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Z. Maksimović, S. Babić, Glorija Milanović, M. Rifatbegović

Leptospirosis, a reemerging zoonotic disease caused by pathogenic bacteria of the genus Leptospira, affects a wide range of domestic and wild animals. The only investigation into sheep leptospirosis in Bosnia and Herzegovina was conducted nearly 50 years ago. This study aimed to assess the seroprevalence of leptospirosis and to identify the most common serovars in sheep in Bosnia and Herzegovina, using the microscopic agglutination test (MAT). Leptospirosis seroprevalence was determined to be 2.16% at a cut-off titer of ≥1:100 (55/2542) and 8.10% at a cut-off of ≥1:25 (206/2542), with all positive cases related to a single serovar. The MAT titers were 1:25 and 1:100, with the majority of positive animals having low titer (1:25) (151/206; 73.3%). At a cut-off of ≥1:100, the sera most frequently reacted to Pomona (54.55%) and Hardjo (27.27%), and less commonly to Saxkoebing and Icterohaemorrhagiae (0.2%) (P<0.05). Odds of seropositivity were higher for Pomona and Hardjo than for Saxkoebing and Icterohaemorrhagiae. The results of this study showed for the first time in Bosnia and Herzegovina, the presence of serovar Icterohaemorrhagiae in sheep, with Pomona and Hardjo as the dominant serovars. Although the seroprevalence is low, the potential zoonotic risk requires continuous monitoring and control strategies to prevent the spread of leptospirosis.

BACKGROUND Inflammation-driven mechanisms play a central role in adverse outcomes after non-ST-elevation myocardial infarction (NSTEMI), yet simple, widely available biomarkers for early risk stratification remain insufficiently defined. Hemogram-derived indices and iron-related inflammatory markers may provide complementary prognostic information. OBJECTIVE To evaluate the prognostic significance of the mean platelet volume-to-monocyte ratio (MMR) and serum ferritin in predicting major adverse cardiovascular events (MACE) in patients with NSTEMI, and to assess the association of angiotensin-converting enzyme (ACE) inhibitor therapy with clinical outcomes. METHODS This prospective cohort study included 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023. All patients received dual antiplatelet therapy and high-intensity statins. The baseline evaluation included a complete blood count, serum ferritin, and C-reactive protein. MMR was calculated as the ratio of mean platelet volume to absolute monocyte count. Patients were followed for 12 months for the occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, urgent revascularization, stroke, or hospitalization for heart failure. RESULTS During follow-up, 103 patients (60.6%) experienced MACE. Admission MMR (18.1 ± 11.7 vs 13.2 ± 5.5; P = 0.003) and ferritin levels (284 ± 396 vs 152 ± 109 µg/L; P = 0.001) were significantly higher in patients with events. In multivariable analysis, both MMR (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P = 0.008) and ferritin (OR 1.28 per 100 µg/L, 95% CI 1.10-1.55; P = 0.003) independently predicted MACE, while ACE inhibitor therapy was associated with a lower risk (OR 0.24, 95% CI 0.08-0.70; P = 0.01). The combined model demonstrated good discriminative performance (AUC 0.72; 95% CI 0.64-0.80). CONCLUSION AND RELEVANCE Elevated admission MMR and ferritin were independently associated with a higher 1-year risk of MACE in patients with NSTEMI. ACE inhibitor therapy was associated with improved outcomes, although causality cannot be inferred. These findings suggest that readily available inflammatory biomarkers may complement established clinical parameters for early risk stratification and support continued guideline-directed pharmacotherapy in NSTEMI.

Catherine Dunn Shiffman, Dina Sijamhodžić-Nadarević

This article examines the use of collaborative online international learning to support educator and educational leadership preparation. As part of a university partnership, the authors piloted virtual exchanges in 2021 and 2022 between university students in the United States (U.S.) and Bosnia and Herzegovina (B.H.). The pilot included 18 U.S. doctoral leadership students and 22 B.H. bachelor's, master's and doctoral students in religious pedagogy and theology. Qualitative case study methods were used to examine two COILs. The authors analyzed curricular and instructional materials, student reflections, faculty notes and correspondence and publicly available B.H. media accounts. Reported learning emphasized reflection focused on cultural attitudes, knowledge and skills; intercultural and interlinguistic awareness; intercultural team functioning and educational leadership, system and policy comparisons. Supports for and challenges to reported learning were structural, curricular and instructional in nature. Little research exists on the use of virtual exchange for educational leadership preparation. This study offers early lessons for using virtual technologies to incorporate an international and intercultural dimension into educational leadership preparation.

Ariel J. Lee, Hao Sheng, Arnau Marin-Llobet, Zheliang Wang, Jaeyong Lee, Ren Liu, Xinhe Zhang, Emma Hsiao et al.

