Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) overdose is one of the most important causes of drug-induced liver injury worldwide. Hepatotoxicity induced by APAP is mainly caused by the production of N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive intermediate formed predominantly via the cytochrome P450 2E1. Here, we used human studies and in vitro models to demonstrate that NAPQI-derived thiomethyl metabolites identified using high-resolution mass spectrometry could serve to monitor NAPQI detoxification and elimination in patients (after intake at recommended dose or after intoxication), and to study inter-individual variability in NAPQI production. Using in vitro human models, we showed that these thiomethyl metabolites are directly linked to NAPQI detoxification since they are mainly formed after exposure to glutathione-derived conjugates via an overlooked pathway called the thiomethyl shunt. These long-term thiomethyl metabolites have great potential in future clinical studies in order to provide a more reliable history of APAP ingestion in case of acute intoxication or to study underlying causes involved in APAP-induced hepatotoxicity. One Sentence Summary Thiomethyl metabolites are new markers to monitor the elimination of the toxic N-acetyl-p-benzoquinone imine after therapeutic use or intoxication.

Vine-leaved kitaibelia (Kitaibela vitifolia Willd.), also known as balkanmalva or chalice flower, is a critically endangered plant species with a high risk of extinction in the wild. A reason given for this is, among others, a low germination rate primarily caused by dormancy. The present study evaluated the seed germination and seedling growth parameters of vine-leaved kitaibelia in response to eight different pre-sowing treatments. The final germination percentage ranged from 0 % to 55 %, depending on the pre-sowing treatment. The most effective method for breaking dormancy and increasing vine-leaved kitaibelia seed germination was the treatment with seeds soaked in H2SO4 for 5 min. The mechanical scarification of vine-leaved kitaibelia seeds also improved germination as compared to control treatment, while treatments with nitric acid and gibberellic acid were not effective in enhancing seed germination. All evaluated seedling growth parameters were not affected by pre-sowing treatments. Considering that successful germination and seedling establishment are crucial for the regeneration of vine-leaved kitaibelia further studies are required in order to identify other pre-sowing treatments that could further enhance seed germination and, consequently, seedling development.

Goal: Artificial intelligence applied to medical image analysis has been extensively used to develop non-invasive diagnostic and prognostic signatures. However, these imaging biomarkers should be largely validated on multi-center datasets to prove their robustness before they can be introduced into clinical practice. The main challenge is represented by the great and unavoidable image variability which is usually addressed using different pre-processing techniques including spatial, intensity and feature normalization. The purpose of this study is to systematically summarize normalization methods and to evaluate their correlation with the radiomics model performances through meta-analyses. This review is carried out according to the PRISMA statement: 4777 papers were collected, but only 74 were included. Two meta-analyses were carried out according to two clinical aims: characterization and prediction of response. Findings of this review demonstrated that there are some commonly used normalization approaches, but not a commonly agreed pipeline that can allow to improve performance and to bridge the gap between bench and bedside.

Cigarette smoking (CS) and low physical activity levels (PAL) are known to be risk factors for cardiovascular diseases. However, few studies have examined the associations between these factors in population of university students, and, to the best of our knowledge, no study examined this issue in period after the COVID-19 pandemic, despite the detrimental social and health consequences of the pandemic. The aim of this cross-sectional study was to examine associations between sport-participation, PAL and CS among university-level students in the first year after the COVID-19 pandemic. Participants were 761 students (411 females) from three universities in Bosnia and Herzegovina and Croatia, who were tested using semi-structured anonymous questionnaires at the beginning of the 2022/2023 academic year. Questions included queries on sociodemographic characteristics, CS, PAL, and sport-participation. Differences between genders were established by Chi-square test and gender-stratified logistic regressions were calculated to evaluate the associations between sport-participation and PAL, with binomized CS (smoking vs. non-smoking). One third of participants were daily smokers. Logistic regression showed no correlation between PAL and smoking prevalence for total sample (OR = 0.88, 95%CI: 0.75-1.05), males (OR = 0.95, 95%CI: 0.41-1.45), or females (OR = 0.90, 95%CI: 0.54-1.52). In addition, sport participation was not significantly associated with smoking. Results did not prove that sport and physical exercising are a way of reducing the likelihood of smoking; this finding could be a characteristic of the studied sample of participants, but could also be related to the period that was observed (the first year after the COVID-19 pandemic). Further studies examining the associations between PAL/sport participation and other types of substance misuse are warranted.

