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The chemical composition of Pulicaria dysenterica(L.) Bernh. aerial parts essential oil (EO), growing wildin Bosnia and Herzegovina, was presented in the study. In addition to the EO composition, antimicrobial and cytotoxic activities were also tested. The aerial parts of P. dysentericacontained 0.3% of yellow, liquid, fragrant EO. The 51 components identified accounted for 81.09% of the oil. The EO was characterized by the presence of a high concentration of oxygenated sesquiterpenes 51.83% while oxygenated monoterpenes constituted 15.57%, sesquiterpene hydrocarbons 9.32% and non-terpene compounds presented 4.37% of the EO. The dominant compounds were the sesquiterpenes caryophyllene oxide, (E)-nerolidol, β-caryophyllene and monoterpene nerol. The antimicrobial activity of EO was tested against selected ATCC strains of microorganisms, the bacteria Staphylococcus aureus, Pseudomonas aeruginosaand Escherichia coli, and the fungus Candida albicans. The results showed that the investigated EO inhibited the growth of all selected ATCC strains of microorganisms. The best result was obtained against Escherichia colibacteria with MIC value of 1 mgmL-1. The cytotoxicity of EO was measured against the HeLa cell line using the MTT method with IC50of 188.52 μgmL-1.This study has provided scientific baseline data on the therapeutic properties of P. dysenterica. KEYWORDS:Pulicaria dysenterica, essential oil,antimicrobial activity,citotoxicity

I. Ianache, A. Skrzat-Klapaczyńska, D. Jilich, L. Fleischhans, I. Gmizić, J. Ranin, Antonios Papadopoulos, K. Protopapas et al.

BACKGROUND The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. METHODS A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. RESULTS Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH.Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. CONCLUSIONS Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.

Jelena Ostojić, D. Kozić, Milana Panjković, Biljana Georgievski-Brkic, Dusan Dragicevic, A. Lovrenski, J. Boban

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the “NAA-like peak”, was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.

Jessy Le Du-Carrée, C. K. Palacios, A. Rotander, M. Larsson, Andi Alijagic, O. Kotlyar, Magnus Engwall, V. Sjöberg et al.

Tire wear particles (TWP) stand out as a major contributor to microplastic pollution, yet their environmental impact remains inadequately understood. This study delves into the cocktail effects of TWP leachates, employing molecular, cellular, and organismal assessments on diverse biological models. Extracted in artificial seawater and analyzed for metals and organic compounds, TWP leachates revealed the presence of polyaromatic hydrocarbons and 4-tert-octylphenol. Exposure to TWP leachates (1.5 to 1000 mg peq L-1) inhibited algae growth and induced zebrafish embryotoxicity, pigment alterations, and behavioral changes. Cell painting uncovered pro-apoptotic changes, while mechanism-specific gene-reporter assays highlighted endocrine-disrupting potential, particularly antiandrogenic effects. Although heavy metals like zinc have been suggested as major players in TWP leachate toxicity, this study emphasizes water-leachable organic compounds as the primary causative agents of observed acute toxicity. The findings underscore the need to reduce TWP pollution in aquatic systems and enhance regulations governing highly toxic tire additives.

Milena Mlakić, Danijela Barić, A. Ratković, Ivana Šagud, Ivona Čipor, Ivo Piantanida, I. Odak, I. Škorić

Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles 23–34, as well as 1,2,3-triazolium salts 44–51, were synthesized and tested. Triazolium salts 44–46 showed excellent activity while salts 47 and 49 showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules 24–27. The representative of newly prepared compounds, 45 and 50, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases’ active sites identified cation–π interactions as the most responsible for the stability of the enzyme–ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed.

S. Shahcheraghi, M. Alimardani, Malihe Lotfi, Marzieh Lotfi, V. Uversky, S. T. Guetchueng, Sushesh Shrivastsa Palakurthi, Nitin B. Charbe et al.

Armin Šljivo, Nemanja Lukić, Aladin Altic, Slobodan Tomić, A. Abdulkhaliq, Leopold Reiter, D. Bota, Eljakim Mahendran et al.

