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Iris Menu, Mark Duffy, Tanya Bhatia, Sofia Trapaga, J. John, Selma Musić, D. Nicholas, Seyeon Yim et al.

Preterm birth can significantly impact cognitive development, particularly executive functions (EF). This study investigated hot (with emotional/motivational aspects) and cool (purely neutral/cognitive) EF trajectories in preterm and full-term children, examining brain-behavior relationships. It included 3508 participants aged 9–10 years (mean age 10.0 years) at baseline from the Adolescent Brain and Cognitive Development (ABCD®) study, evenly split between preterm and full-term births (54.36 % males; 1.05 % Asian American, 10.69 % Black, 15.68 % Hispanic, 61.57 % White, 11.09 % other). Participants were followed for 4 years, completing MRI scans and a cool EF task at baseline and at the 2-year follow-up, as well as hot/cool and hot EF tasks at the 1- and 3-year follow-ups. Linear mixed models showed varying effects of preterm birth across the different EF tasks. Specifically, preterm children showed persistent cool EF deficits and a catch-up pattern for hot EF, while performance on the hot/cool task showed no association with preterm birth. Brain-behavior bivariate latent change score analyses identified distinct bidirectional relationships in specific regions, suggesting altered cognitive-brain maturation interactions in preterm children. These findings highlight the complex nature of EF development following preterm birth: while cool EF deficits persist, hot EF shows catch-up growth in preterm children during early adolescence. This emphasizes the need for tailored interventions and long-term follow-up in this population.

Peter Møller, E. E. Bankoglu, Helga Stopper, G. Gajski, Marko Gerić, A. Haverić, A. Azqueta, Lisa Giovannelli et al.

Exposure to heavy metals such as lead, arsenic and chromium is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed effects of heavy metal exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. We distinguish between traditional toxic metals (lead), semi-metals/metalloids (arsenic), transition metals (chromium), and other heavy metals. The literature search led to 66 studies, which were assessed by meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to lead (1.99, 95 % CI: 1.47, 2.51), arsenic (1.36, 95 % CI: 0.94, 1.77), chromium/welding fume (2.03, 95 % CI: 1.48, 2.57), and other heavy metals (0.81, 95 % CI: 0.45, 1.18). Subgroup analysis indicates that all studies combined from middle-income countries have higher effect size (1.99, 95 % CI: 1.63, 2.35) than have studies from high-income countries (0.81, 95 % CI: 0.37, 1.26). The lower effect size in high-income countries may be due to differences in exposure levels, related to stricter regulation of emissions or more awareness/use of personal protective equipment in the working environment. Sensitivity analysis does not unequivocally link effect size to comet assay measurement bias, inferred by insufficient information on comet assay procedures, missing assay controls, non-blinded analysis of samples, or exposure misclassification. In conclusion, this systematic review and meta-analysis shows that exposure to heavy metals - lead, arsenic and chromium - is associated with increased levels of DNA strand breaks in human leukocytes.

E. Campara, Edina Lazović-Salčin, A. Skopljak, Merita Tiric - Campara

PEComa (Perivascular epithelioid cell tumors) are a rare type of tumor composed of cells exhibiting characteristics of smooth muscle cells and melanocytes. They most commonly occur in the female genital system. This study is a narrative review based on the differential diagnosis of tumors in the female genital system, focusing on PEComa. The aim of the research is to analyze the immunohistochemical markers characteristic of PEComa in the female genital system and compare them with markers of tumors that may appear in the differential diagnosis. Specifically, the study examines epithelioid smooth muscle tumor (STUMP), malignant melanoma, alveolar soft part sarcoma (ASPS), poorly differentiated endometrial carcinoma (EC) and trophoblastic tumors of the placenta (PSTT). Comparison of immunohistochemical markers of PEComa with markers of other tumors revealed that: PEComas show overlap in positive staining with STUMP, but are distinguished by markers such as HMB45, PNL2, MiTF, and MelanA/MART1; PEComas share some melanocytic markers with malignant melanoma, but differ in the expression of myogenic markers and hormone receptors; compared to ASPS, PEComas share some positive staining but differ in marker expression and negative staining; they differ from EC by the expression of specific markers such as MiTF and PAX8; PSTT show specificity for markers of trophoblastic differentiation and implantation, while PEComas emphasize melanocytic and myogenic differentiation. The general conclusion is that an accurate diagnosis of PEComa in the female genital system can only be achieved through a multidisciplinary approach. Immunohistochemical evaluation serves as a helpful tool, but standard morphological staining remains the gold standard. Also, the advanced diagnostic techniques, particularly next-generation sequencing, hold promise for enhancing the understanding and management of mPEComas. By uncovering the genomic landscape and facilitating targeted therapies, these methodologies may lead to more effective treatment and improved outcomes. Keywords: female genital system, epithelioid smooth muscle tumor, malignant melanoma, endometrial carcinoma, trophoblastic tumor.

