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S. Loga-Zec, A. Klobučar, O. Lepara, G. Sulejmanpasić, A. Memić-Serdarević, Nataša Loga-Andrijić

BACKGROUND Schizophrenia (SCH) is a severe neuropsychiatric disorder associated with complex neurobiological alterations and suboptimal therapeutic outcomes. Increasing evidence indicates that mitochondrial dysfunction may contribute to SCH pathophysiology through impaired energy metabolism, oxidative stress, altered calcium homeostasis, and dysregulation of neuronal function. This review aims to summarize current knowledge regarding mitochondrial abnormalities in schizophrenia and to explore their potential involvement in the mechanisms of action of antipsychotic drugs. SUBJECTS AND METHODS A comprehensive review of the current literature was performed, focusing on human studies, cellular and animal models investigating mitochondrial alterations in schizophrenia, as well as studies evaluating the effects of antipsychotic medications on mitochondrial structure and function. RESULTS Available evidence demonstrates structural, molecular, and functional mitochondrial abnormalities in schizophrenia, including alterations in mitochondrial density, respiratory chain activity, oxidative phosphorylation, ATP production, and redox regulation. Antipsychotic drugs influence mitochondrial pathways in a complex and drug-specific manner. Some antipsychotics may impair mitochondrial respiration and increase oxidative stress, whereas others may exert compensatory or protective effects. Mitochondrial alterations may also contribute to cognitive impairment, negative symptoms, treatment response variability, and metabolic adverse effects associated with antipsychotic therapy. CONCLUSIONS Mitochondrial dysfunction represents an important component of schizophrenia pathophysiology and a potential therapeutic target. The interaction between mitochondrial pathways and antipsychotic drug effects highlights mitochondria as a possible pharmacodynamic interface for personalized treatment strategies. Further in vivo studies and biomarker-based approaches are required to clarify drug-mitochondria interactions and improve therapeutic outcomes in schizophrenia.

Afsaneh Eghbali, P. Kärhä, E. Ikonen, I. Kröger, Michael Rauer, S. Reichmuth, Jochen Hohl‐Ebinger, Gabriele Friesen et al.

Eylem Bektaş Bilgiç, B. Güzel, Fatma Işbilir, Aycan Korkmazcan, Y. Altundağ, N. Hadžiomerović, O. Gündemir

Simple Summary This study examined whether two neighboring areas on the inner surface of the skull base differ in three native sheep breeds. These areas are difficult to study using traditional methods, but imaging techniques allowed us to examine them in detail. We found differences between breeds in both size and shape, although the differences in shape were more noticeable. The two regions were partly independent but also changed together in a coordinated way. In contrast, their sizes were not strongly related. Overall, the results show that subtle differences between breeds can be detected even in hidden parts of the skull. They also suggest that nearby areas of the skull base are connected in how they vary, which may be useful for future studies of skull structure and development.

A. Belančić, S. Şener, Marija Rogoznica Pavlović, Mirjana Stanić Benić, Y. Şener, A. Fajkić, M. Vučković, J. Radić et al.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by debilitating pain and progressive joint destruction. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine, has been implicated in modulating both peripheral and central pain pathways. TNF-α inhibitors, initially developed to halt structural damage in RA, have demonstrated substantial efficacy in pain relief, independent of their anti-inflammatory properties. This narrative review explores the mechanistic pathways through which TNF-α contributes to pain sensitization and highlights the role of TNF-α inhibitors in disrupting these pathways. Evidence suggests that these biologics not only reduce synovial inflammation but also modulate neuroinflammatory circuits, altering pain perception at the spinal and supraspinal levels. Despite their clinical success, variability in patient response and concerns regarding long-term safety necessitate further research into personalized therapeutic strategies. Identifying biomarkers predictive of pain relief could enhance treatment precision. Ultimately, the integration of TNF-α inhibitors into multidisciplinary pain management approaches holds promise for improving clinical outcomes and quality of life in RA.

Birgit Steiner-Zitzenbacher, Christina Karner, Andreas Uellen, Viktoria Holzer, D. Vejzović, M. Balić, J. Szkandera, Bernadette Liegl-Atzwanger et al.