Naphtho-triazoles and thienobenzo-triazoles have so far proven to be very potent inhibitors of the enzyme butyrylcholinesterase (BChE). Based on these results, in this work, new thienobenzo-thiazoles were designed and synthesized, and their potential inhibitory activity was tested and compared with their analogs, naphtho-oxazoles. The synthesis was carried out by photochemical cyclization of thieno-thiazolostilbenes obtained in the first reaction step. Several thienobenzo-thiazoles and naphtho-oxazoles have shown significant potential as BChE inhibitors, together with the phenolic thiazolostilbene being the most active of all tested compounds. These results are significant as BChE has been attracting growing attention due to its positive role in the treatment of Alzheimer’s disease. Computational examination based on the DFT approach enabled the characterization of the geometry and electronic structure of the studied molecules. Furthermore, the molecular docking study, accompanied by additional optimization of complexes ligand-active site, offered insight into the structure and stabilizing interactions in the complexes of studied molecules and BChE.

The influence of the ageing temperature on the hardness, electrical conductivity, thermal diffusivity and thermal conductivity of the EN AW-7075 aluminium alloy was studied in this paper. After solution treating the alloy at 480 °C for 1 h and quenching it in ice water, the investigated alloy was characterized using Differential Thermal Analysis (DTA) in order to determine the optimal temperatures for the isochronal ageing treatments. Afterwards, isochronal ageing was conducted at the temperature range of 110 °C-250 °C for 30 min The hardness, electrical conductivity, thermal diffusivity, thermal conductivity and microstructural features were investigated during the ageing treatments. Hardness had a peak value after ageing at 150 °C, while other properties gradually increased with the ageing temperature. Microstructural investigation of the aged alloy by SEM-EDS revealed the existence of precipitated phases that appear homogenously distributed in the microstructure.

At the end of 2018, Gazi Husrev-bey library in Sarajevo and the renowned institution for historical research in the Republic of Turkey, Türk Tarih Kurumu, signed a protocol on cooperation on the project of preparing and publishing the regesta of the voluminous manuscript Tārīẖ-i Enveri, History of Muhamed Enveri Kadić. For the next four years, both of these institutions, which kept the first copies of the History, undertook a series of activities in order to realize the signed project. On January 13, 2023, the Gazi Husrev-bey library marked its 486th anniversary by promoting the planned and completed part of the work. The fact that the name and work of this special archivist, copyist, poet, epigrapher and bibliophile was known in detail by a limited number of people outside the fields of Orientalism, Ottoman studies and history, imposes the need to present, in a concise form, his character, work and visions.

In our study, we investigated the chemical composition and cytotoxic activity of essential oils isolated from Dalmatian sage (Salvia officinalis L.) collected along the Adriatic coast of Croatia. Scanning electron microscopy (SEM) was used to examine the morphology of the stem and leaf surfaces. Essential oil excretory glands were detected on both the leaves and stem surfaces. The essential oils were isolated by hydrodistillation, and their chemical composition was determined by gas chromatography and mass spectrometry (GC-MS). Sage essential oils were mixtures of terpene compounds, among which the most common were: α- and β-thujone, camphor, and 1,8-cineol. Cytotoxic activity was tested using MTS assay on multiple cell lines: normal and immortalized fibroblasts (HF77FA and HDF-Tert), immortalized lung line (BEAS-2B), and breast adenocarcinoma (MDA-MB-231). The growth of treated cells was determined relative to control conditions without treatment. The immortalized lung line was the least resistant to the activity of the essential oils, whereas immortalized fibroblasts were the most resistant. Statistical analysis has connected the cytotoxic effect and chemical composition of the studied essential oils. To the best of our knowledge, this work is the first testing of the cytotoxic activity of S. officinalis EO’s on the BEAS-2B, HF77FA, and HDF-Tert cell lines. The presented data on essential oil chemical composition and cytotoxic effect on 4 types of human cells supports pharmacotherapeutic potential this plant is known to have.

Background: Thiomersal is used as a preservative of some vaccines or as a trace from the pathogen inactivation process in vaccine production. Prophylactic use of paracetamol upon vaccination is still common, even though paracetamol decreases immune response on some vaccines. Considering the cytotoxic and genotoxic potential of thiomersal and paracetamol and possible interaction in vivo, in vitro study was performed. Methods: The genotoxic and cytotoxic effects of thiomersal and paracetamol combination were examined on human lymphocyte cultures by using two methods: analysis of chromosomal aberrations and cytokinesis-block micronucleus cytome assay. Blood samples of three healthy donors were analyzed with the following concentrations of tested substances: thiomersal 1 µg/ml and 0.5 µg/ml, paracetamol 20 µg/ml, thiomersal 0.5 µg/ml with paracetamol 20 µg/ml and thiomersal 1.0 µg/ml with paracetamol 20 µg/ml. Results: The analysis of structural chromosomal aberrations was significantly increased in all treated cultures. In cells treated with the combination of thiomersal 1 µg/ml and 20 µg/ml of paracetamol, the number of aberrations was significantly decreased. Cytokinesis-block micronucleus cytome assay analyses showed significantly increased micronucleus frequency in lymphocytes cultivated with thiomersal 1 µg/ml compared to lymphocytes cultures exposed to thiomersal 0.5 µg/ml. Conclusions: Induction of structural chromosome aberrations and micronucleus is shown as a sign of genotoxicity for the examined concentrations of thiomersal and paracetamol. The suppressing effect of paracetamol on thiomersal genotoxicity in lymphocytes culture treated with thiomersal was shown to be indicative of further examination of paracetamol use in the prevention of genotoxicity.

