Medication-overuse headache (MOH) associated with migraine is a biologically driven disorder involving central sensitization, maladaptive neuroplasticity, and enhanced calcitonin gene-related peptide (CGRP) signaling. While structured deprescribing addresses medication-related drivers, withdrawal alone often provides limited and unsustained benefit. Anti-CGRP preventive therapies offer targeted modulation of migraine pathways without reinforcing medication overuse. This study integrates pathophysiological insights with real-world evidence from a single-center study of 47 patients treated with combined deprescribing and anti-CGRP therapy. Clinically meaningful reductions in monthly migraine days were observed, with 85.1% achieving ≥50% reduction at 6 months and 78.7% achieving >75% reduction at 12 months. Our clinical experience also suggests that long-standing combination analgesic overuse may be associated with a slower treatment response. The present findings support a mechanism-based treatment approach and suggest that combining preventive therapy with deprescribing may optimize long-term outcomes in patients with migraine-associated MOH.

This study investigated the ability of pavement mushrooms (Agaricus bitorquis (Quél.) Sacc.) to uptake heavy metals (Cu, Zn, Pb, Cr, Cd, and Ni) from the soil in Sarajevo’s urban area and the potential health hazards related to their consumption. The levels of tested heavy metals in soil and mushroom samples were determined using the flame atomic absorption spectroscopy technique. The phytoextraction potential was estimated using bioaccumulation factor (BAF) analysis, while the evaluation of the non-carcinogenic, long-term risk to human health through the consumption of the studied mushrooms was performed using the Target Hazard Quotient (THQ) value. The study revealed that particular soils within the urban zone of Sarajevo are contaminated with Cu and Pb. The average content of tested heavy metals in the fruiting bodies of pavement mushrooms decreased in the order of Cu > Zn > Pb > Cr > Ni > Cd, regardless of the soils from which the mushrooms were collected. The BAF values obtained in this study indicated that pavement mushrooms have a high ability to accumulate Cd and Cu, while showing a limited ability to absorb Pb and Ni. The THQ values for all heavy metals analysed in pavement mushrooms were considerably lower than one for both adults and children, suggesting that consuming pavement mushrooms gathered from experimental sites poses no non-carcinogenic health risks related to the heavy metals studied.

Intra-tumour heterogeneity is a major obstacle to durable responses to targeted cancer therapy, yet how different resistant cell states interact within the same tumour remains poorly understood. In this study, we demonstrate cooperativity between co-occurring resistant states in a single tumour. Using BRAF mutant melanoma as a paradigm, we generate three different resistant states within a single model and demonstrate that they exhibit varying differentiation states and migratory capacities and share few common therapeutic vulnerabilities. Through a combination of experiments, including using Cre-mediated recombination to generate heterogeneity in existing tumours, and in silico modelling, we show that intra-tumour heterogeneity is the most favoured state for therapy resistant tumours. This is underpinned by signalling between different melanoma states, with YAP1 active cells providing supporting signals for other cells but inhibiting their own proliferation. Optimal disease control requires targeting both the YAP1 active cell state and the inter- cellular communication networks. We identify the histone demethylase inhibitor GSK-J4 as being particularly effective in targeting both features of resistant tumours and demonstrate its ability to control melanoma with multiple concurrent resistance mechanisms.

Airborne micro- and nanoplastics are emerging inhalation contaminants, yet their effects on the first human airway barrier, the nasal epithelium, remain poorly understood. Here, we investigated metabolic responses of normal human nasal epithelial cells exposed to polystyrene nanoplastics (100 nm), microplastics (7 μm), or their mixture using comprehensive metabolomics and lipidomics of both cells and secretome analyzed by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Nanoplastics induced the strongest intracellular perturbations, characterized by increased amino acid- and purine-related metabolites, including homocystine, uric acid, aspartic acid, and glutamic acid, together with marked depletion of membrane lipids, particularly phosphatidylcholines. The particle mixture produced partially overlapping but generally attenuated responses, whereas microplastics alone caused comparatively modest changes. This attenuation was consistent with particle characterization showing partial nanoplastic adsorption onto microplastics, which reduced the freely dispersed nanoplastic fraction in the mixture. Secretome profiling revealed distinct extracellular metabolic fingerprints, with nanoplastics and mixtures increasing metabolites linked to oxidative stress, amino acid turnover, and detoxification, while reducing several membrane-derived lipids. Pathway enrichment analysis highlighted disturbances in carbohydrate metabolism, glycerophospholipid metabolism, the pentose phosphate pathway, and amino acid and nucleotide metabolism. Overall, these findings identify normal human nasal epithelial cells as a metabolically sensitive target of plastic particle exposure and suggest that nanoplastics are primary drivers of the observed metabolic perturbations at the airway interface in vitro.