Sonja T Marinković, Tanja Sobot, Ž. Maksimović, Ðorđe Ðukanović, S. Uletilović, N. Mandić-Kovačević, Sanja Jovičić, Milka Matičić et al.

Autonomic imbalance is one of the major pathological disturbances in chronic heart failure (CHF). Additionally, enhanced oxidative stress and inflammation are considered to be the main contributors to the disease progression. A growing body of evidence suggests cholinergic stimulation as a potential therapeutic approach in CHF, since it corrects the autonomic imbalance and alters the inflammatory response via the cholinergic anti-inflammatory pathway. Although previous research has provided some insights into the potential mechanisms behind these effects, there is a gap in knowledge regarding different cholinergic stimulation methods and their specific mechanisms of action. In the present study, an isoprenaline model (5 mg/kg/day s.c. for 7 days, followed by 4 weeks of CHF development) was used. Afterwards, rats received pyridostigmine (22 mg/kg/day in tap water for 14 days) or no treatment. Pyridostigmine treatment prevented the progression of CHF, decreasing chamber wall thinning (↑ PWDd, ↑ PWDs) and left ventricle dilatation (↓ LVIDd, ↓ LVIDs), thus improving cardiac contractile function (↑ EF). Additionally, pyridostigmine improved antioxidative status (↓ TBARS, ↓ NO2−; ↑ CAT, ↑ GSH) and significantly reduced cardiac fibrosis development, confirmed by pathohistological findings and biochemical marker reduction (↓ MMP2, ↓ MMP9). However, further investigations are needed to fully understand the exact cellular mechanisms involved in the CHF attenuation via pyridostigmine.

Jelena Komić, Nela Kelam, Anita Racetin, N. Filipović, M. Saraga-Babic, Dai Ihara, Yu Katsuyama, Katarina Vukojević

Congenital anomalies of the kidney and urinary tract (CAKUT) are the third most common congenital anomaly and a significant public health concern. It is the predominant cause of chronic renal disease in pediatric populations and the principal reason for kidney replacement therapy in individuals under 20, as well as the fourth leading cause in adults. Five candidate genes, including EDA2R, PCDH9, and TRAF7 were identified as potential contributors to CAKUT. These genes had not been previously prioritized in CAKUT research, and our prior studies have demonstrated that the proteins encoded by these candidate genes display dysregulated expression across various CAKUT subgroups. Our research examined the expression patterns of EDA2R, PCDH9, and TRAF7 in yotari (Dab1−/−) mice at two embryonic stages (E13.5 and E15.5) and two postnatal stages (P4 and P14) to ascertain the potential correlation between Reelin–Dab1 signaling, previously linked to CAKUT phenotypes, and the aforementioned proteins through molecular and morphological analyses. All three observed proteins exhibited the highest area percentage at E13.5, with a trend of decline into postnatal stages, during which specific changes in protein expression were noted between the cortex and medulla of yotari mice compared to wild-type mice. For TRAF7, a statistically significant difference in area percentage at E13.5 was observed, indicating a link with Reelin–Dab1 signaling and a potentially critical role in the pathophysiology of CAKUT, also marked by our prior study.

N. Šabanović-Bajramović, Mirna Aleckovic-Halilovic, Larisa Dizdarevic-Hudic, Sevleta Avdić, L. Kos, Bojan Stanetic, Ammar Brkić, Bojan Pejović et al.

Due to an epidemic of risk factors, such as hypertension, and an increase in life expectancy, cardiovascular disease (CVD) has an overwhelming morbidity and mortality burden worldwide. Various treatment options are available to disrupt pathophysiological processes along the cardiovascular continuum by focusing on distinct regions of the renin-angiotensin-aldosterone system (RAAS). As a RAAS inhibition, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are recommended first-line treatments for hypertension and CVD. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Furthermore, a number of studies have shown that RAAS blockade can lower cardiovascular risk in ways that go beyond what could be predicted from lowering blood pressure alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. In high cardiovascular risk patients, telmisartan reduces cardiovascular events in a manner comparable to that of the ACE inhibitor ramipril beyond lowering blood pressure alone, but with better tolerability. Research points to possible benefits for adipose tissue activity, neurovascular function, and enhancements in glucose and lipid metabolism. According to several studies, telmisartan has partial peroxisome proliferator-activated receptor gamma (PPARγ) agonist activity, which improves insulin resistance in diabetic patients by modifying adipokine levels. The combination of telmisartan and indapamide as metabolically neutral diuretic has an additional positive antihypertensive as well as cardioprotective effects. In addition to reviewing current CVD management guidelines, this article will examine important clinical trial and clinical practice data that assess the role of telmisartan/indapamide in CVD. Keywords: arterial hypertension, angiotensin II receptor blocker, telmisartan, cardiovascular risk.

