Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. Methods: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking P. aeruginosa growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. Results: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. Conclusions: The evolution of colistin resistance in P. aeruginosa appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of P. aeruginosa colistin resistance, warranting further investigation in clinical isolates.

This manuscript reports the synthesis and characterization of 19 novel heterostilbene carbamates, designed as selective butyrylcholinesterase (BChE) inhibitors with potential applications in the treatment of neurodegenerative disorders, particularly Alzheimer’s disease. The compounds were synthesized from resveratrol analogs, and their structures were confirmed by NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction for selected derivatives (compounds 1 and 4). In vitro assays demonstrated high selectivity toward BChE over acetylcholinesterase (AChE), with compound 16 exhibiting exceptional inhibitory activity (IC50 = 26.5 nM). Furthermore, compound 16 showed moderate anti-inflammatory effects by inhibiting LPS-stimulated TNF-α production in peripheral blood mononuclear cells. In silico ADME(T) profiling revealed favorable pharmacokinetic properties and low mutagenic potential for the majority of compounds. Molecular docking and molecular dynamics simulations confirmed stable binding interactions within the BChE active site. These results highlight heterostilbene carbamates as promising lead structures for developing novel therapeutic agents targeting neurodegenerative diseases.

To address the issue of groundwater vulnerability management and analysis, an algorithm was developed based on which the necessary research was conducted in the broader area surrounding the water source Novoselija used for water supply of the population in the city of Banja Luka (Republic of Srpska, Bosnia and Herzegovina). Within the GIS, as one of the spatial data techniques, the GOD method for vulnerability assessment was used. Data visualization within the GIS program package, combined with the aforementioned GOD method, enabled a clearer understanding of the spatial distribution of groundwater vulnerability in this area, which made it possible to delineate different zones: from negligible to extreme vulnerability. The high degree of the parameter has been determined in the zone of the actual water source and is associated with terrace and gravels sediments. In the alluvial sediment zone, located south of the water source, vulnerability has been assessed as extreme. In this area, there is certainly a potential risk of groundwater vulnerability to all pollutants, with a very rapid impact in most contamination scenarios. From the east and the west side, the aquifer in question is confined by flysch deposits of Cretaceous age, which are hydrogeologically characterized as conditionally “waterless” parts of the terrain, and within them, the vulnerability has been classified as negligible. The results of this research are also important for later delineation of the sanitary protection zone of the aquifer in question.

Abstract Intraepithelial lymphocytosis is a hallmark of microscopic colitis commonly presenting with debilitating chronic watery diarrhea. The exact pathophysiology remains unclear but is believed to involve an abnormal immune response to the luminal microenvironment in genetically predisposed individuals. Medications like nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and antidepressants, as well as alcohol consumption and smoking have been regarded as risk factors for microscopic colitis. Lymphocytic colitis often responds well to anti-inflammatory treatment, with budesonide being a first line therapy. Relapse is common after discontinuing budesonide, often necessitating low-dose maintenance therapy. Advanced therapies including anti-TNF-alpha (e.g. infliximab) or anti-integrin (e.g. vedolizumab) agents as well as JAK inhibitors (e.g. upadacitinib) may be considered in refractory cases. However, confirmation of the diagnosis and ruling out other etiologies are necessary before intensifying treatment. Here, we present the case of a 78-year-old female patient with a twenty month history of chronic refractory diarrhea, repeatedly diagnosed as microscopic lymphocytic colitis. Following further deterioration and the development of hepatosplenomegaly with atypical liver lesions, a review of colonic biopsies and additional work-up led to the correct diagnosis.

