Ždralovac peatland in the karst field Livanjsko polje in southwestern Bosnia and Herzegovina with an area of about 3.500 ha has always been drained and used for the regional people. But drainage, agriculture and climate change cause the peat drying in the summer and create the conditions for frequent fires and serious changes of peat properties. Since 1.000 ha of peatland was used for agriculture (abandoned areas for 25 years that are being cultivated again today), and the extracted peat is used as a raw material for the plant growing substrate. The presence of certain pollutants is a good indicator of the suitability of peat for the plant production. In this paper, the state of peat related to contamination with heavy metals, polycyclic aromatic hydrocarbons - PAHs and pesticide residues was investigated in undrained peat areas, reclamation areas and peat burning sites. The presence of heavy metals in concentrations higher than permitted was not recorded. The presence of combustion products PAHs was recorded on all surfaces, but only naphthalene exceeds the permitted concentrations of organic pollutants. Only pesticide residue of dichlorodiphenyltrichloroethane (DDT) was recorded in abandoned meliorated areas used in agriculture, and the concentration exceeded the level of uncontaminated land.

Five neutral heteroleptic mononuclear vanadium(IV) hydrazone complexes ([VOL(bpy)]), derived from 2-hydroxy-5-methylacetophenone and various acid hydrazides (furoic, thiophene, benzoic, nicotinic, and isoniazid), were synthesized and shown to exhibit improved antidiabetic efficacy in streptozotocin-induced diabetic rats, with reduced toxicity and minimal bioaccumulation compared to maltolato- and picolinato-based vanadium species. Structural identity was established by spectroscopic methods. Crystal structures were obtained for four complexes, providing insight into their solid-state chemistry. Stability studies in simulated intestinal and gastric fluids showed that the complexes largely retained their integrity under intestinal conditions, whereas decomposition occurred in the highly acidic gastric environment within several minutes. In vivo experiments revealed a structure-antihyperglycemic activity relationship. The nicotinic-containing complex showed the highest activity, reducing blood glucose levels by 67% within 7 days of treatment, while the remaining complexes improved glycemic control by more than 50%. Bioaccumulation studies demonstrated <1.1% uptake in the liver and kidneys and negligible accumulation in the brain. The presented vanadium compounds enhance antidiabetic potential by addressing key limitations, particularly bioaccumulation and toxicity, associated with vanadium agents previously evaluated in clinical trials.

Digital twins (DTs) are increasingly used to monitor and secure Industrial Control Systems (ICS), yet detecting stealthy False Data Injection Attacks (FDIAs) that manipulate system states within normal physical bounds remains challenging. Deep learning anomaly detectors often over-generalize such subtle manipulations, while classical fault detection methods do not scale well in highly correlated multivariate systems. We propose a closed-loop Information-Theoretic Digital Twin (IT-DT) framework for real-time anomaly detection. N4SID identification is combined with steady-state Kalman filtering to quantify residual distribution shifts via closed-form KL divergence, capturing both mean deviations and malicious cross-covariance shifts. Evaluations on the SWaT and WADI datasets show that IT-DT achieves F1-scores of 0.832 and 0.615, respectively, with better precision than deep learning baselines such as TranAD. Computational profiling indicates that the analytical approach requires minimal memory and provides approximately a 600x inference speedup over transformer-based methods on CPU hardware. This makes the framework suitable for resource-constrained industrial edge controllers without GPU acceleration.

Diabetes mellitus is a growing global health challenge, and digital health technologies offer new opportunities to support self-management. Mobile applications can benefit both patients and healthcare professionals; however, awareness and integration of these tools into community pharmacy practice remain limited. As accessible frontline providers, pharmacists are well positioned to promote digital health, yet their readiness and engagement require further investigation. A cross-sectional survey was conducted among community pharmacists in Serbia using a structured questionnaire. Developed through a consensus-based process, the instrument assessed pharmacists’ awareness, attitudes, and experiences with digital health technologies, focusing on mobile applications for diabetes self-management. Only 15.8% of pharmacists were aware of such applications, and 2.4% reported receiving relevant training. Higher digital health technology literacy was associated with greater awareness, confidence, and preference for digital learning. Most participants supported expanding pharmacists’ roles in advising patients on digital tools and expressed interest in structured education and official guidance. These findings indicate limited awareness and training in mobile health applications among community pharmacists. Enhancing digital competencies through targeted education and structured guidance may facilitate greater integration of digital tools into routine pharmacy practice and strengthen pharmacists’ roles in chronic disease management.