Cancer therapy remains challenged by limited treatment efficacy, cancer-related malnutrition and substantial toxicity, underscoring the need for novel strategies to improve therapeutic responses. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), exhibit both nutritional and bioactive properties, including anti-inflammatory effects and the ability to enhance tumor cell susceptibility to oxidative stress and ferroptosis. To improve stability and delivery, omega-3 fatty acids can be formulated into nanoemulsions that facilitate cellular uptake and may potentiate anticancer therapies. Therefore, we developed a panel of nanoemulsions with defined omega-3 and 9 fatty acid profiles derived from algae, fish and olive oils. All formulations exhibited high physicochemical stability, nanoscale droplet sizes and compendial quality. While pure oil showed minimal biological activity, nanoemulsification markedly increased cytotoxicity, and the novel DHA-rich algae oil emulsion displayed strong and selective antitumor effects without affecting normal fibroblasts. Combination studies indicated tumor type-dependent enhancement of chemotherapeutic efficacy. RNA sequencing indicated activation of ferroptosis-associated pathways and suppression of DNA replication and cell-cycle progression by the novel DHA-rich algae oil emulsion. To expand translational relevance for tumor specific target therapies, a HER2⁺/ER⁻ patient-derived breast cancer cell line and matched cancer-associated fibroblasts were established and characterized. In conclusion, these findings identify the new formulation prototype as a selective and biologically active nanocarrier for DHA which is capable of enhancing tumor type specific therapies, selective chemotherapeutic efficacy and potentially inducing ferroptosis-driven antiproliferative programs. These results highlight the promising potential of DHA as lipid component in a nanoscale droplet size formulation for future combination cancer therapies.

ABSTRACT Introduction: Repaired TOF (rTOF) is a common condition in adult congenital heart disease care. The aim of this article is to investigate how inflammatory markers and volume overload affect rTOF, and how these factors correlate with echocardiographic findings in the right heart cavities. Methods: This study included 32 adult patients (mean age, 27.44 ± 6.22 years) who had undergone surgical correction of TOF during infancy. All participants underwent transthoracic echocardiography, and laboratory assessments included measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP; reference range ≤125 pg/mL) and high-sensitivity C-reactive protein (hs-CRP; reference range ≤2.0 mg/L). Results: Significant correlations were found between NT-proBNP levels and right ventricular (RV) fractional area change (FAC) (r = −0.55, P = 0.001), tricuspid annular plane systolic excursion (TAPSE) (r = −0.35, P = 0.04), RV basal diameter (r = 0.47, P = 0.006), and right atrium (RA) area (r = 0.50, P = 0.003). Similarly, hs-CRP levels showed strong associations with RV FAC (r = −0.58, P < 0.001), TAPSE (r = −0.45, P = 0.009), RV basal diameter (r = 0.43, P = 0.01), and RA area (r = 0.43, P = 0.01). NT-proBNP had a significant impact (P = 0.017; EXP B = 0.982) on RV FAC. A decrease of 10 units in NT-proBNP was associated with a 17% reduction likelihood of having RV FAC <35%. Conclusion: The proinflammatory response (hs-CRP) and volume load (NT-proBNP) are directly correlated with echocardiographic parameters of the right heart cavities in patients with rTOF, suggesting that patients may benefit from treatment with anti-inflammatory drugs, as well as medications targeting diastolic dysfunction.

J. Suljagić, Edita Bjelić, M. Suljkanović, S. Papović, J. Cerar, M. Vraneš

Hydrophobic eutectic solvent systems (ESSs) were prepared and characterized using temperature-dependent thermophysical and transport property measurements, supported by thermal analysis. The investigated systems comprise terpene-based mixtures, menthol:octanoic acid (1:2) and menthol:decanoic acid (1:1), and thymol-based mixtures, thymol:butanol (1:1), thymol:hexanol (1:1), thymol:octanoic acid (1:1), and thymol:oleic acid (1:1), as well as salt-containing ESSs based on tetrabutylphosphonium bromide (TBPBr), TBPBr:octanoic acid (1:1), and TBPBr:lauric acid (1:1). Density, dynamic viscosity, and electrical conductivity were measured at atmospheric pressure (p = 0.1 MPa) over 293.15–313.15 K. From density data, molar volumes and isobaric thermal expansion coefficients were calculated. The temperature dependence of viscosity was correlated with both Arrhenius and Vogel–Fulcher–Tammann equations. Conductivity results were used to compute molar conductivities, and the coupled conductivity–viscosity behavior was assessed via Walden analysis to quantify deviations from ideal electrolyte behavior and estimate ionicity. Thermal behavior and stability were evaluated by differential scanning calorimetry (DSC) and simultaneous thermogravimetric analysis (TG/DSC). The resulting dataset enables a consistent comparison of volumetric, flow, and ion transport descriptors across fully molecular terpene-based mixtures and TBPBr-containing systems. Overall, the combined transport descriptors, including Walden analysis, provide a practical framework for distinguishing molecular from salt-containing hydrophobic ESS families and support formulation selection for temperature-dependent applications, particularly in biphasic extraction processes.