Exceeding global warming of 1.5 °C in the near term is now unavoidable. An overshoot pathway, in which exceedance is followed by decline to or below the threshold through net-negative emissions, is now the only remaining route back to 1.5 °C. Permanent exceedance forecloses the recovery from climate impacts that an overshoot pathway may permit, yet even an overshoot pathway leaves lasting legacies. To characterise the reversibility of temporary overshoot impacts, we propose a three-layer analytical framework distinguishing hazards (with four dimensions: magnitude, duration, rate of exceedance, and rate of decline), biophysical responses (reversible vs persistent change), and socioeconomic outcomes (reversible vs irreversible impact). We introduce the socioeconomic commitment threshold, endogenous to the overshoot trajectory: how much overshoot intensity a system can experience before the losses it accumulates persist after temperatures decline, explained by three mechanisms: non-substitutability, threshold-crossing, and lock-in. A typology linking biophysical persistence with socioeconomic irreversibility illustrates how reversible biophysical change can produce irreversible socioeconomic loss, while persistent biophysical change need not produce irreversible outcomes where adaptive capacity is sufficient. Whether temporary exceedance produces permanent harm is determined primarily by socioeconomic rather than biophysical factors, except where permanent biophysical change exceeds adaptation limits. For systems and communities with low adaptive capacity, overshoot concentrates irreversible legacies even where temperatures subsequently decline, placing equity and justice at the centre of overshoot assessment.

This text is a review of the book: Safet Bandžović, Rusija i Istočno pitanje: izazovi deosmanizacije i balkanski odgovori, I, II, Sarajevo: Institut za historiju Univerziteta u Sarajevu, 2026.

AIM To assess fatigue severity in patients with rheumatoid arthritis (RA) using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and to examine its association with demographic, socioeconomic, clinical, and lifestyle-related factors. METHODS This cross-sectional observational study included 90 adults with RA. Fatigue was assessed using the FACIT-F scale, and disease activity was assessed using the Disease Activity Score in 28 joints (DAS28). Continuous variables were summarised as medians and interquartile ranges (IQRs). Associations were evaluated using Spearman correlation, Mann-Whitney U, Kruskal-Wallis, and robust linear regression analyses. RESULTS The median FACIT-F score was 37.0 [IQR 27.0 - 45.0], and 35.6% of patients had moderate-to-severe fatigue. FACIT-F correlated negatively with DAS28 (ρ = -0.381; p < 0.001). In multivariable robust regression, DAS28 remained associated with FACIT-F score after adjustment for age and disease duration (β = -3.54; 95% confidence interval -5.39 to -1.68; p < 0.001), whereas age and disease duration were not significant. FACIT-F scores differed by sex and employment status but not by treatment category. CONCLUSION Fatigue is a prevalent and clinically important symptom in RA. Higher disease activity was associated with greater fatigue severity, supporting comprehensive assessment of fatigue beyond inflammatory disease activity alone.