Neural activity reorganizes profoundly after birth, transitioning from highly synchronous population events to sparse, decorrelated firing in the mature brain. Although inhibitory maturation and shifts in excitation-inhibition balance have been implicated in this process, how individual neurons implement the transition remains unclear because rapid brain growth has prevented long-term, same-neuron mapping. Here, we introduce growth-adaptive spring electronics that provide depth-wise compliance during tissue expansion, maintaining a stable electrode-tissue interface over weeks of neonatal development. We developed a vision-language model-assisted spike processing pipeline for the developing brain that probabilistically matches units across days using high-density waveform spatial footprints, despite developmental changes in the neonatal brain. Together, these innovations enable spike-resolved mapping of the same neurons in rat visual cortex and medial prefrontal cortex from postnatal day 10 to 45. Using population coupling to quantify each neuron’s coordination with local population activity, we show that developmental decorrelation is driven primarily by a distinct subset of neurons that progressively shifts from strong to weak coupling during postnatal weeks 3 to 5, whereas other neurons remain stably weakly or strongly coupled throughout development. These results resolve population-level desynchronization into identifiable neuron-specific trajectories. This framework enables direct tests in neurodevelopmental disorder models, including schizophrenia and autism, of whether altered maturation reflects global circuit imbalance or selective disruption and mistiming of specific developmental programs.

E. Sher, Amina Džidić-Krivić, Emma Pinjić, Nejra Selak, Kanita Omerbasic, A. Chupin, Andrej Belančić, Almir Fajkić

Chimeric Antigen Receptors (CAR) T-cell therapy is a ground-breaking discovery in immunotherapy, mainly known for its exceptional results in treating haematological malignancies. The latest research has revealed that the potential of CAR T-cell therapy extends far beyond its current capabilities and could represent a novel therapeutic approach for treating various cancers. This review aims to summarize the latest innovations in CAR T-cell therapy applied in cancer treatment, including multiple myeloma, osteosarcoma, glioblastoma, melanoma and various childhood malignancies. However, several challenges limit success of CAR T-cell therapy, including the antigen escape phenomenon, 'on-target off-tumour' toxicity, penetration into solid tumour tissue, alongside the cost-effectiveness concerns. The improvement of cancer immunotherapies currently available requires an increase in the effectiveness of CAR T-cells in managing refractory and solid cancers. This could be achieved by using CAR T-cells to target various antigens, enhancing their local delivery and tumour infiltration capabilities and utilizing CAR T-cells in combination with checkpoint blockade and immunotherapy, such as PD-1 blockade and CD19 CAR T-cell combined therapy. Although CAR T-cell treatment offers a lot of promise, its cost needs to be taken into account, especially in healthcare systems with limited funding. More importantly, frameworks for Health Technology Assessment (HTA) must adapt to incorporate ethical, sociological and psychological aspects. Reducing CAR T-cell toxicity is also essential, as it remains among biggest obstacles to their widespread application in clinical practice. Future research should therefore focus on enhancing our understanding of CAR T-cell therapy and expanding the application of immunotherapy in treatment.

C. Kurmann, A. Mujanović, M. Beyeler, Leander Clénin, Philip L. Becker, R. Rohner, Richard McKinley, Shaokai Zheng et al.

Background: Allergic scalp contact dermatitis (ASCD) is a delayed type of hypersensitivity from contact with a specific allergen to which the patients has developed a specific sensitivity. The aim of the study was to evaluate the results of patch testing with standard series of contact allergen in patients suspected to have ASCD. Methods: 112 cases of scalp contact dermatitis were included in the study. Test substances were applied on the upper part of the patient's back, on clinically uninvolved and untreated skin. The patch test was removed and reaction were evaluated after 48 h and 72 h. The grading of negative (-) to positive (+ to ++++) patch test was done in accordance with the International Contact Dermatitis Research Group. Results: Among the 112 cases, 83 patients were female (74.1 %) and 29 were male (25.9 %). The age of participants spanned 17 to 72 years. The commonest age group affected was 41-50 years. The most common positive reactions were recorded to nickel sulphate 22 (26.2%), cobalt chloride 18 (21.4%), fragrance mix 16 (19%), balsam of Peru 14 (16.7%), carba mix 8 (9.5%) and paraphenylenediamine 5 (5.9%).  Females were more likely to show a positive response to two or more allergens. Scalp itching or burning were reported as the most common symptom. Conclusions: Scalp ACD predominantly affects middle-aged women. Our results suggest that nickel sulphate and cobalt are the predominant allergens responsible for the induction of ASCD. These findings are crucial in the treatment, long term management, and education of patients with ASCD.

