Introduction: Ibrutinib has made significant contributions to the treatment of chronic lymphocytic leukemia (CLL) with recognized cardiovascular toxicities in some patients. This study aimed to assess the incidence of cardiotoxicity in CLL patients treated with ibrutinib and identify associated risk factors.Methods: This retrospective cohort study analyzed 79 CLL patients treated with ibrutinib at the University Clinical Center of Serbia. Patient characteristics, treatment outcomes, and cardiovascular events were analyzed to determine the incidence of cardiotoxicity and its potential predictors.Results: The median age at diagnosis was 58 years, with 63.3% male patients. Pre-existing cardiovascular conditions were present in 55.7% of patients. Cardiotoxicity occurred in 29.1% of patients, with atrial fibrilation developing in 10.1% patients (37.5% grade 3), leading to therapy discontinuation in 62.5% of those affected. Also, we diagnosed hypertension in 15.2%, heart failure in 7.6%, and myocardial infarction in 2.5% of patients. Furthermore, one case (1.3%) of sudden cardiac death was recorded. The administration of ibrutinib was ceased in 9 patients due to cardiotoxic effects. Patients with prior cardiovascular disease had a threefold increased risk of developing cardiotoxicity (HR=2.850; p=0.031). A history of hypertension was significantly associated withthe worsening of hypertension during ibrutinib therapy (HR=7.935; p=0.009). No significant associations were found between cardiotoxicity and other factors such as age, sex, number of prior treatment lines, clinical stage, or cytogenetic abnormalities.Discussion: This study underscores the importance of cardiovascular monitoring in CLL patients undergoing ibrutinib therapy, particularly those with pre-existing cardiovascular conditions. These findings highlight the need for individualized treatment planning and close follow-up to mitigate the risk of cardiotoxicity and optimize patient outcomes.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = −0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient’s level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

Background: The Health in All Policies (HiAP) approach promotes the systematic integration of health considerations into policymaking across non-health sectors to address social determinants of health and improve population health outcomes. Although increasingly recognized internationally, the extent of its legislative implementation in the Republic of Srpska remains unclear. Objective: To assess the extent to which HiAP principles are embedded in sectoral legislation in the Republic of Srpska and to identify strengths and gaps in current legal frameworks. Methods: A structured content analysis of the text of laws was conducted across ten priority sectors. Twenty-two laws were reviewed using an analytical framework based on five core HiAP components: health outcomes, intersectoral governance, health equity, evidence-informed policymaking, and monitoring and accountability. The presence and distribution of these components were systematically examined across sectors. Results: Health considerations were frequently reflected in the text of the analysed legislation. Explicit references to health outcomes and intersectoral governance were identified in more than 60% of laws. However, integration was uneven across sectors. Health equity principles were inconsistently incorporated, while monitoring, evaluation, and accountability mechanisms were insufficiently developed, with explicit provisions found in fewer than half of the laws. No analysed law formally mandated Health Impact Assessment as a policy instrument. Conclusions: The Republic of Srpska has an existing legislative basis for advancing HiAP, but implementation remains fragmented rather than systematic. Addressing identified gaps—particularly in health equity, Health Impact Assessment, and health-oriented monitoring mechanisms—through targeted legislative reforms could improve policy coherence, accountability, and long-term sustainability. To our knowledge, this is the first systematic content analysis of HiAP integration in the sectoral legislation of the Republic of Srpska; it applies a replicable analytical framework derived from the WHO HiAP Framework for Country Action that is transferable to other decentralised and transitional governance settings.

This paper discusses about colorectal cancer in correlation with certain genes. Based on the etiological factors, colorectal cancer can be stratified into familial, hereditary, and sporadic. Explorations into hereditary syndromes such as familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma have unveiled genomic alterations in APC, KRAS, and TP53 genes, which are also implicated in the pathogenesis of sporadic carcinoma. Colorectal cancer constitutes a malignant epithelial neoplasm and ranks among the most prevalent malignancies afflicting both sexes. Despite a persistently elevated mortality rate, the incidence of this carcinoma has exhibited a declining trend over the past decade, though it still represents a substantial public health concern. Advancements in research methodologies have led to the identification of rarer syndromes and their associated genes. Investigation of APC, KRAS, and TP53 genes contributory to the genesis of rare syndromes, in conjunction with previously documented genetic instances, has unveiled the mechanistic underpinnings of carcinogenesis. This has facilitated the development of more precise therapeutic modalities. Despite the notable plethora of newly discovered genetic alterations across various genes, it is imperative to persist in research endeavors to comprehensively elucidate the nature and significance of colorectal carcinoma development processes.