Background and Objectives. In emergency departments, chest pain is a common concern, highlighting the critical importance of distinguishing between acute coronary syndrome and other potential causes. Our research aimed to introduce and implement the HEAR score, specifically, in remote emergency outposts in Bosnia and Herzegovina. Materials and Methods. This follow-up study conducted a retrospective analysis of a prospective cohort consisting of patients who were admitted to the remote emergency medicine outposts in Canton Sarajevo and Zenica from 1 November to 31 December 2023. Results. This study comprised 103 (12.9%) patients with low-risk HEAR scores and 338 (83.8%) with high-risk HEAR scores, primarily female (221, 56.9%), with a mean age of 63.5 ± 11.2). Patients with low-risk HEAR scores were significantly younger (50.5 ± 15.6 vs. 65.9 ± 12.1), had fewer smokers (p < 0.05), and exhibited a lower incidence of cardiovascular risk factors compared to those with high-risk HEAR scores. Low-risk HEAR score for prediction of AMI had a sensitivity of 97.1% (95% CI 89.9–99.6%); specificity of 27.3% (95% CI 22.8–32.1%); PPV of 19.82% (95% CI 18.67–21.03%), and NPV of 98.08% (95% CI 92.80–99.51%). Within 30 days of the admission to the emergency department outpost, out of all 441 patients, 100 (22.7%) were diagnosed with MACE, with AMI 69 (15.6%), 3 deaths (0.7%), 6 (1.4%) had a CABG, and 22 (4.9%) underwent PCI. A low-risk HEAR score had a sensitivity of 97.0% (95% CI 91.7–99.4%) and specificity of 27.3% (95% CI 22.8–32.1%); PPV of 25.5% (95% CI 25.59–28.37%); NPV of 97.14% (95% CI 91.68–99.06%) for 30-day MACE. Conclusions. In conclusion, the outcomes of this study align with existing research, underscoring the effectiveness of the HEAR score in risk stratification for patients with chest pain. In practical terms, the implementation of the HEAR score in clinical decision-making processes holds significant promise.

H. Bečulić, Emir Begagić, Amina Džidić-Krivić, Ragib Pugonja, Namira Softić, Binasa Bašić, Simon Balogun, Adem Nuhović et al.

Introduction Clinicians encounter challenges in promptly diagnosing thoracolumbar injuries (TLIs) and fractures (VFs), motivating the exploration of Artificial Intelligence (AI) and Machine Learning (ML) and Deep Learning (DL) technologies to enhance diagnostic capabilities. Despite varying evidence, the noteworthy transformative potential of AI in healthcare, leveraging insights from daily healthcare data, persists. Research question This review investigates the utilization of ML and DL in TLIs causing VFs. Materials and methods Employing Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, a systematic review was conducted in PubMed and Scopus databases, identifying 793 studies. Seventeen were included in the systematic review, and 11 in the meta-analysis. Variables considered encompassed publication years, geographical location, study design, total participants (14,524), gender distribution, ML or DL methods, specific pathology, diagnostic modality, test analysis variables, validation details, and key study conclusions. Meta-analysis assessed specificity, sensitivity, and conducted hierarchical summary receiver operating characteristic curve (HSROC) analysis. Results Predominantly conducted in China (29.41%), the studies involved 14,524 participants. In the analysis, 11.76% (N = 2) focused on ML, while 88.24% (N = 15) were dedicated to deep DL. Meta-analysis revealed a sensitivity of 0.91 (95% CI = 0.86–0.95), consistent specificity of 0.90 (95% CI = 0.86–0.93), with a false positive rate of 0.097 (95% CI = 0.068–0.137). Conclusion The study underscores consistent specificity and sensitivity estimates, affirming the diagnostic test's robustness. However, the broader context of ML applications in TLIs emphasizes the critical need for standardization in methodologies to enhance clinical utility.

Maryam Golzardi, Altijana Hromić-Jahjefendić, Jasmin Šutković, O. Aydın, P. Ünal-Aydın, Tea Bećirević, E. Redwan, Alberto Rubio-Casillas et al.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50–70% are hospitalised. It has also been shown that 10–12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC. Conclusions: Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed.

M. Karataş, K. Parsova, Muhammed Keskin, Lutfi Ocal, Selami Doğan, Nurşen Keleş

BACKGROUND We aimed to investigate the prognostic value of serum albumin-to-creatinine ratio (sACR) in carotid artery stenting (CAS) patients regarding in-hospital and 5-year outcomes. METHODS This is a retrospective study. Baseline characteristics were compared between patients by admission albumin to creatinine ratio and categorized accordingly: T1, T2 and T3. 609 patients were included in the study. Serum albumin and creatinine levels at hospital admission were used to calculate the sACR. The primary endpoint was all-cause mortality. MACE consisted of stroke, transient ischemic attack (TIA), myocardial infarction (MI) and death. All follow-up data were obtained from electronic medical records or by interview. The study was terminated after 60 months of follow-up. RESULTS Serum albumin levels were found to be significantly lower in T1, while creatinine was found to be significantly higher in T1. T1 has the lowest sACR while T3 has the highest. In hospital, ipsilateral stroke, major stroke, MI and death were significantly higher in T1. In long-term outcomes, ipsilateral stroke, major stroke, and death were significantly higher in T1. CONCLUSIONS Low sACR values at hospital admission was independently associated with in-hospital and long-term mortality and major stroke in patients underwent CAS.