Amila Mujezinović, Melisa Čajtinović, Alma Dizdarevic, Edina Kuduzović, E. Hadžić

Although persons with intellectual disabilities are entitled to sexual education and freedom of sexual expression, they are often discriminated against in this area and denied access to appropriate education. The attitudes of professional staff play a crucial role in shaping how sexuality is addressed in educational, social and care settings. Supportive and informed professional attitudes are essential for promoting healthy sexual development and safeguarding the well-being of persons with intellectual disabilities. The aim of this study was to examine the attitudes of professional staff who provide support to persons with intellectual disabilities toward the sexuality in relation to the respondents’ gender and age. To assess professionals’ attitudes toward the sexuality of persons with intellectual disabilities adopted version of ASQ-ID (Attitudes to Sexuality Questionnaire – Individuals with an Intellectual Disability) developed by Cuskelly and Gilmore (2007) was used. The study included a sample of 90 respondents (various profiles of professional staff who providing support to persons with intellectual disabilities). The results showed that there are differences in the attitudes of professional staff in relation to the age of respondents, while no statistically significant differences were found in relation to gender of professional staff.

Matthew A. Hunt, Sven David Arvidsson, Gustaf Wängberg, Zhening Zhang, Zerina Kurtović, E. Krock, Lisbet Haglund, Camilla I. Svensson

Marin W F Hoekstra, Rianne Boenink, M. Bonthuis, Brittany A Boerstra, Megan E Astley, Iris R Montez de Sousa, N. Gjorgjievski, H. Resić et al.

The European Renal Association (ERA) Registry collects data on patients with kidney failure receiving kidney replacement therapy (KRT). This paper presents a summary of the ERA Registry Annual Report 2023, and focuses specifically on comparisons by age. The complete ERA Registry Annual Report 2023 is available in the Supplementary information. For 2023, data was collected from 34 countries in Europe and countries bordering the Mediterranean Sea. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities, and expected remaining lifetimes were calculated. In 2023, the ERA Registry covered 519 million people in the participating countries. The incidence of KRT was 151 per million population (pmp). Among incident patients, 29% were aged ≥75 years, 64% were male, and the most common primary renal disease (PRD) was diabetes mellitus (22%). The majority of patients (83%) started KRT with haemodialysis (HD), 11% started with peritoneal dialysis (PD), and 6% underwent pre-emptive kidney transplantation. On 31 December 2023, the prevalence of KRT was 1,101 pmp. Among prevalent patients, 24% were aged ≥75 years, 62% were male and the most common PRD was of miscellaneous origin (18%). Moreover, 56% of prevalent patients received HD, 5% received PD, and 39% were living with a functioning graft. In 2023, the kidney transplantation rate was 43 pmp, with 69% of kidneys coming from deceased donors. For patients starting KRT between 2014 and 2018, 5-year survival probability was 51%. The proportions of incident and prevalent patients aged ≥75 varied considerably across European countries. In addition, incident patients aged ≥75 were more often male, and had more often hypertension as PRD compared with younger patients. Only 1% of incident patients aged ≥75 received a pre-emptive kidney transplant, while among prevalent patients of the same age, 22% was living with a functioning graft.

D. Aiudi, A. Iacoangeli, Andrea Mattioli, S. Russo, Massimo Balbi, S. Vecchioni, M. Luzi, Roberto Trignani et al.

OBJECTIVE Endoscopic endonasal transsphenoidal pituitary surgery is a diffuse and well-established surgical technique: over the years, the transseptal approach via a nasal mucosal incision has also gained popularity. Here we describe our preliminary experience with an entirely endoscopic one-nostril transseptal transsphenoidal approach (EONOTTA) for pituitary sellar tumor resection; the surgical corridor runs through the entire length of the nasal septum via an incision in the nasal mucosa. METHODS A total of 40 patients with a midline prevalent pituitary tumor who underwent EONOTTA from January 2022 to June 2023 were retrospectively reviewed for the evaluation of the safety and efficacy of this technique. RESULTS At 1 year follow-up, all patients had no recurrence, and the degree of tumor resection was comparable to that of the control group undergoing the traditional endoscopic endonasal approach. A low rate of nasal and post-surgical complications occurred; globally, EONOTTA was not time-consuming, and a better functional result was noticed, with a better quality of life for patients. CONCLUSIONS This study confirms, in our preliminary experience, the EONOTTA's excellent risk-benefit ratio in selected cases; for an experienced multidisciplinary team, it provides a good maneuverability and a functional outcome while preserving the integrity of the nasal mucosa.

