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A number of studies have investigated whether cross-modal correspondence effect occurs in purely automatic manner or whether top-down processes can be involved in the processing. The current study addresses the disparity in the research conducting two experiments, using a classical audiovisual cross-modal correspondence paradigm and testing possible involvement of the endogenous component in the effect. Experiment 1 replicated previous findings and showed presence of cross-modal correspondence between pitch and spatial position. However, the effect was significant only in upper spatial position. Experiment 2 showed that task-related pitch probability manipulation made the cross-modal correspondence effect to disappear, however revealing an asymmetrical pattern that was highly dependent on pitch probability and spatial position. Overall, the results suggested a non-automaticity of the cross-modal correspondence effect and a possible involvement of endogenous component in the effect.

The individual approach in the treatment of heart failure (HF) and personalized medicine have been the main topic in recent years in all scientific forums. The combination of chronic obstructive pulmonary disease (COPD) and sleep apnea (SA) further complicates the clinical presentation in patients with HF. The overlap of all three diseases requires a team of specialists and additional therapeutic approach for better control and to improve the prognosis. A large number of the pathophysiological mechanisms of the three diseases also overlap. The novel therapies for HF have shown good results, both in COPD and CA subgroups. Noninvasive ventilation during hospitalization and at home is an established method in the individual groups. In a combination of the three diseases, definitive data from randomized trials are still lacking.

This study analyses the relationships between economic development, environmental investments, and greenhouse gas emissions in the European Union for the period 2008-2022. Using correlation and regression analysis of data from Eurostat, the study assesses the impact of environmental protection expenditure and gross domestic product on greenhouse gas emissions. The results reveal a stable upward trend in environmental protection expenditure, especially in recent years, reflecting the European Union's growing commitment to sustainable development. At the same time, greenhouse gas emissions show an overall downward trend, with the sharpest decline between 2019 and 2020, likely due to the impact of the coronavirus disease pandemic. The correlation analysis confirms a significant inverse relationship between environmental investments and emissions, demonstrating the positive effect of "green" spending on reducing the carbon footprint. An important observation is that in many years, environmental expenditure grows at a faster rate than the European Union's gross domestic product, emphasizing the increased commitment to environmental issues even in conditions of economic growth. The regression analysis shows a strong relationship between the predictors (gross domestic product and environmental expenditure) and greenhouse gas emissions. Despite the expectation that economic growth would increase emissions, the results show that effective measures and technologies for reducing the carbon footprint in the European Union mitigate this effect. Based on these findings, the study proposes strategies for promoting investments in clean technologies, integrating environmental goals into economic policies, intensifying research and innovation, raising public awareness, and strengthening international cooperation.

Human peripheral blood mononuclear cells (PBMCs) are used to examine biological processes and disease, when basal variability in cellular activation and splicing is described and unexplained. Using isolation systems that maintained buffy coat cells (PBMCs, platelets) in their own plasma, poly-A enriched RNA-sequencing (RNASeq) detected 42,720 Ensembl gene IDs, including >95% of the top 100 Genotype Tissue Expression Project (GTEx)-expressed genes in lung, colon, heart, skeletal muscle and liver, and 10/17 clinically-actionable genes listed by the Pharmacogenomics Knowledgebase. Transcriptome changes were defined after 1h treatment with 32°C hypothermia (hsp70 family member change), 10 μmol/L ferric citrate that had no discernible effect, and 100 μg/mL cycloheximide leading to induction of primary response (immediate early) genes including IL1B and TNF. Same-donor PBMCs prepared conventionally using washes then resuspension in serum-supplemented media demonstrated basal upregulation of stress signalling pathway genes that masked and overlapped differential gene expression profiles after 100 µg/L cycloheximide. Plasma-resuspended PBMCs demonstrated minor transcriptome changes after 40 μmol/L ferric citrate, whereas consistent and greater magnitude changes were observed for washed/media-resuspended PBMCs. We conclude that endogenous plasma-maintained PBMCs provide a more robust platform to interrogate acute cellular perturbations triggering innate immunity, and that varying susceptibility of PBMCs to preparative stresses is an important component of experimental variability.

Betulinic acid (BA) is a natural pentacyclic triterpenoid with significant pharmaceutical potential. We found that converting BA into amino acid ethyl ester salts alters its cytotoxic effect on colorectal adenocarcinoma cells (HT-29). Among these salts, the estimated half-maximal inhibitory concentration (IC50) at 72 h varies by up to fifteenfold. The proline ethyl ester [ProOEt] salt, the most active compound, exhibited an IC50 value of 3.8 µM, which is 4.8 times lower than that of the parent BA. We observed that exposure to BA or [ProOEt][BA] induced apoptosis in HT-29 cells. Additionally, the proline-based salt led to a higher level of IL1B gene expression in PBMCs at a lower stimulation concentration.

