Background/Objectives: Syncope is a common clinical problem often requiring pharmacological treatment, yet evidence-based therapies remain limited. Midodrine, a vasopressor agent, is frequently used, though its autonomic effects over time remain unclear. This study aimed to assess autonomic nervous system changes and blood pressure response in syncope patients treated with Midodrine, placebo, or their combination. Additionally, the structural properties of the Midodrine placebo were analyzed using nanotechnological methods. Methods: A total of 67 patients with syncope were randomized to receive Midodrine, sucrose placebo, or their combination over three weeks. All participants underwent 24 h Holter ECG with heart rate variability (HRV) analysis and ambulatory blood pressure monitoring before and after therapy. Structural analysis of Midodrine tablets, sucrose, and Midodrine placebo was performed using Raman spectroscopy and X-ray diffraction (XRD). Results: Patients receiving the Midodrine–placebo combination showed a significant reduction in HRV markers of parasympathetic activity (RMSSD, pNN50, HF) and an increase in sympathetic dominance (LF/HF ratio) compared to the other groups. Only this group showed a statistically significant rise in average systolic and diastolic blood pressure. Raman and XRD analyses revealed structural alterations in the sucrose-based placebo compared to its original form, indicating subtle changes in crystalline structure. Conclusions: In this exploratory study, the combination of Midodrine and placebo was associated with autonomic imbalance and modest increases in blood pressure, which may indicate a potential effect in patients with hypotensive syncope phenotypes. These preliminary findings should be interpreted with caution, and the structural modifications observed in the placebo formulation are presented as hypotheses requiring further investigation rather than established mechanisms.

Abstract This study employs EEG and eye-tracking to assess how brand equity, creative complexity, and spatial layout influence implicit consumer responses to point-of-sale (POS) beer advertisements. Through the theoretical lens of predictive coding and processing fluency, laboratory testing with Serbian beer consumers (N = 20) revealed that simpler designs yielded superior attention performance across TFD and TTFF (d up to 2.62), independent of brand strength. Spatial repositioning reduced packshot detection time by 0.89s (p<0.001, d=1.78) in horizontal versus vertical layouts. EEG showed no significant brand differences (valence d=0.07, p=0.765), offering a theoretical interpretation consistent with predictive coding, wherein expected stimuli elicit reduced neural activation, with brand strength operating solely through attentional pathways. Eye-tracking revealed strong brands’ automatic attentional capture of iconic elements (e.g., letter ‘J’; TTFF=0.47s), theoretically reconciled via processing fluency as effortless decoding. We derive actionable POS benchmarks: packshot detection < 0.5s, slogan engagement > 1.0s, emotional valence > 5.0, cognitive load < 5.0. This advances GDPR/NDA-compliant methodology while offering practical guidelines grounded in neurocognitive theory.

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H2O2), super oxide anjon radical (O2−), and nitrogen dioxide (NO2−)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings.

Background/Objectives: Renal failure (RF) and systolic heart failure (sHF) are very often associated with each other, and their synergistic influence can affect the prognosis of acute pulmonary embolism (aPE) patients. The aim of this study is to evaluate the associations between RF, sHF, and in-hospital mortality in patients with normotensive aPE. Methods: We analyzed data from the Regional PE Registry (REPER), and 1968 patients with CT pulmonary angiography-confirmed aPE who had a systolic blood pressure of 100 mmHg and higher, and for whom creatinine blood levels and left ventricular ejection fraction (LVEF) were measured at admission to hospital were enrolled. The patients were divided into four groups: the first group comprised patients without renal and systolic heart failure, the second those with RF (creatinine clearance less than 60 mL/min), the third those with sHF (LVEF less than 50%), and the fourth those with both RF and sHF. The primary endpoint of this study was in-hospital all-cause mortality. Results: There are significant differences between in-hospital mortality among the groups: 38/1247 (3.0%) vs. 63/514 (12.9%) vs. 10/99 (10.1%) vs. 20/108 (18.5%) (p < 0.001). In the multivariable regression model adjusted for age, right ventricular dysfunction, and troponin levels, the presence of renal failure, sHF, and both were independently associated with in-hospital all-cause mortality with ORs of 3.59 (95%CI 2.04–6.30, p < 0.001) vs. 3.97 (1.71–9.25, p = 0.001) vs. 6.39 (3.15–12.99, p < 0.001), respectively. Conclusions: The association of renal failure and systolic heart failure has a deleterious prognosis in patients with normotensive aPE.