Linguistic errors remain a persistent challenge for B2-level EFL learners, with research showing that grammatical misapplication accounts for nearly half of the language inaccuracies. This study investigates 942 errors in argumentative essays written by Bosnian EFL learners, focusing on grammatical, lexical, and typographical challenges that impact their English writing proficiency. The data, consisting of 90 essays with a total word count of 45,786, were collected and analyzed following a structured procedure: collection, identification, description, and evaluation of learners’ errors. A descriptive-qualitative error analysis approach was employed to classify errors and examine their underlying causes systematically. To ensure reliability and consistency in the analysis, three instructors independently reviewed the essays. Inter-rater reliability was achieved through collaborative discussions, where any discrepancies in error classification were resolved through consensus. Errors were categorized into grammatical (50.2%), word-choice (29.3%), and typographical (20.5%) types and further analyzed to determine their origins as intralingual or interlingual. A deeper investigation revealed that 58% of errors were intralingual, resulting from overgeneralization and rule misapplication, while the remaining 42% were interlingual, influenced by Bosnian language interference. These findings highlight the need for focused interventions, particularly in grammar and vocabulary instruction. By uncovering error patterns and their causes, the study contributes to refining pedagogical strategies that support EFL learners’ writing proficiency.

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making.

Despite significant advances in knowledge and the development of guidelines, the management of hypoplastic left heart syndrome (HLHS) remains highly variable. A structured questionnaire was circulated across European Association of Paediatric & Congenital Cardiology (AEPC) affiliated centres. The aims were to evaluate standards in pre-operative assessment, types of surgery, follow-up and medical practices in children with HLHS. Thirty-one centres from 20 countries completed the survey. Delivery of babies with HLHS occurred in co-located maternity hospitals in 74% of centres; 29% were planned for spontaneous onset of labour, while 54% decided on a case-by-case basis. The preferred initial palliation was a right ventricle-pulmonary artery conduit in 55% of cases, modified Blalock-Thomas Taussig shunt (mBTTS) in 35%, and hybrid in 15% of cases. Timing for Glenn varied from 3 to 6 months of age and preoperative examination varied greatly: 65% performed cardiac catheterization and only 19% performed cardiac magnetic resonance. Stage III palliation was performed at a highly variable interval (2—6 years of age), nearly always employing an extracardiac conduit. Fenestration was routinely performed in 61% and reserved for borderline cases in 39%. All the centers adopted warfarin for the first 3–12 months after Fontan completion, and continued if a fenestration was present, while in non-fenestrated aspirin was left by most centers (e.g. 68%). However, there was a high disparity in the use of heart failure medications (e.g. in interstage I-II 35% use ACE-inhibitors, and only 26% digoxin). Follow-up practice also varied widely with only 60% employing specific protocols. Conclusion: This first multi-centre European survey from 31 centres from 20 different European countries highlighted a high practice variation in HLHS management across all the stages of Single Ventricle (Fontan) palliation. Major variations pertained to pre- and post-surgical investigations, surgical strategy for stage I and III, medical treatment regimens, and follow-up programs. What is Known: • Hypoplastic left heart syndrome (HLHS) remains one of the most complex and challenging congenital cardiac defects to manage. • Investigating the management of children with HLHS across different European centres can facilitate study of the most effective management strategies. What is New: • Significant variation in HLHS management were reported in relation to pre- and post-surgical examinations, surgical strategy at stage I and III, medical treatment regimens, and follow-up programs. • Greater standardisation of imaging and diagnostic evaluation, medical treatment and follow-up surveillance may improve outcomes for these vulnerable patients and warrants further study. What is Known: • Hypoplastic left heart syndrome (HLHS) remains one of the most complex and challenging congenital cardiac defects to manage. • Investigating the management of children with HLHS across different European centres can facilitate study of the most effective management strategies. What is New: • Significant variation in HLHS management were reported in relation to pre- and post-surgical examinations, surgical strategy at stage I and III, medical treatment regimens, and follow-up programs. • Greater standardisation of imaging and diagnostic evaluation, medical treatment and follow-up surveillance may improve outcomes for these vulnerable patients and warrants further study.