AIM To compare outcomes of elective open inguinal hernia repair under local anaesthesia (LA) and general anaesthesia (GA). METHODS This retrospective cohort included 833 adults treated in Tuzla during 2017-2025. The primary outcome was any early adverse outcome within 30 days. Secondary outcomes included analgesic requirement, chronic groin pain, discomfort, dissatisfaction, and recurrence. Logistic regression adjusted for age, American Society of Anesthesiologists physical status, hernia characteristics, and technique. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported; Benjamini-Hochberg correction was applied to secondary outcomes. RESULTS The LA group included 425 patients and the GA group 408. Postoperative analgesia was required in 338 (79.5%) and 110 (27.0%) patients, respectively (p<0.001). An early adverse outcome occurred in 79 (18.6%) and 35 (8.6%) patients (aOR 2.08, 95% CI 1.31-3.30; p = 0.002), mainly because of more haematomas with LA, 54 (12.7%) versus 20 (4.9%) (p < 0.001). Chronic groin pain did not differ after adjustment (aOR 1.26, 95% CI 0.81-1.96; p = 0.310). Dissatisfaction was higher with LA, 85 (20.8%) versus 40 (10.1%) (aOR 1.95, 95% CI 1.27-2.99; p = 0.002). Eight recurrences were recorded. Median follow-up was 14 months (interquartile range 12-18 months). CONCLUSION LA was associated with more early adverse outcomes and dissatisfaction than GA. Chronic pain did not differ after adjustment, and recurrence was similar. Selection bias and residual confounding should be considered.

AIM To evaluate the prognostic value of the CHA2DS2-VASc score in relation to major adverse cardiovascular events (MACE) and cardiovascular mortality in patients with non-ST elevation myocardial infarction (NSTEMI), and to assess its association with clinical and echocardiographic characteristics. METHODS This prospective, observational, cohort study included 311 NSTEMI patients admitted to the Internal Medicine Clinic at the University Clinical Centre Tuzla between January 2023 and April 2024. The patients were stratified into intermediate-risk (score < 4) and high-risk (score ≥ 4) groups based on the CHA2DS2-VASc score at admission. Demographic, clinical, and echocardiographic data were collected, including electrocardiography (ECG) and transthoracic echocardiography. All patients were followed for 3 months (90 days) to assess the occurrence of MACE and cardiovascular mortality. RESULTS The patients in the high-risk group were older and had significantly lower left ventricular ejection fractions and larger left atrial diameters compared with the intermediate-risk group. During the 3-month follow-up, MACE occurred in 11.9% of high-risk and 3.9% of intermediate-risk patients; cardiovascular mortality was observed exclusively in the high-risk group (2.5%). A higher CHA2DS2-VASc score was significantly associated with cardiovascular mortality (p = 0.003), but not with overall MACE (p = 0.393). Moderate predictive accuracy for mortality (AUC = 0.64) and shorter event-free survival in the high-risk group (log-rank p = 0.005) were observed. CONCLUSION The CHA2DS2-VASc score showed potential as a simple and accessible tool for early identification of NSTEMI patients at risk of cardiovascular death. Its significant association with mortality supports its role as a supplementary risk stratification tool, although these findings require validation in larger, multicentre studies.

AIM The most common type of kidney transplantation in Bosnia and Herzegovina is from living donors, but there is a lack of published data on glomerular filtration rate (GFR) values and kidney outcomes in living kidney donors. This study aimed to evaluate the safety of living kidney donation at our centre. METHODS One hundred and seventy living kidney donors at the University Clinical Centre Tuzla were analysed. Initially, there were 170 participants; however, only 31 provided all the required medical data and completed the study. GFR was estimated (eGFR) using the CKD-EPI and MDRD formulas, and a web-based calculator was used to predict GFR > 90 ml/min/1.73 m², along with measurement of creatinine clearance (CrCl). Measured GFR (mGFR) was assessed through technetium-99m diethylene triamine pentaacetic acid (DTPA) renogram, with follow-up visits to estimate post-donation GFR. RESULTS The CKD-EPI, MDRD, and web-based application showed similar diagnostic performances, with MDRD and CKD-EPI systematically underestimating mGFR. CrCl demonstrated strong diagnostic performance. Follow-up visits showed that most donors had post-donation eGFR values between 45 and 89 mL/min/1.73 m², with none progressing to pre-dialysis or the dialysis stage after kidney donation. CONCLUSION CrCl demonstrated strong diagnostic performance in our study population, and the DTPA renogram reliably assessed kidney function. Post-donation eGFR levels were satisfactory, indicating that our diagnostic workup for potential living kidney donors in our centre is safe and effective.