OBJECTIVES The presence of altered sagittal cervical balance and faulty posture has been observed in individuals with neck pain. However, there is a lack of literature investigating the relationship between radiological thoracic inlet alignment and clinical sagittal cervico-thoracic posture. This cross-sectional study aims to investigate these clinico-radiological associations, analyze their correlation with pain variables, and explore the diagnostic significance of thoracic inlet parameters for chronic neck pain (CNP). METHODS 88 subjects (N = 44 each in CNP and Control group) were recruited. T1 Slope (T1S), Thoracic inlet angle (TIA), Neck tilt (NT) were assessed on lateral cervical radiograph, and Craniovertebral angle (CVA), High thoracic angle (HTA), Sagittal head angle (SHA) were photographically analysed. Pain was quantified in terms of intensity and functional disability. Craniocervical flexion test (CCFT) assessed the deep neck flexors (DNF) performance. RESULTS After normality check, between-group comparisons utilized Unpaired t-test or Mann-Whitney U test. CNP group had lower T1S, and higher TIA, NT. The TIA had significant correlation with CVA and HTA (rs = -0.32, -0.30 respectively) in asymptomatic group, but not in CNP subjects. Patients with severe pain/disability had weaker DNF. Symptomatic group showed age-related declines in SHA, CVA and CCFT. Logistic regression revealed T1S (<26.36°) and NT (>47.41°) had diagnostic significance for CNP. CONCLUSION Neck pain corresponded with distinct postural, radiological, and clinical alterations compared to controls. Thoracic inlet parameters (primarily TIA) influenced cervicothoracic posture in asymptomatic individuals, but pain disrupted these associations, highlighting the complex interplay between alignment, posture, and symptomatology.

The study aimed to evaluate the audiologic profile of preschool children with hearing loss, i.e., to determine the type, degree, and configuration of hearing loss, amplitude of otoacoustic emissions, and word recognition performance. This retrospective study included 260 children examined in a secondary healthcare setting. For statistical data analysis, we used the Chi-square test with a level of significance p < 0.05. Conductive, sensorineural, and mixed hearing loss was present in 93.1%, 4.6%, and 2.3%, respectively. Mild hearing loss was present in 96.1%, moderate in 2.3%, and severe hearing loss in 1.6%. Type B tympanogram was the most common (p = 0.00001). The mean amplitude of otoacoustic emissions was -7.6 dB in sensorineural hearing loss and 12.3 dB in normal hearing. The maximum word recognition score was frequently obtained at presentation levels of 25-40 dB SL (p = 0.009). The majority of children had mild conductive hearing loss with normal word recognition ability.

This research analyses the influence of welding parameters in pulsed TIG welding on the electrical response of the welding power source, and consequently on heat input and weld geometry. In the experiment, we varied pulse frequency and the proportion of base current. By measuring welding current and arc voltage, we analysed the response of welding power source, determined heat input, and examined weld geometry. The results show that, particularly at higher pulse frequencies, the welding power source fails to follow the intended pulse shape and fails to achieve set values of welding current. This directly affects heat input and weld geometry. Increasing pulse frequency up to 5 kHz results in higher weld penetration depths and weld width, mainly due to higher heat input.

ABSTRACT Increasing oxygen transport through elevated hemoglobin concentration and red blood cell mass is a key objective of blood doping, commonly achieved via recombinant human erythropoietin (rHuEPO) administration or blood transfusions. While the Athlete Biological Passport (ABP) offers an effective indirect tool for detecting such manipulations, its sensitivity and specificity may be limited, particularly in cases involving microdoses or confounding physiological factors. To address these limitations, the identification of novel biomarkers that complement current ABP markers is essential. This study presents a targeted metabolomics approach to discover candidate biomarkers of rHuEPO administration by analyzing polar metabolites in plasma and serum from two administration studies: one involving a single CERA injection, and the other using multiple doses of epoetin delta. Hydrophilic interaction chromatography hyphenated with tandem mass spectrometry enabled the selective and sensitive detection of a panel of polar endogenous metabolites. Following data normalization and stringent quality control, generalized least squares models were applied to evidence temporal changes in metabolite signals. Among the most responsive and concordant markers across both studies were hypoxanthine and inosine, which showed significant and marked increases following rHuEPO administration. Notably, the relative increase of these metabolites coincided with the maximum in reticulocyte percentages, reflecting maximal erythropoietic activity. As intermediates in purine metabolism, their increases are likely tied to augmented purine turnover during red blood cell production. These findings suggest that hypoxanthine and inosine are promising candidate biomarkers to complement existing ABP parameters. However, further validation is required to confirm their reliability and applicability within the ABP framework.