OBJECTIVE This study aimed to investigate which of the two vitamin K antagonists, warfarin or acenocoumarol, provides more stable anticoagulation control in patients with mechanical heart valves and atrial fibrillation. PATIENTS AND METHODS This was a prospective, one-year clinical cohort study. In total, 73 outpatients with mechanical heart valves and atrial fibrillation who were already treated with warfarin or acenocoumarol were recruited from the Blood Transfusion Institute of the Federation of Bosnia and Herzegovina. The prothrombin time target values, expressed as the international normalized ratio (INR), were 2.0-3.0/4.0. Numerical data between the treatment groups were summarized descriptively. RESULTS Patients in the warfarin (N=35) and acenocoumarol (N=38) treatment groups were similar in terms of sex, age, body mass index, body surface area, and number of concomitant drugs known to interact with vitamin K antagonists. The number of INR measurements per patient, number of INR measurements within the therapeutic range per patient, mean time interval between successive INR measurements, and mean INR values across consecutive measurements were similar in both groups. However, compared to acenocoumarol, warfarin treatment seemed to be associated with more stable anticoagulation, i.e., with a higher mean time in the therapeutic range (TTR) (76.1±24.2 vs. 69.1±21.5%) and a smaller proportion of patients below all predefined TTR thresholds (<60%, <65%, and <70%). CONCLUSION Our unadjusted descriptive results suggested that warfarin, compared to acenocoumarol, may provide more stable and therefore safer anticoagulation control in patients with mechanical heart valves and atrial fibrillation. To confirm this, larger prospective clinical studies are needed in patients with mechanical heart valves with or without atrial fibrillation.

Background and Objectives: Mitogen-activated protein kinases (p38, JNK, ERK1/2) regulate key cellular processes essential for kidney development. Disruptions in these signaling pathways can lead to congenital anomalies of the kidney and urinary tract (CAKUT), a major cause of pediatric kidney disease. This study investigates and compares the expression of these molecules in normal fetal kidneys and CAKUT-affected tissues. Materials and Methods: Forty-three human fetal kidney samples, including controls and specimens with horseshoe, hypoplastic, and dysplastic kidneys, were analyzed across developmental phases 2–4 using immunofluorescence. Quantitative image analysis and statistical comparisons were performed between developmental stages and phenotypes. Results: ERK1/2 expression increased during late development in control kidneys but was significantly reduced in hypoplastic kidneys. p38 showed phase-dependent alterations, with early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys. JNK exhibited significant phase-dependent upregulation in horseshoe kidneys. P38 displayed dynamic expression associated with nephron maturation. Conclusions: MAPK pathways show distinct developmental and phenotype-specific expression patterns in human fetal kidneys. These differences reflect divergent pathogenic mechanisms in CAKUT and may support improved molecular characterization of congenital renal anomalies.

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of pediatric chronic kidney disease, yet the molecular mechanisms underlying these malformations remain incompletely understood. While genetic studies have identified numerous CAKUT-associated genes, conventional knockout approaches often result in embryonic lethality or fail to reveal tissue-specific gene functions. This review aims to synthesize findings from conditional knockout mouse studies that have elucidated the spatiotemporal requirements of key signaling pathways during kidney development. Methods: We conducted a narrative synthesis of studies employing Cre-loxP conditional gene targeting in mouse models, identified through systematic searches of PubMed and cross-referencing of key primary research. Studies were selected based on their use of lineage-specific Cre drivers (Six2-Cre, Hoxb7-Cre, Foxd1-Cre) to investigate nephron progenitor maintenance, ureteric bud branching morphogenesis, and stromal–epithelial interactions. Results: Conditional knockout studies have redefined CAKUT pathogenesis as a disorder of dose-dependent signaling, temporal regulation, and inter-compartmental communication. WNT/β-catenin signaling operates in a biphasic, dose-dependent manner in nephron progenitors, with Six2-Cre-mediated β-catenin deletion causing premature progenitor depletion. BMP and FGF pathways demonstrate dose-dependent and context-specific functions in progenitor maintenance, while GDNF/RET signaling is essential for ureteric bud outgrowth and branching. Importantly, stromal-specific deletions have uncovered non-cell-autonomous mechanisms regulating nephron formation. Haploinsufficiency studies demonstrate that partial pathway disruption can reduce nephron endowment without overt CAKUT, predisposing to adult-onset hypertension and chronic kidney disease. Conclusions: Conditional gene targeting has mechanistically redefined CAKUT from a collection of structural malformations to a spectrum of disorders arising from quantitative perturbations in lineage-specific signaling networks. These findings establish that phenotypic severity is determined by the degree of pathway disruption, the developmental timing of insult, and the compartment affected, providing a framework for interpreting oligogenic interactions and variable penetrance in human CAKUTs.

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8+ T cells and regulatory FOXP3+ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3+ T lymphocyte density and lower CD8+/FOXP3+ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3+ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3+ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC.