AIM To determine whether immunohistochemical B7-H3 expression is associated with magnetic resonance imaging (MRI)-derived tumour volume, peritumoral brain oedema volume, and oedema index in adult gliomas. METHODS This retrospective radiopathological correlation study included 99 consecutive patients with histopathologically confirmed intracranial gliomas surgically treated between 2013 and 2021. B7-H3 expression (clone RBT-B7H3, Bio SB, USA) was evaluated using staining intensity, percentage of positive tumour cells, and a composite immunoreactive score (IRS). Tumour volume (TV), peritumoral brain oedema volume (PTBE), and oedema index (EI) were calculated from orthogonal MRI measurements. Spearman correlation and crude and adjusted linear regression were used. Adjusted models included age, sex, tumour grade, and Ki-67. RESULTS Median TV was 29.31 cm3 (IQR 12.17-49.12), median PTBE was 84.51 cm3 (IQR 47.59-178.18), and median EI was 4.56 (IQR 3.83-5.00). B7-H3 IRS correlated strongly with TV (r = 0.921, p < 0.001) and PTBE (r = 0.920, p < 0.001), but not with EI (r = -0.105, p = 0.299). After adjustment, B7-H3 IRS remained associated with ln(TV) (beta = 0.228, 95% CI 0.190-0.265, p < 0.001) and ln(PTBE) (beta = 0.178, 95% CI 0.152-0.204, p < 0.001), but not with EI (beta = 0.001, 95% CI -0.083 to 0.084, p = 0.990). CONCLUSION B7-H3 expression is independently associated with MRI-derived tumour volume and peritumoral brain oedema volume in adult gliomas, but not with oedema index, supporting its relationship with absolute MRI-visible lesion burden.

AIM To investigate the relationship between coronary artery calcium (CAC) score and left ventricular global longitudinal strain (LV GLS) in patients with arterial hypertension who had a negative treadmill exercise stress test but mild to intermediate coronary stenosis on coronary computed tomography angiography (CCTA). METHODS A total of 53 hypertensive patients (mean age 54.8 ± 4.8 years; 50.9% male) with 30-50% coronary stenosis on CCTA were included. Patients with diabetes, malignancy, or established coronary/peripheral artery disease were excluded. CAC score, left ventricular ejection fraction (LVEF, Simpson's method), and LV GLS (speckle-tracking echocardiography) were measured. Groups were stratified by GLS (< 18.5% vs. ≥ 18.5%) and LVEF (< 60% vs. ≥ 60%), and CAC score differences were assessed using the Mann-Whitney U test. RESULTS The median CAC score was 27 (IQR 16-44.5), median LVEF 60% (IQR 58-63%), and mean GLS 19.37 ± 0.89%. No overall association was found between CAC score and LV function by LVEF or GLS. In patients with left anterior descending (LAD) stenosis (30-50%), reduced LV function was linked to significantly higher CAC score. Median CAC score was higher in patients with GLS ≤ 18.5% (157 vs. 44.5; p = 0.019) and LVEF <60% (157 vs. 44.5; p = 0.019). No significant associations were found in right coronary artery (RCA), circumflex artery (Cx), or three-vessel stenosis subgroups. CONCLUSION Higher CAC score in hypertensive patients with mild LAD stenosis and negative stress testing identify those at risk of subclinical LV dysfunction.