A. Párniczky, A. Mikó, Aliye Uc, A. Singh, A. Elhence, A. Saluja, Atsushi Masamune, B. A. Abu Dayyeh et al.

INTRODUCTION The International Association of Pancreatology, alongside the American Pancreatic Association, the European Pancreatic Club, the Indian Pancreas Club, and the Japan Pancreas Society, decided to update its earlier guidelines for the management of acute pancreatitis (AP) given the remarkable advances in our understanding of AP and its management over the last decade. METHODS These organizations put together a group of international experts to address important issues related to the management of AP. Guideline Development Groups comprising international domain experts framed clinically relevant questions and conducted thorough literature searches and systematic reviews to address the questions. Questions were framed in the PICO (Participant, Intervention, Comparator, and Outcome) format where appropriate. The evidence from the literature was synthesized to develop evidence-based recommendations for each question. The quality of evidence and the strength of the recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). For some questions, we have provided Good Practice Statements if enough direct evidence was unavailable. RESULTS The guidelines pertain to 18 domains comprising 96 questions. The recommendations cover almost all aspects of managing AP, including pain control, fluid therapy, patient stabilization, nutritional support, conservative and interventional treatment for infected necrotizing pancreatitis, management of complications, discharge criteria, guidance on follow-up, and strategies for prevention of recurrence. Specific types of AP, such as those associated with pregnancy, trauma, and metabolic factors have been given special attention. CONCLUSION The recommendations presented here should serve as an evidence-based resource for practicing physicians and caregivers to treat patients with AP more effectively. In addition, the guidelines identify areas for future research, mainly targeted therapies for controlling systemic inflammation and mitigating organ dysfunction.

Muhamed Bisić, Adi Pandžić, M. Jusufbegović, Mujo Ćerimović, P. Elek

Recent technological advances have expanded the use of 3D-printed polymer components across industries, including a growing interest in military applications. The effective defensive use of such materials depends on a thorough understanding of polymer properties, printing techniques, structural design, and influencing parameters. This paper analyzes the ballistic resistance of 3D-printed polymer structures against 9 × 19 mm projectiles. Cuboid targets with different infill patterns—cubic, grid, honeycomb, and gyroid—were fabricated and tested experimentally using live ammunition. Post-impact, CT scans were used to non-destructively measure projectile penetration depths. The honeycomb infill demonstrated superior bullet-stopping performance. Additionally, mechanical properties were experimentally determined and applied in FEM simulations, confirming the ability of commercial software to predict projectile–target interaction in complex geometries. A simplified analytical model also produced satisfactory agreement with experimental observations. The results contribute to a better understanding of impact behavior in 3D-printed polymer structures, supporting their potential application in defense systems.

Sabina Zukic, Sadeta Hadžić, N. Babic, N. Avdagić, S. Hasić, Salih Azabagic

Background and objective Type 2 diabetes mellitus (T2DM) is a global health issue that has seen a significant increase in prevalence worldwide. Oxidative stress plays a crucial role in the pathogenesis of numerous chronic diseases. Oxidative stress induced by hyperglycemia has a central role in the development of insulin resistance, as well as micro- and macrovascular complications of diabetes mellitus. This study aimed to investigate the influence of the duration of T2DM on blood glucose levels, glycated hemoglobin (HbA1c), renal function parameters, oxidative stress, and von Willebrand factor (vWf) activity in individuals with diabetes. Methodology A total of 135 participants from both genders with T2DM were included in this study. The participants were divided into three groups based on the duration of their disease: up to five years (46 participants), from 6-10 years (49 participants), and over 10 years (40 participants). The investigated parameters were as follows: fasting glucose, two-hour postprandial glucose, HbA1c, total antioxidant capacity (TAC), glomerular filtration rate (GFR), and vWf activity. Statistical analysis was performed using SPSS Statistics (IBM Corp., Armonk, NY). The Kolmogorov-Smirnov test was applied to assess the normality of distribution. Differences between the groups were analyzed using the Kruskal-Wallis test and analysis of variance (ANOVA), with appropriate post-hoc tests. A p-value <0.05 was considered statistically significant. Results The average age of the participants was 60.86 ± 8.87 years, the average weight was 86 ± 14.6 kg, the average height was 168 ± 9.18 cm, the waist circumference was 99 ± 11.4 cm, the systolic blood pressure was 127 ± 15.6 mmHg, and the diastolic blood pressure was 77 ± 6.7 mmHg. The study revealed statistically significant differences between the groups (p<0.05) for the following parameters: two-hour postprandial glucose (p=0.001), HbA1c (p=0.048), GFR (p=0.038), and vWf activity (p=0.006). No statistical significance was found for TAC values (p>0.05). Conclusions Higher levels of vWf activity were found in people who had been treated for type 2 diabetes for more than 10 years. These findings indicate that the level of vWf activity in people with type 2 diabetes 10 years after the onset of the disease can be used as a marker of vascular pathology.