G. Temaj, S. Chichiarelli, Pelin Telkoparan-Akillilar, Sarmistha Saha, Nexhibe Nuhii, R. Hadziselimovic, Luciano Saso

It is known that more than 10% of genetic diseases are caused by a mutation in protein-coding mRNA (premature termination codon; PTC). mRNAs with an early stop codon are degraded by the cellular surveillance process known as nonsense-mediated mRNA decay (NMD), which prevents the synthesis of C-terminally truncated proteins. Up-frameshift-1 (UPF1) has been reported to be involved in the downregulation of various cancers, and low expression of UPF1 was shown to correlate with poor prognosis. It is known that UPF1 is a master regulator of nonsense-mediated mRNA decay (NMD). UPF1 may also function as an E3 ligase and degrade target proteins without using mRNA decay mechanisms. Increasing evidence indicates that UPF1 could serve as a good biomarker for cancer diagnosis and treatment for future therapeutic applications. Long non-coding RNAs (lncRNAs) have the ability to bind different proteins and regulate gene expression; this role in cancer cells has already been identified by different studies. This article provides an overview of the aberrant expression of UPF1, its functional properties, and molecular processes during cancer for clinical applications in cancer. We also discussed the interactions of lncRNA with UPF1 for cell growth during tumorigenesis.

Jasmina Marušić, E. Hasković, Anhel Koluh, Darko Tomić, Amer Ovčina, Ajdina Karic, Vedran Đido

Beakground: The prevalence of cardiovascular diseases in COVID-19 patients, such as hypertension, diabetes mellitus, and chronic obstructive pulmonary disease, which are the most common comorbid conditions in COVID-19 patients, is considered a risk factor for premature mortality in the population. The aim of the study is to compare the standard biochemical and hematological markers of COVID-19 patients on mechanical ventilation and those who have recovered, and to identify differences by gender and comorbidities, as well as the dominant marker in comorbidities that frequently shows statistical significance, in order to investigate its prognostic value in further research. METHODS The study is a retrospective study of patients with RT-PCR confirmed presence of the Sars-CoV-2 virus who were hospitalized at the Zenica Cantonal Hospital. The study lasted from February to April 2021. RESULTS The results of the study, which included a sample of 302 participants, indicate that men were more represented in both the mechanical ventilation group and the recovered group, with 59.6% compared to women with 40.4%. Among the investigated biochemical and hematological parameters, there was a significantly higher number of leukocytes, urea, creatinine, LDH, and troponin in patients on mechanical ventilation, while the number of platelets was significantly higher in recovered patients. The most common comorbidity was hypertension in both groups of patients, with 24.5%. In patients on mechanical ventilation with cardiovascular disease, there was a significantly higher number of leukocytes, urea, creatinine, LDH, and troponin. In the same patients with three comorbidities, there was a significantly higher number of leukocytes, troponin, and LDH, while recovered patients without comorbidities had a significantly higher number of platelets. CONCLUSIONS The male gender and comorbidities remain a vicious circle in COVID-19 infection, while biochemical and hematological markers can help in forecasting and improve the clinical treatment of these high-risk patients.

Marijana Srećković, Dušan Backović, T. Dugandžija, Igor Dragičević, Ljubica Pajić Nikolić, Maida Mulić, Bojan Damnjanović

SUMMARY The municipality of Bogatić, part of Mačva District, belongs to the Pannonian Basin, where high concentrations of arsenic in artesian wells were detected. Numerous epidemiological studies have confirmed the association of exposure to arsenic in drinking water and bladder cancer (C67). This retrospective ten-year analysis included age-standardized incidence rates (ASRs) and age-specific incidence rates of C67 in the municipality of Bogatić and rural municipalities of Mačva District. The concentration of arsenic in drinking water was determined at Šabac Public Health Institute (PHI) laboratories in 2015. ASRs were estimated using data from regional cancer registries at Šabac PHI and compared by use of the Mann-Whitney U test. Control population was recruited from an area where there were no artesian wells or hydrogeological conditions that would indicate elevated concentrations of arsenic in drinking water. Arsenic levels in all artesian wells in Bogatić municipality were 1.4 to 41 times higher than the maximum permissible concentration (mean 120 µg/L±165). Female subjects from Bogatić municipality had higher ASRs of C67 compared with the populations in rural municipalities of Mačva District (p<0.01), while the incidence of bladder cancer was by 13% greater than that in central Serbia (standardized incidence ratio, 113; 95% CI 96.97-131.35). Male subjects from Bogatić municipality had higher ASRs of C67 but the difference was not statistically significant (p>0.05). Our analyses suggested that exposure to arsenic in drinking water could triple the risk of bladder cancer. These results support the conclusions of previous studies that there may be an association between higher concentrations of arsenic in drinking water and higher ASRs of bladder cancer in both male and female subjects.

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