The inflammatory injury of the mucous membranes lining the digestive tract, from the mouth to the anus, is called mucositis. One of the intriguing and compelling new therapeutic modalities that has emerged in recent decades due to advances in our understanding of this condition’s pathophysiology is probiotics. The purpose of this meta-analysis is to evaluate the efficiency of probiotics in the treatment of chemotherapy-induced mucositis for head and neck malignancies; a literature search was performed on PubMed, Lilacs, and Web of Science, and articles published from 2000 to 31 January 2023 were considered, according to the keywords entered. The term “Probiotics” was combined with “oral mucositis” using the Boolean connector AND; at the end of the research, 189 studies were identified from the search on the three engines. Only three were used to draw up the present systematic study and metanalysis; this meta-analysis showed that the treatment of mucositis with probiotics is an effective method, and the analysis of the results of these studies showed that the use of probiotics promoted a decrease in the severity of mucositis symptoms.

Glycans are an essential structural component of Immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation). We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Up- and downregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.

Regular exercise improves health, modulating the immune system and impacting inflammatory status. Immunoglobulin G (IgG) N-glycosylation reflects changes in inflammatory status; thus, we investigated the impact of regular exercise on overall inflammatory status by monitoring IgG N-glycosylation in a previously inactive, middle-aged, overweight and obese population (50.30 ± 9.23 years, BMI 30.57 ± 4.81). Study participants (N = 397) underwent one of three different exercise programs lasting three months with blood samples collected at baseline and at the end of intervention. After chromatographically profiling IgG N-glycans, linear mixed models with age and sex adjustment were used to investigate exercise effects on IgG glycosylation. Exercise intervention induced significant changes in IgG N-glycome composition. We observed an increase in agalactosylated, monogalctosylated, asialylated and core-fucosylated N-glycans (padj = 1.00 × 10−4, 2.41 × 10−25, 1.51 × 10−21 and 3.38 × 10−30, respectively) and a decrease in digalactosylated, mono- and di-sialylated N-glycans (padj = 4.93 × 10−12, 7.61 × 10−9 and 1.09 × 10−28, respectively). We also observed a significant increase in GP9 (glycan structure FA2[3]G1, β = 0.126, padj = 2.05 × 10−16), previously reported to have a protective cardiovascular role in women, highlighting the importance of regular exercise for cardiovascular health. Other alterations in IgG N-glycosylation reflect an increased pro-inflammatory IgG potential, expected in a previously inactive and overweight population, where metabolic remodeling is in the early stages due to exercise introduction.

Catalytic materials are the greatest challenge for the commercial application of water electrolysis (WEs) and fuel cells (FCs) as clean energy technologies. There is a need to find an alternative to expensive and unavailable platinum group metal (PGM) catalysts. This study aimed to reduce the cost of PGM materials by replacing Ru with RuO2 and lowering the amount of RuO2 by adding abundant and multifunctional ZnO. A ZnO@RuO2 composite in a 10:1 molar ratio was synthesized by microwave processing of a precipitate as a green, low-cost, and fast method, and then annealed at 300°C and 600°C to improve the catalytic properties. The physicochemical properties of the ZnO@RuO2 composites were investigated by X-ray powder diffraction (XRD), Raman and Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), UV-Vis diffuse reflectance spectroscopy (DRS), and photoluminescence (PL) spectroscopy. The electrochemical activity of the samples was investigated by linear sweep voltammetry in acidic and alkaline electrolytes. We observed good bifunctional catalytic activity of the ZnO@RuO2 composites toward HER and OER in both electrolytes. The improved bifunctional catalytic activity of the ZnO@RuO2 composite by annealing was discussed and attributed to the reduced number of bulk oxygen vacancies and the increased number of established heterojunctions.

BACKGROUND: Critical care medicine is a young branch of medicine, of which the development was much faster in High Income Countries (HICs) than in Low Resources Settings (LRS). Slovenia, as one of the successor states of former Yugoslavia, passed the process of transition and joined the European Union successfully. On the contrary, Bosnia and Herzegovina (B&H) went through the extremely difficult process of transition (four years of civil war), which left a deep scar to the healthcare system, including critical care medicine. OBJECTIVE: To examine the impact of HICs on the development of critical care in LRS. METHOD: This review examined the process of growing up the first modern Medical Intensive Care Unit (MICU) in the Republic of Srpska. RESULTS: The five-year process of transferring critical care knowledge from Slovenia to the health care system of Republic of Srpska has contributed to the existence of modern and state of the art MICU with tremendous social effects. CONCLUSION: The model of using the impact of HICs for improving critical care in LRS can be extrapolated to other similar settings.