This research investigates the efficiency of two methods for extracting bioactive compounds from fig leaves (Ficus carica) using different solvents. Dried fig leaves were used as  extraction material. The focus is on Soxhlet extraction and Ultrasound-assisted extraction (UAE) methods. Also, two different solvents, methanol and ethanol, were used for extractions. Given that the enzyme ficin is one of the significant bioactive compounds in fig leaf latex, the aim was to explore and determine which method and solvent gives a higher extraction yield and better preservation of thermolabile components such as this enzyme. The results show that Soxhlet extraction provides a higher total extract yield and requires a longer extraction time. In this study, the highest yields of 12.3% were obtained using the methanol solvent using the Soxhlet method compared to ultrasonic extraction which showed a lower yield of 6.4%. In contrast to that, ultrasound-assisted extraction (UAE) yields a higher-quality extract in a shorter extraction time. However, due to the high temperatures required for Soxhlet extraction, denaturation of ficin occurs, which leads to the formation of a dry extract without the presence of this enzyme. Ultrasound-assisted extraction (UAE) method does not require high temperatures, which enables the preservation of ficin and the formation of a mucilaginous extract due to the presence of enzymes. Due to the temperature sensitivity of bioactive compounds, the choice of extraction method significantly affects the stability and quality of the final extract.

Agency, pertaining to planning and executing actions, is a core feature of the political landscape. Our study examines the temporal dynamics of agentic language in political online discourse during the 2020 U.S. Congressional Elections, spanning 180 days before and after Election Day, and before the Capitol Hill riots. We coded 495,252 messages posted by Democratic and Republican candidates on Twitter for agentic language, which was more prevalent in tweets of politicians who won elections. Temporal analyses revealed increased agency as critical political events approached, whether a planned democratic event (Election Day) or a sudden disruptive protest (Capitol riots). The study enhances our understanding of the role of agency expression in political social media communication. Politicians may strive to evoke agency among voters to encourage political engagement, and voters may be cautioned by our results about this subtle (possibly unaware) manipulative strategy.

This study explores Sn‐doped CsPbBr3 perovskites as advanced semiconductor materials for radiation detectors. Using density functional theory, we reveal tunable band gaps from 2.803 eV (undoped) to 1.139 eV ( Sn), enabling broad‐spectrum detection from visible light to gamma rays. Optical analysis highlights high absorption coefficients in the 4‐ to 6‐eV range and enhanced visible‐light absorption, ensuring efficient photon‐to‐electron conversion. Anisotropic dielectric properties, with increasing refractive indices and dielectric constants, improve directional sensitivity and photon capture. Phonon analysis confirms dynamic stability, ensuring robustness under operational stresses and high radiation flux. The substitution of Sn for Pb reduces toxicity, offering an eco‐friendly alternative for sustainable detector technologies. These findings establish Sn‐doped CsPbBr3 as a versatile material for ‐ray spectroscopy, X‐ray imaging, and directional photodetectors, combining tunable optoelectronic properties, structural stability, and environmental sustainability to advance next‐generation radiation detection applications.

Being physically active is probably one of the most important decisions that any person can make in order to improve their own health, regardless of gender or age. For the student population, regular physical exercise is of great importance due to excessive learning and sitting. The aim of this research was to show how many students are playing sports in their leisure time, through a survey conducted on a sample of undergraduate students from the Džemal Bijedić University in Mostar. From total number of 142 participants, 76.8% of them are playing sports (63.4% recreational and 13.4% competitive), and most of them are playing team sports with the ball (23.9%) or doing sports activities in the gym (31.7%). 95.8% of students think that sports have positive impact on students life quality, which is less from the percentage of students who play sports (76.8%), so we can conclude that despite the knowledge of importance of physical activity, students don't behave regarding to what they think about sport and physical activity.

Effects of hydro-and aromatherapy on rehabilitation of patients with myocardial infarction (MI) have not yet been sufficiently investigated. This pilot study explores the anti-inflammatory effects of a combined hydro-and aromatherapy protocol in MI patients targeting inflammation. A prospective study included 22 post-MI patients undergoing 28 days of hydro-and aromatherapy at the Institute "Dr Simo Milosevic" in Montenegro. Biochemical assessments, including complete blood count and cytokine analysis, were conducted before and after treatment. Following therapy, patients exhibited increased leukocytes neutrophils, and platelets, and reduced monocytes. Fibrinogen levels significantly increased, aligning with the expected post-MI healing process. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations significantly decreased. The therapy also led to a drop in nitric oxide (NO), cortisol, dopamine, and Beclin-1 levels, highlighting potential cardiovascular benefits. These findings encourage further research with larger cohorts and extended follow-up to elucidate the long-term benefits of this protocol.

The paper focuses on the role of artificial intelligence in tourism