Background Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related disorders, but inappropriate or prolonged use carries potential health risks. Physicians, due to their access to medication and clinical knowledge, may be prone to self-medicating with PPIs without appropriate oversight. Objective To assess the prevalence and patterns of personal PPI use and self-medication among practicing physicians in Bosnia and Herzegovina, and to identify demographic and professional predictors of such behavior. Methods A cross-sectional, questionnaire-based survey was conducted among 448 physicians who responded to the study invitation, out of approximately 600 invited, from various healthcare levels in Bosnia and Herzegovina between January and May 2025. The survey collected data on PPI use history, consultation behavior, awareness of adverse effects, and adherence to treatment guidelines. Multivariable logistic regression was used to identify independent predictors of self-medication. Results A total of 65.4% of respondents reported past PPI use, during their medical practice, and 31.7% were current users. Over half (52.2%) admitted using PPIs without consulting another physician, and only 17.4% referred to clinical guidelines prior to use. Occasional use was the most common pattern (59.0%), while adverse effects were rarely reported (1.8%). No demographic or professional variable was significantly associated with self-medication with PPIs (defined as PPI use without consulting another physician) in the multivariable analysis. Conclusion Self-medication with PPIs is highly prevalent among physicians and frequently occurs without clinical consultation or adherence to guidelines. This behavior appears to be widespread across age groups, sexes, and care levels, highlighting the need for institutional interventions that promote rational prescribing and raise awareness about responsible self-care within the medical profession.

Martina Zangger, K. Jungo, Limor Adler, R. Assenova, Olivera Batić-Mujanović, L. Bracchitta, Christine Brütting, K. Buczkowski et al.

Background The long-term use of beta blockers after myocardial infarction in patients with preserved ventricular function is debated. General practitioners (GPs) often decide whether to continue or discontinue long-term medications, yet little is known about how they apply evolving evidence to clinical prescribing decisions. Objective To assess whether GPs are willing to deprescribe beta blockers post myocardial infarction with preserved left ventricular function and to identify factors associated with deprescribing decisions. Design Cross-sectional online survey using case vignettes, conducted between July 2023 and October 2024 in primary care settings in 24 sites across 20 European countries. Participants Practicing GPs recruited through convenience sampling at each site. Main measures The primary outcome was whether the GP chose to deprescribe beta blockers in the vignettes. Adjusted risk ratios for the association between GP characteristics and the decision to deprescribe were estimated using Poisson regression with generalized estimating equations and robust standard errors, accounting for clustering at the GP and country level. Key results 604 GPs participated in the survey (median [IQR] age, 44.0 [35.0-54.8] years; 364 [60.3%] female), 89.2% deprescribed beta blockers in at least one vignette. The likelihood of deprescribing increased with time since myocardial infarction (adjusted risk ratio [RR] = 1.28; 95% CI 1.21–1.36 after 5 years; RR = 1.78; 95% CI 1.66–1.90 after 10 years vs. 3 months) and with side effects (RR = 1.76; 95% CI 1.66–1.88). More years of clinical experience were associated with a lower likelihood of deprescribing (RR = 0.86; 95% CI 0.77–0.95 for most vs. least experienced). Conclusions In this cross-national vignette study, most GPs were willing to deprescribe beta blockers after myocardial infarction in patients with preserved left ventricular function, particularly when time had passed and side effects were present. These findings suggest that GPs are open to applying evolving evidence on beta blocker discontinuation in clinical care. Supplementary Information The online version contains supplementary material available at 10.1186/s12875-026-03208-6.

Ivana Bočina, Nives Kević, Ivana Restović, Leo Jerčić, Marinela Jelinčić Korčulanin, Katarina Vukojević, N. Filipović

Pannexins are transmembrane glycoproteins that share structural and functional similarities with the gap junction proteins innexins and connexins. They play a critical role in paracrine and intracellular signalling, including purinergic signalling via the release of extracellular ATP. The role of pannexins in renal function and the pathophysiology of renal diseases is being intensely studied. However, there are no data on the subcellular localization of pannexin 1 expression in the rat kidney. We studied the distribution of pannexin 1 in the rat kidney, combining light microscopy with immunofluorescent immunohistochemistry and transmission electron microscopy with immunogold pannexin labelling. We found strong expression of pannexin in glomerular podocytes, proximal tubules and collecting ducts; moderate expression in the endothelium of glomerular and peritubular capillaries; thin descending and thick ascending limbs of the loop of Henle; and weaker pannexin 1 expression in the distal tubular epithelium. We described the detailed ultrastructural localization of pannexin 1 expression. This is the first study describing the ultrastructural distribution of pannexin 1 in the rat kidney, one of the most used preclinical models in renal physiology and pathology research. These results provide previously missing data on the precise distribution of pannexin 1 in the rat kidney, which is a prerequisite for a proper understanding of its role in renal physiology and pathophysiology.

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