Traditional medicinal plants are valued for their therapeutic potential, yet the full spectrum of their bioactive compounds often remains underexplored. Recent advances in multiomics technologies, including metabolomics, proteomics, and transcriptomics, combined with in vitro culture systems and elicitor-based strategies, have revolutionized our ability to characterize and enhance the production of valuable secondary metabolites. This review synthesizes current findings on the integration of these approaches to help us understand phytochemical pathways optimising bioactive compound yields. We explore how metabolomic profiling links chemical diversity with antioxidant and antimicrobial activities, how proteomic insights reveal regulatory mechanisms activated during elicitation, and how in vitro systems enable controlled manipulation of metabolic outputs. Both biotic and abiotic elicitors, such as methyl jasmonate and salicylic acid, are discussed as key triggers of phytochemical defense pathways. Further, we examine the potential of multiomics-informed metabolic engineering and synthetic biology to scale production and discover novel compounds. By aligning traditional ethnobotanical knowledge with modern biotechnology, this integrative framework offers a powerful avenue to unlock the pharmacological potential of medicinal plants for sustainable and innovative therapeutic development.

Semir Hrvo, Irma Dizdarevic, Amila Muratspahić, R. Gojak, Berina Hasanefendić, Amir Sandžić, S. Murtić

Introduction. Chronic kidney insufficiency presents a progressive decline in renal function. Long-term hemodialysis treatments lead to biochemical parameter imbalances like an altered level of homocysteine (Hcy). Hcy can contribute to oxidative stress and endothelial damage, which promotes the accumulation of low-density lipoprotein (LDL) cholesterol and the development of atherosclerosis. It can also affect lipoprotein metabolism and trigger inflammatory processes that alter the lipid profile, especially increasing triglycerides and lowering high-density lipoprotein (HDL) cholesterol. Methods. This cross-sectional, clinical and descriptive-analytical study included 83 patients, 40 patients on hemodialysis, and 43 subjects in healthy control group. Results. The hemodialysis group had significantly higher Hcy values compared to the control group of seemingly healthy subjects (p<0.05). The control group had significantly higher values of total cholesterol, LDL and very low-density lipoprotein (VLDL) compared to the hemodialysis patients (p<0.05). There was non significant correlation between Hcy and lipid parameters in the hemodialysis group, neither in the control group. Conclusion. Patients undergoing hemodialysis had significantly higher total homocysteine levels compared to the control group. However, total homocysteine did not demonstrate an association with lipid status parameters in either the hemodialysis patients or the healthy subjects. Keywords: homocysteine, hemodialysis, cholesterol, triglycerides, metabolism.

Abstract Background Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is often linked with reproductive disorders in humans and animals. Despite this, its presence in animals in the Federation of Bosnia and Herzegovina (FB&H) remains undocumented. Objectives This study aimed to investigate the seroprevalence of T. gondii infection among domestic pigs in FB&H, assess associated risk factors for parasite transmission and provide insights into optimal management and biosafety practices for the pig industry. Methods A two‐phase random sampling approach was employed to select 87 pig farms across 10 administrative regions in FB&H. A total of 437 pigs were sampled and tested for anti‐T. gondii antibodies using an indirect ELISA kit. Epidemiological data on potential risk factors were collected through a standardised questionnaire and analysed using logistic regression models. Results The animal‐level seroprevalence was found to be 13.3% (95% CI = 10.4–16.8), with 44.8% of farms testing positive for T. gondii (95% CI: 34.8–55.3). Identified risk factors included exposure to cats, repeated occurrences of abortions within a single breeding season, swill feeding, type of housing, and type of operation. The robust association observed between recurrent abortions and Toxoplasma seropositivity indicates a significantly greater potential involvement of T. gondii in reproductive disorders among pigs in FB&H than previously acknowledged. Conclusions This study provides the first report on T. gondii infection in animals in FB&H, highlighting the need for further research to explore its presence in other meat animals and meat products consumed in the region. The findings underscore the importance of biosafety measures in mitigating T. gondii transmission and call for enhanced surveillance and management strategies in FB&H's pig industry.