Background Appropriate oral hygiene practices established in early childhood are essential for preventing dental caries. Parental awareness and supervision during the early school years play a key role in the development of effective daily oral hygiene habits. However, data on oral hygiene practices and the use of preventive dental products among children at school entry remain limited in many primary healthcare settings. Materials and methods This cross-sectional study included 307 six-year-old children who attended routine school-entry dental examinations at the Department of Dentistry, Public Health Institution "Health Center" Živinice, Bosnia and Herzegovina, between September 2022 and September 2024. Parents completed a structured questionnaire on the timing of the child’s first dental visit, initiation of toothbrushing, caregiver involvement in daily oral hygiene, and use of mechanical and chemical oral hygiene products. Categorical variables were summarized using descriptive statistics, and differences in questionnaire responses were analyzed using the Pearson Chi-square (χ²) test, with a significance level of p < 0.05. Results Delayed initiation of the first dental visit and toothbrushing were commonly reported. Only a minority of children attended their first dental visit following eruption of the first tooth, while most began brushing after eruption of several primary teeth. Parental supervision of oral hygiene was inconsistent, and independent brushing from the beginning was reported in a subset of children. Although regular toothbrush and toothpaste use was nearly universal, the use of adjunctive preventive products was limited, and more than half of parents were unaware of the fluoride content of their children's toothpaste. Conclusion Oral hygiene practices among six-year-old children appear suboptimal, with delayed initiation of preventive care and limited parental awareness of fluoride use. Educational interventions aimed at improving caregiver knowledge and supervision of children’s oral hygiene practices may support the development of more effective preventive behaviors at school entry.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, eosinophilia, and multisystem involvement. Renal manifestations are relatively uncommon but may be severe and rapidly progressive, and fatal hemorrhage from arteriovenous fistulas (AVFs) represents an uncommon yet catastrophic complication in patients with advanced kidney disease. We report a case of a 70-year-old man with long-standing asthma, chronic rhinosinusitis with nasal polyposis, marked eosinophilia, and progressive renal failure. After years of fragmented clinical manifestations, a clinical diagnosis of EGPA was considered based on clinical, laboratory, and immunological findings, supported by fulfillment of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria in the absence of histopathological confirmation, in the setting of rapidly progressive renal dysfunction. Induction immunosuppressive therapy with high-dose corticosteroids and cyclophosphamide was initiated. Due to advanced chronic kidney disease and the anticipated need for renal replacement therapy, a left radiocephalic AVF was constructed. Seventeen days later, the patient experienced spontaneous fistula rupture at home, resulting in massive hemorrhage, refractory hemorrhagic shock, and death. This case illustrates the consequences of delayed EGPA diagnosis and highlights the possibility of fatal vascular access complications in the setting of active systemic vasculitis, underscoring the importance of careful timing of invasive procedures, heightened clinical vigilance, and structured patient education when planning vascular access in patients with active inflammatory disease.

Introduction: Traditional diagnostics rely on microscopy, dipstick tests, and the gold‑standard urine culture, which is reliable but time‑consuming. Flow cytometry for urinary analysis offers a fast, objective, and highly automated approach that can improve the selection of samples for culture and accelerate clinical decision‑making. Flow cytometry uses fluorescent and scatter detection to quantify cells, bacteria, and other particles in urine, processing thousands of events per sample and generating parameters that correlate with the presence of infection. Methods: This retrospective study included 200 hospitalized adult patients (>18 years) admitted to the Clinic for Infectious Diseases, University Clinical Center Tuzla in Tuzla, Bosnia and Herzegovina. A urinary tract infection (UTI) was diagnosed based on standardized clinical and laboratory criteria. Urine samples were analyzed using the Sysmex UF‑4000 flow cytometer, and diagnostic thresholds for leukocyte and bacterial counts were determined by receiver operating characteristic (ROC) analysis and Youden’s Index. Results: Among 200 hospitalized patients, females predominated (124 vs. 76). Optimal cut-offs were ≥120/µL for leukocytes (area under the curve (AUC) 0.88, sensitivity 91.2%, specificity 75.3%) and ≥1367/µL for bacteria (AUC 0.95, sensitivity 90.3%, specificity 90.7%). Sex-specific analyses showed higher accuracy in males, with cut-offs of ≥1012/µL for bacteria (AUC 0.97) and ≥122/µL for leukocytes (AUC 0.94), while in females, the best thresholds were ≥1797/µL for bacteria (AUC 0.94) and ≥113/µL for leukocytes (AUC 0.84). The empirically developed UTI risk score (0-2) further improved stratification: Score 0 strongly predicted negative cultures (NPV >97%), while Score 2 was highly associated with positive cultures (PPV >94%). Conclusions: Automated urine flow cytometry offers a fast and accurate screening tool for UTIs, with bacterial counts outperforming leukocytes in diagnostic reliability. Sex-specific cut-offs and the UTI risk score enhance clinical applicability by improving stratification and reducing unnecessary cultures. While findings support integration of flow cytometry into routine practice, the single-center design, hospitalized cohort, and exclusion of pregnant women and children limit broader generalization, warranting validation in larger, multicenter studies.