Abstract Despite striking successes in identifying novel biomarkers for improved patient stratification and predicting disease progression, numerous challenges remain in the effective integration and exploitation of multiomic data in biomedical applications beyond cancer, for which most bioinformatics strategies are developed and validated. That focus on cancer severely limits the effective development and advancement of algorithms in machine learning and artificial intelligence that do not suffer degraded out-of-domain performance. Generalizability and interpretability of models, however, are also required for robust insights that may translate into clinical practice. Work across different independent datasets is critical for establishing models robust towards unwanted variation in assays, protocols, and cohort populations. Disease-specific context like ethnicity, socioeconomic background, sex, lifestyle, disease phase, and tissue type also strongly affect molecular profiles. We here discuss atherosclerotic cardiovascular disease (ASCVD) as a high-impact non-cancer use case for the challenges remaining in the development and application of the latest bioinformatics approaches to multiomics data integration. ASCVD remains the leading cause of death globally. Disease aetiology, progression, and therapy outcome depend on a complex interplay of genetic, environmental, and lifestyle factors. Integrating these diverse data types effectively remains a challenge but holds transformative potential for personalized medicine. Discovery and access to data of sufficient diversity and extent form key bottlenecks. We here compile a first comprehensive overview of key data sets in ASCVD to complement the established cancer-focused resources as a foundation for future effective development and application of state-of-the-art bioinformatics tools for multiomic data integration.

A Boolean-algebraic framework for maximal-degree U-k-seminets is presented, unifying combinatorial and algebraic properties. This work extends Aczel’s quasigroup theory and Belousov’s k-net constructions by introducing a computational framework for U-k-seminets of maximal degree µ. Key results include: (1) explicit bounds for µ in terms of set cardinality t and t-order d (µ = t−d+2), (2) existence conditions for nonequipotent sets, and (3) inequalities governing µ and t ((t+2)/2 < µ ≤ t). Theorems are validated via tabulated solutions for m = t−d, demonstrating scalable applications in finite geometry and network design. The framework bridges partial quasigroups and block designs, offering algorithmic tools for seminets with maximal degree constraints.

CNS infections represent a unique challenge to clinicians due to significant morbidity and mortality. The role of ferritin as a reactant of various pathological conditions is currently being intensively investigated. The pathogenesis of cognitive impairment after acute neuroinfectious disease is not yet fully understood. It is believed to be a direct consequence of neuronal damage by the infection, but also by the activation of immunocompetent brain cells, with consequent disruption of signal conduction in a varying period of time after the infection has resolved. The aim of the study is to examine the prediction of ferritin on the degree of cognitive impairment in patients who have suffered from a CNS infection. The values of CSF ferritin were evaluated in three analyzed groups of subjects (bacterial, viral and group with normal CSF findings - meningism). The analyzed clinical data were correlated with the degree of neurocognitive impairment, and the relationship between CSF ferritin and the degree of cognitive impairment was analyzed. The conducted research is a retrospective-prospective analytical and clinical study that was conducted in the period from 01.01.2017 to 01.01.2020. The research includes 90 patients according to previously nominated criteria, divided into three groups, two “examined” and one “control”. The assessment of the cognitive status of the subjects was performed using the MMSE test. The SPSS for Windows software package (version 20.0, SPSS INC, Chicago, Illinois, USA) was used for statistical analysis of the obtained data. We confirmed that the CSF protein ferritin is a good predictor of distinguishing purulent from viral meningitis / meningoencephalitis. The obtained results did not confirm the hypothesis that elevated CSF ferritin values have a negative impact on cognition. Impairment of individual domains of cognition measured by MMSE I, such as “attention”, “calculation” and “memory” are more pronounced in purulent CNS infections. Impairment of individual domain MMSE II “calculation” is more pronounced in the purulent CNS infection category

This article questions the extraterritorial scope of the Digital Markets Act (DMA) in relation to the Western Balkans. We argue that the complex interplay between the requirement to adopt the DMA as part of the European Union (EU) accession process and the region’s limited capacity to enforce it may harm competition and consumer welfare. Moreover, it could diminish the EU’s appeal in the region. Given the potential lack of beneficial effects even after formal adoption, countries in the Western Balkans may turn to alternative regulatory models for digital market competition. These developments raise concerns about the effectiveness of the EU’s digital regulatory agenda beyond its borders. In response, we propose that the EU reassess the DMA’s extraterritorial reach to support better adoption and enforcement in the Western Balkans. A more tailored approach could help ensure that the DMA achieves its goals without producing unintended negative consequences in candidate countries.