Sažetak ( sa ključnim riječima): Sažetak: Radni sporovi su pogodni za rješavanje alternativnim načinima rješavanja, pa i mirenjem propisanim Zakona o mirnom rješavanju radnih sporova iz 2021. godine. U radu se obrađuju specifičnosti radnih sporova kao posebnog parničnog postupka. Glavni fokus rada je na analizi postupku mirnog rješavanja kolektivnih radnih sporova, mirovno vijeće, način određivanja miritelja i arbitara te druga pitanja od značaja za mirno rješavanje radnih sporova za teritoriju Federacije Bosne i Hercegovine ako drugim zakonom nije drugačije određeno. Autorica naglašava važnost obveznog mirenja kod rješavanja kolektivnog radnog spora uz analizu sudske prakse te utjecaj mirenja na ishod parnice i značaj jer postignuti sporazum ima pravnu snagu ovršne isprave. Autorica analizira odnos parničnog zakonodavstva te instituta obveznog mirenja kao predstadija prije pokretanja parničnog postupka za kolektivne radne sporove u kontekstu i konvencijskih prava - prava na pristup sudu te prava na udruživanje i prava na štrajk. Poseban naglasak se stavlja na specifičnosti i značaj mirenja u kolektivnim radnim sporovima. Ključne riječi: kolektivni radni spor, Zakon o mirnom rješavanju radnih sporova, mirenje, arbitraža Summary: Labor disputes are suitable for resolution by alternative means of resolution, including mediation prescribed by the Law on the Peaceful Settlement of Labor Disputes from 2021. The paper addresses the specifics of labor disputes as a special civil procedure. The main focus of the paper is on the analysis of the procedure for the peaceful resolution of collective labor disputes, the peace council, the method of appointing conciliators and arbitrators, and other issues of importance for the peaceful resolution of labor disputes for the territory of the Federation of Bosnia and Herzegovina, unless otherwise provided for by other law. The authors emphasize the importance of mandatory mediation in resolving collective labor disputes, along with an analysis of case law and the impact of mediation on the outcome of litigation and its significance because the agreement reached has the legal force of an enforceable document. The authors analyze the relationship between civil proceeding law and the institute of mandatory mediation as a preliminary stage before initiating civil proceedings for collective labor disputes in the context of both convention rights - the right to access to court and the right to associate and the right to strike. Special emphasis is placed on the specifics and importance of mediation in collective labor disputes. Keywords: collective labor dispute, Law on Peaceful Resolution of Labor Disputes, mediation, arbitratio

S. Živanović, Jelena Pavlović, N. Hadživuković, Susanne Perkhofer, Nertila Podgorica

Dementia is a growing public health problem, particularly in low- and middle-income countries. Bosnia and Herzegovina (BiH), as a post-conflict LMIC with a complex administrative structure, currently lacks national guidelines, epidemiological data, and systematic approaches for dementia care. This study investigates healthcare workers’ attitudes toward dementia care and identifies both obstacles and practical opportunities for improving practice within BiH’s unique healthcare system. A qualitative cross-sectional study was conducted in primary healthcare settings across Bosnia and Herzegovina, with 25 participants, including family medicine doctors (n = 10), nurses (n = 10), and psychologists (n = 5). The data were analyzed using thematic analysis guided by the Consolidated Framework for Implementation Research (CFIR). Dementia care in BiH is predominantly reactive, with healthcare professionals typically responding only after families have expressed concerns. Participants reported inconsistent use of cognitive screening tools (e.g. MMSE, MoCA), largely due to insufficient training, lack of clear national guidelines, and varying institutional practices. Many clinicians felt unprepared and unsupported in managing dementia cases. Cultural stigma and widespread misperceptions of dementia as a normal part of aging contribute to delays in diagnosis and reduce the likelihood that families will seek help early. These barriers are exacerbated by a lack of national prevalence data and fragmented care pathways. The findings of this study indicate the need to change the approach to dementia care in BiH through concrete and realistic measures within the existing systemic frameworks. Practice-based guidelines, culturally adapted tools for early detection, reactivation of community-based care, accessible education, a pragmatic approach to prevention, and local initiatives for awareness-raising and multidisciplinary care are recommended.

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