AIM To identify factors associated with emergence agitation (EA) in adults undergoing abdominal surgery under general anaesthesia. METHODS This prospective two-centered study included 107 patients (≥18 years) who underwent abdominal surgery at two hospital centres between February 2025 and September 2025. Collected variables included demographics, American Society of Anesthesiologists (ASA) classification, education level, smoking and alcohol use, comorbidities, fasting status, urgency and type of surgery, and anaesthesia duration. Hemodynamic parameters were recorded before induction, before endotracheal intubation (ETI), and before extubation. EA was assessed using the Richmond Agitation-Sedation Scale (RASS) and the Sedation-Agitation Scale (SAS) before (T1) and 10 minutes after extubation (T2). RESULTS At T2, EA incidence was 22% (23 patients) according to SAS and 41% (44 patients) according to RASS. SAS-defined EA at T1 was associated with ASA status ≥ III (aOR 2.35, 95% CI 1.05-5.25; p = 0.028) and lower blood pressure before extubation (aOR 0.62, 95% CI 0.50-0.96; p = 0.016). SAS-defined EA at T2 was associated with higher body weight (aOR 1.20, 95% CI 1.03-1.40; p = 0.017) and higher heart rate before extubation (aOR 1.45, 95% CI 1.25-1.80; p = 0.022). According to RASS, lower blood pressure before induction was associated with EA at T1 (aOR 0.88, 95% CI 0.78-0.99; p = 0.045), while nasogastric tube presence was associated with EA at T2 (aOR 2.10, 95% CI 1.06-4.15; p = 0.034). CONCLUSION EA after general anaesthesia in adults undergoing abdominal surgery is common. Identification of associated factors may improve perioperative risk assessment and early recognition.

This paper examines the perceptions of citizens, university professors, and practitioners regarding the stigmatization and social acceptance of persons with mental health difficulties. The aim of the study was to investigate the presence of stereotypes, prejudice, social distance, and discrimination toward persons with mental health difficulties, as well as to identify factors contributing to their stigmatization and possibilities for destigmatization. The research was conducted using a mixed-methods approach. The quantitative component included a survey of 175 citizens from Sarajevo Canton and Tuzla Canton, while the qualitative component involved the analysis of responses to open-ended questions and 20 semi-structured interviews with university professors and social workers. The findings indicate that stereotypes, prejudice, and social distance toward persons with mental health difficulties are still present, although the majority of participants expressed willingness to accept and support these individuals. Education, media campaigns, direct contact with persons with mental health difficulties, and their greater participation in public life were identified as the most important mechanisms for reducing stigmatization. The contribution of this study lies in providing a better understanding of the complexity of stigmatization through the analysis of perceptions held by different social groups, while highlighting the need for the development of systemic and multisectoral activities aimed at destigmatization and the social inclusion of persons with mental health difficulties in Bosnia and Herzegovina.

AIM To assess whether serum interleukin-6 (IL-6) measured on postoperative day 14 reflects adhesion severity and to compare intraperitoneal alteplase, N-acetylcysteine (NAC), and combined treatment. METHODS In this exploratory randomised study, 40 male Wistar rats were allocated to untreated adhesion, alteplase, NAC, alteplase plus NAC, or sham groups (n = 8 per group). Serum IL-6 and macroscopic adhesion grade were assessed on day 14. Group differences were analysed using the Kruskal-Wallis tests followed by Benjamini-Hochberg-adjusted Dunn comparisons; associations were assessed using Spearman correlation. RESULTS Serum IL-6 differed among groups (H = 18.08; p = 0.001). Median serum IL-6 concentrations were 14.52 pg/mL (IQR 9.91-19.13) in untreated animals, 30.70 pg/mL (IQR 27.31-34.09) after alteplase (p = 0.003), 24.95 pg/mL (IQR 17.48-32.42) after NAC (p = 0.037), 30.76 pg/mL (IQR 24.16-37.36) after combined treatment (p = 0.007), and 18.36 pg/mL (IQR 11.49-25.23) in sham animals (p = 0.320). Adhesion grades differed (H = 20.80; p < 0.001) and were lower after alteplase and combined treatment (both p = 0.041); the NAC comparison was not significant (p = 0.054). Serum IL-6 was not correlated with adhesion grade (ρ = -0.131; 95% CI -0.425 to 0.189; p = 0.422). CONCLUSION A single serum IL-6 measurement on day 14 did not reflect adhesion severity. Serial serum measurements and concurrent peritoneal or tissue biomarkers may be more informative.