), dentists (104 %), and dental surgeons (108 %), with the latter two groups showing particularly worrisome signs of work-related skin barrier impairment, since they had double the TEWL on hands than on forearms. Although less prominent, the same worsening trend was noted for skin pH, with dental surgeons having on average a 0.3 points higher skin pH on hands than on forearms. These findings were mainly associated with prolonged glove use and male sex. Our findings also suggest that comparing TEWL and pH between hands and forearms can better establish occupational skin barrier impairment on hands.

Mistakes in translation are mostly associated with toxic effects in the cell due to the production of functionally aberrant and misfolded proteins. However, under certain circumstances mistranslation can have beneficial effects and enable cells to preadapt to other stress conditions. Mistranslation may be caused by mistakes made by aminoacyl-tRNA synthetases, essential enzymes that link amino acids to cognate tRNAs. There is an strain expressing isoleucyl-tRNA synthetase mutant variant with inactivated editing domain which produces mistranslated proteomes where valine (Val) and norvaline (Nva) are misincorporated into proteins instead of isoleucine. We compared this strain with the wild-type to determine the effects of such mistranslation on bacterial growth in oxidative stress conditions. When the cells were pre-incubated with 0.75 mmol/L Nva or 1.5 mmol/L Val or Nva and exposed to hydrogen peroxide, no beneficial effect of mistranslation was observed. However, when the editing-deficient strain was cultivated in medium supplemented with 0.75 mmol/L Val up to the early or mid-exponential phase of growth and then exposed to oxidative stress, it slightly outgrew the wild-type grown in the same conditions. Our results therefore show a modest adaptive effect of isoleucine mistranslation on bacterial growth in oxidative stress, but only in specific conditions. This points to a delicate balance between deleterious and beneficial effects of mistranslation.

The invasion of Ukraine and military operations around Ukrainian nuclear power plants and other nuclear facilities have prompted us to search for radiocaesium in mosses from the Kopački Rit Nature Park in Croatia, since mosses are known bioindicators of airborne radioactive pollution, and Kopački Rit is a known low radiocaesium background area. Sampling was finished in August 2023, and our analysis found no elevated radiocaesium levels. Kopački Rit therefore remains a suitable place for future detection of anthropogenic radioactive pollutants.

The aim of this study was to explore occupational safety in pregnant Croatian healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. To this end we composed an anonymous questionnaire that included pregnancy data, risk assessment and mitigation, and workplace intervention and distributed it to HCWs through social media of their groups and associations. The study includes a total of 173 respondents (71.1 % physicians, 19.7 % nurses, 9.2 % other HCWs) diagnosed with pregnancy in 2020 and 2021. Employers were notified about HCWs' pregnancy at the eighth (IQR 7.0-11.0) week of pregnancy, which delayed workplace risk assessment and mitigation beyond the first trimester. Only 19.6 % of the participants had the risk assessed and mitigated, mostly on their own initiative (76.5 %). After notifying employers about pregnancy, 37.0 % of participants opted for temporary work incapacity (TWI) due to "pregnancy complications" despite healthy pregnancy, 16.8 % were granted a pregnant worker's paid leave at the expense of the employer, while 5.8 % continued to work at the same workplace. Nurses used the TWI benefit more frequently than physicians (58.8 % vs 30.1 %, P=0.004). Our findings suggest that occupational safety of pregnant HCWs in Croatia lacks clear-cut and transparent strategies to protect pregnant HCWs, forcing them to misuse the healthcare system.

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia ( Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.

Pedagogical work, especially with preschool children, is one of the most stressful professions, and the incidence of stress-related illnesses among preschool teachers is higher than in the general population. The aim of this cross-sectional study, conducted between October 2018 and April 2019, was to examine the prevalence of the burnout syndrome in a representative sample of 482 preschool teachers in Serbia and the factors associated with it. For this purpose, the participants completed a questionnaire composed of six sections: the socio-demographic and socio-economic characteristics, health and lifestyle characteristics, workplace and employment characteristics; Copenhagen Burnout Inventory (CBI); Beck Depression Inventory (BDI), and the Zung Self-Rating Anxiety Scale (SAS). The frequency of the total burnout was 27.1 %. The frequency of burnout on the CBI was 25.4 % for personal burnout, 27.0 % for work-related burnout, and 23.4 % for client-related burnout. Multivariate logistic regression analysis with total burnout as an outcome variable showed that being single (OR: 0.18; 95 % CI: 0.05-0.58), having poor (OR: 6.05; 95 % CI: 1.05-34.91), or average (OR: 3.60; 95 % CI: 1.57-8.25) self-rated health, not having didactic/play tools (OR: 2.71; 95 % CI: 1.21-6.04), having a higher score on the BDI (OR: 1.19; 95 % CI: 1.09-1.29) or SAS (OR: 1.10; 95 % CI: 1.03-1.18) was significantly associated with the total burnout among our participants. Our study shows the worryingly high prevalence of the burnout syndrome among preschool teachers in Serbia and points to its association with mental health issues, depression, and anxiety.