Two structurally tunable (propyl-3-ol)triphenyltin(IV) (Ph₃SnL₁) and (butyl-4-ol)triphenyltin(IV) (Ph₃SnL₂) compounds were investigated at the human serum transferrin (Tf) molecular interface to resolve how ligand architecture and protein metallation modulate organotin(IV) biocompound stability and lobe-selective binding. Steady-state fluorescence spectroscopy revealed efficient quenching of native Tf emission (λ_ex = 280 nm, 296–310 K, pH 7.4) without significant spectral displacement, indicating the predominant formation of non-fluorescent ground-state complexes. Calculated bimolecular quenching constants (K_q ~10¹² M⁻¹ s⁻¹) exceeded the diffusion-controlled aqueous limit, ruling out a collisional dynamic quenching mechanism and confirming static complexation as the principal origin of fluorescence suppression. Double-log binding analysis revealed moderate affinity (K_a ~10²–10³ M⁻¹) and an approximately single dominant binding event per protein (n ≈ 0.65–0.90). Temperature-dependent van’t Hoff evaluation yielded positive ΔH° and ΔS° values, supporting a spontaneous, entropy-favored association process largely governed by hydrophobic and dispersion-type contributions, consistent with lipophilic organotin(IV) scaffold accommodation. Iron (Fe³⁺) loading of Tf markedly enhanced ligand engagement, especially for Ph₃SnL₁, evidencing that metallation-induced lobe closure reshapes pocket accessibility and local polarity relevant for organotin(IV) binding presentation rather than simply strengthening empirical docking scores. Molecular docking localized the most stable Ph₃SnL₂ poses in the sterically confined, rigid C-lobe, while Ph₃SnL₁ preferentially penetrated the more adaptive N-lobe. ONIOM QM/MM refinement of docking poses confirmed strong interfacial stabilization (ΔE_int ≈ –38 to –62 kcal mol⁻¹) and clarified charge–packing interplay without invoking frontier orbital analysis. The results map multiscale structure–interaction relationships defining lobe preference and complex stability at the transferrin interface.

Health in All Policies (HiAP) seeks to integrate health considerations across sectors to improve population health and equity. This study examines how HiAP has been operationalised through legal instruments in Serbia, assessing the extent to which legislation incorporates health outcomes, intersectoral governance, equity, use of evidence, and mechanisms for monitoring and evaluation. Using an analytical framework inspired by the WHO 2014 HiAP framework, 10 sectors with potential health impacts were prioritised, and 21 key laws were reviewed. Data were extracted directly from legal texts and analysed against five core criteria. Findings indicate that HiAP is conceptually recognised in Serbian legislation but practical integration is fragmented. Health outcomes are most visible in sectors traditionally linked to health, such as education and traffic safety, whereas opportunities to promote health outside these sectors remain underutilised. Intersectoral collaboration is rarely formalised, equity for vulnerable populations—including those experiencing mental health challenges, gender inequities, migration, or language barriers—is limited, and evidence‐informed monitoring and evaluation are inconsistently applied. The study highlights the potential of legislation to support HiAP when combined with formalised intersectoral collaboration, clear health objectives, and mechanisms for evidence‐informed decision‐making. Moving forward, systemic reform is needed, including expanding the scope to ‘Health in/for All Policies and Legislation/Regulation’, embedding mental health and other priority areas into legal frameworks, promoting stakeholder co‐creation, and institutionalising monitoring. Such measures, adapted to diverse political and cultural contexts, can strengthen cross‐sectoral integration, standardise policy implementation, and embed health equity across governance domains.