OBJECTIVE To evaluate the level of insight into illness in patients with schizophrenia and its associations with demographic factors, clinical symptoms, executive functions, and selected metabolic parameters. SUBJECTS AND METHODS This cross-sectional study included 60 outpatients diagnosed with schizophrenia according to DSMIV criteria. Participants were divided into two groups based on the median score of the Self-Appraisal of Illness Questionnaire (SAIQ): preserved insight (n=30) and impaired insight (n=30). Positive symptoms were assessed with the Positive Symptoms Rating Scale (PSRS), negative symptoms with the Brief Negative Symptom Assessment (BNSA), executive functions with the Wisconsin Card Sorting Test (WCST) and Wechsler-Bellevue Intelligence Scale-II (WB-II) subscales. Metabolic parameters included body mass index (BMI), systolic and diastolic blood pressure, and waist circumference. Statistical analysis was performed using t-tests, ANOVA, Pearson correlation, and multiple linear regression (p<0.05). RESULTS Patients with impaired insight exhibited significantly higher positive (PSRS: 28.5±4.2 vs 18.3±3.1; p<0.001) and negative symptoms (BNSA: 35.2±5.6 vs 22.1±4.0; p<0.001), poorer executive performance (WCST total score: 45.6±8.9 vs 68.4±7.2; p<0.001), higher BMI (28.7±3.4 vs 24.5±2.8; p<0.01), and elevated blood pressure values. SAIQ total score negatively correlated with positive (r=-0.62; p<0.001) and negative symptoms (r=-0.58; p<0.001), illness duration (r=-0.45; p<0.01), and positively with years of education (r=0.48; p<0.01) and WCST score (r=0.52; p<0.001). Regression analysis showed that negative symptoms (β=-0.41; p<0.001) and executive dysfunction (β=-0.35; p<0.01) were the strongest independent predictors of poor insight (R²=0.62). CONCLUSION Impaired insight in schizophrenia is strongly associated with greater psychopathological burden, neurocognitive deficits (especially executive dysfunction), and metabolic disturbances. These findings support the implementation of integrated therapeutic strategies targeting insight, cognition, and cardiometabolic health to improve long-term outcomes.

A. Haskic, N. Hadžiabdić, R. J. Miron

Postoperative sequelae such as pain, swelling, and trismus are common following mandibular third molar surgery. This single-blind controlled trial was performed to evaluate the effects of two newer platelet-rich fibrin (PRF) formulations, horizontal PRF (H-PRF) and extended PRF (E-PRF/albumin-PRF), on soft tissue healing and postoperative complications. Sixty-seven ASA class 1 patients aged 16-30 years were assigned to the H-PRF, E-PRF, or control (natural coagulum) group, with 60 completing the study. The primary outcome was soft tissue healing, while secondary outcomes included pain, analgesic use, swelling, trismus, alveolar osteitis, and infection. The PRF formulations did not significantly improve soft tissue healing during the first postoperative week (day 3: P = 0.64; day 7: P = 0.22). On day 7, the H-PRF group showed a significantly reduced trismus when compared to the control group (P = 0.017). No significant differences were observed in terms of pain, swelling, or analgesic consumption (all P > 0.05). A significantly reduced trismus observed with H-PRF suggests potential clinical benefits; however, further studies with larger samples are needed to confirm these findings and their clinical relevance.

Alejandro Flores-Manzanero, W. Bogdanowicz, M. Stefanović, Roya Adavoudi, Rasoul Khosravi, Francelly Martínez‐Sosa, K. Doan, Y. Srinivas et al.

Rapid global changes in climate and habitats lead to shifts in species' geographic ranges. Range contractions experienced by numerous species may result in local extinctions and connectivity disruptions. In some species, range expansions have been observed instead, suggesting the enlargement of suitable habitats and/or adaptations to changing environments. Despite its importance for wildlife management, our understanding of the factors influencing species' spatial responses to rapidly changing environments remains limited. The golden jackal serves as an excellent model to address this knowledge gap, given its ongoing rapid range expansion. In this study, we investigated environmental factors contributing to genetic connectivity and local adaptation across the expanding range of the golden jackal, based on a comprehensive sampling scheme across Eurasia (n = 363), a high‐quality set of genomic markers (19,746 SNPs), and a landscape genomics framework. At the continental scale, geographic distance emerged as the predominant factor. At finer spatial scales, genetic connectivity was best explained by climatic predictors, specifically high annual and seasonal variations in precipitation and temperature, which can shape the species' spatial genetic structure by constraining gene flow. Our connectivity models for current and future climatic conditions show that the species' northward expansion is facilitated by changes in these variables in central and northern Europe promoting high connectivity. Precipitation and temperature were also responsible for most local adaptation signals. Given the potential role of hybridization with domestic dogs in shaping range expansion patterns, we investigated the association between environmental conditions and dog admixture proportions. We found no significant trends, indicating a limited effect of dog admixture on habitat choice. Collectively, our findings suggest that the golden jackal has the potential to continue its expansion across Eurasia in response to ongoing global climate change, providing an example of a species that rapidly tracks the expansion of its suitable habitats.

1. 4. 2026.
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Darije Custovic, A. Custovic, James E. Gern, S. Saglani, S. Fontanella

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