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes () for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

Traditional medicine has used sage ( L.) preparations for centuries to prevent and treat various inflammatory and oxidative stress-induced conditions. The aim of this study was to determine the bioactive properties of a sage leave extract obtained with environmentally friendly aqueous extraction and lyophilisation in primary human peripheral blood cells. To that end we measured the total phenolic and flavonoid content (TPC and TFC, respectively) with gas chromatography-mass spectrometry (GC-MS). Non-cytotoxic concentrations determined with the trypan blue assay were used to assess the antioxidant (DPPH, ABTS, and PAB assay), antigenotoxic (CBMN assay), immunomodulatory (IL-1β and TNF-α), and neuroprotective effects (AChE inhibition). The extract contained high TPC (162 mg GAE/g of dry extract) and TFC (39.47 mg QE/g of dry extract) concentrations, while β-thujone content was unexpectedly low (below 0.9 %). Strong radical-scavenging activity combined with glutathione reductase activation led to a decrease in basal and HO-induced oxidative stress and DNA damage. A decrease in TNF-α and increase in IL-1β levels suggest complex immunomodulatory response that could contribute to antioxidant and, together with mild AChE inhibition, neuroprotective effects. Overall, this study has demonstrated that aqueous sage leave extract reduces the levels of thujone, 1,8-cineole, pinene, and terpene ketones that could be toxic in high concentrations, while maintaining high concentrations of biologically active protective compounds which have a potential to prevent and/or treat inflammatory and oxidative stress-related conditions.

Even at low levels, exposure to ionising radiation can lead to eye damage. However, the underlying molecular mechanisms are not yet fully understood. We aimed to address this gap with a comprehensive approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, and Metascape to identify six key regulator genes associated with radiation-induced eye damage (, , , , , and ), all of which have physical interactions. Some of the identified molecular functions revolve around DNA repair mechanisms, while others are involved in protein binding, enzymatic activities, metabolic processes, and post-translational protein modifications. The biological processes are mostly centred on response to DNA damage, the p53 signalling pathway in particular. We identified a significant role of several miRNAs, such as hsa-miR-183 and hsamiR-589, in the mechanisms behind ionising radiation-induced eye injuries. Our study offers a valuable method for gaining deeper insights into the adverse effects of radiation exposure.

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the , , and gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O ), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

Environmental pollution with plastic nanoparticles (PNPs) has rendered hazard assessment of unintentional human exposure to neurotherapeutic drugs through contaminated water and food ever more complicated. Due to their small size, PNPs can easily enter different cell types and cross different biological barriers, while their high surface-to-volume ratio enables higher adsorption of chemicals. This is how PNPs take the role of a Trojan horse as they enhance bioaccumulation of many different pollutants. One of the health concerns related to water pollution with neurotherapeutic drugs is endocrine disruption, already evidenced for the anticonvulsant drug carbamazepine (Cbz) and antidepressant fluoxetine (Flx). Our study aimed to evaluate endocrine disrupting effects of Cbz and Flx in mixtures with polystyrene nanoparticles (PSNPs) using the luciferase assay to measure oestrogen receptor activity in T47D-KBluc cells treated with Cbz-PSNPs or Flx-PSNPs mixtures and compare it with the activities observed in cells treated with individual mixture components (Cbz, Flx, or PSNPs). Dose ranges used in the study were 0.1-10 mg/L, 1-100 µmol/L, and 0.1-10 µmol/L for PSNPs, Cbz, and Flx, respectively. Our findings show that none of the individual components activate oestrogen receptors, while the mixtures induce oestrogen receptor activity starting with 0.1 mg/L for PSNPs, 10 µmol/L for Cbz, and 0.5 µmol/L for Flx. This is the first study to evidence that PSNPs increase oestrogen receptor activity induced by neurotherapeutic drugs at their environmentally relevant concentrations and calls for urgent inclusion of complex mixtures in health hazard assessments to inform regulatory response.

Healthcare workers handling antineoplastic drugs (ADs) in preparation units run the risk of occupational exposure to contaminated surfaces and associated mutagenic, teratogenic, and oncogenic effects of those drugs. To minimise this risk, automated compounding systems, mainly robots, have been replacing manual preparation of intravenous drugs for the last 20 years now, and their number is on the rise. To evaluate contamination risk and the quality of the working environment for healthcare workers preparing ADs, we applied the Failure Mode Effects and Criticality Analysis (FMECA) method to compare the acceptable risk level (ARL), based on the risk priority number (RPN) calculated from five identified failure modes, with the measured risk level (MRL). The model has shown higher risk of exposure with powdered ADs and containers not protected by external plastic shrink film, but we found no clear difference in contamination risk between manual and automated preparation. This approach could be useful to assess and prevent the risk of occupational exposure for healthcare workers coming from residual cytotoxic contamination both for current handling procedures and the newly designed ones. At the same time, contamination monitoring data can be used to keep track of the quality of working conditions by comparing the observed risk profiles with the proposed ARL. Our study has shown that automated preparation may have an upper hand in terms of safety but still leaves room for improvement, at least in our four hospitals.