This study analyses the relationship between economic growth, measured by gross value added in agriculture, and greenhouse gas emissions from the sector in 30 European countries during the period 2012–2021. The aim is to assess whether the increase in agricultural production leads to a corresponding increase in harmful emissions. Regression analysis is applied to establish linear statistical dependencies between variables, cluster analysis to group countries, and analysis of trends in the dynamics of indicators. The results show significant differences between countries, with no universal relationship between economic growth and emissions. A “decoupling” between growth and emissions is observed in some countries, demonstrating the potential for “green growth.” Regional and structural differences, as well as the level of technological development, stand out as key factors determining the relationship between economic growth and emissions, highlighting the need for an individualised approach in formulating policies for the sustainable development of the agricultural sector.

The pathogenesis of many diseases, such as obesity, depression, cancer, cataract, and neurodegenerative diseases, is related to the generation of reactive oxygen species (ROS). Structures possessing radical-scavenging properties act as antioxidants and they could prevent the progression of the aforementioned diseases. Therefore, the current work was focused on the resynthesis and the antioxidant evaluation of 13 hydrazide-hydrazones. Two in vitro tests - DPPH and ABTS, were applied for the determination of the antioxidant capacities. The free-radical scavenging assays displayed that the hydrazide-hydrazone synthesized after condensation with a salicylaldehyde (5b) is the most potent antioxidant. The in vitro evaluation through the ABTS test showed that the former structure has greater antioxidant properties compared with the used standard - Trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). In concentrations of 31 µM, the pyrrole-based structure showed 35.77% radical-scavenging effects. A possible binding conformation of the most active hydrazide-hydrazone in the active site of NADPH oxidase was visualised through docking simulations. The active amino acids involved in the stabilisation of the complexes were discussed. DFT studies demonstrated that 5b is a stable structure with good hydrogen and electron donating properties. Overall, the pyrrole-based hydrazide-hydrazone possesses promising antioxidant properties, however further in vitro/in vivo biological evaluations are required.

Abstract Background Around 60% of term labours in the UK are continuously monitored using cardiotocography (CTG) to guide clinical labour management. Interpreting the CTG trace is challenging, leading to some babies suffering adverse outcomes and others unnecessary expedited deliveries. A new data driven computerised tool combining multiple clinical risk factors with CTG data (attentive CTG) was developed to help identify term babies at risk of severe compromise during labour. This paper presents an early health economic model exploring its potential cost-effectiveness. Methods The model compared attentive CTG and usual care with usual care alone and simulated clinical events, healthcare costs, and infant quality-adjusted life years over 18 years. It was populated using data from a cohort of term pregnancies, the literature, and administrative datasets. Attentive CTG effectiveness was projected through improved monitoring sensitivity/specificity and potential reductions in numbers of severely compromised infants. Scenario analyses explored the impact of including litigation costs. Results Nationally, attentive CTG could potentially avoid 10,000 unnecessary alerts in labour and 2400 emergency C-section deliveries through improved specificity. A reduction of 21 intrapartum stillbirths amongst severely compromised infants was also predicted with improved sensitivity. Attentive CTG could potentially lead to cost savings and health gains with a probability of being cost-effective at £25,000 per QALY ranging from 70 to 95%. Potential exists for further cost savings if litigation costs are included. Conclusions Attentive CTG could offer a cost-effective use of healthcare resources. Prospective patient-level studies are needed to formally evaluate its effectiveness and economic impact in routine clinical practice.

The endophytic fungus Biscogniauxia mediterranea, a causal agent of charcoal canker disease, was established for the first time on red oak (Quercus rubra) in Bulgaria. Symptomatic trees were found in 2023-2024 in the field protective forest belts planted in the State Hunting Enterprise Balchik (Sokolovo and Trigortsi villages) and State Forest Enterprise Dobrich (Kozloduytsi Village) in northeastern Bulgaria. Water stress during the last growing seasons seems to reduce red oak trees’ resistance and predispose them to be infected with the pathogen B. mediterranea. The disease has caused dieback of infected trees and increased their vulnerability to attacks by xylophagous insect pests.

We conducted a Pubmed/Medline database survey of ethical decision-making models in medical practice and health care.

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a new Bulgarian strain of the green microalga Coelastrella sp. BGV were investigated. A fast and convenient method of precipitation with cold ethanol was used to isolate EPS from the culture medium. The chemical characteristics of the isolated EPS were examined by colorimetric and spectrophotometric analyses, HPSEC-RID and HPLC-UV chromatography, and FT-IR spectroscopy. The results showed that the isolated EPS sample consists of three carbohydrate fractions with different molecular weights (11.5 × 104 Da, 30.7 × 104 Da, and 72.4 × 104 Da, respectively) and contains 7.14 (w/w%) protein. HPLC-UV analysis revealed the presence of galactose and fucose. The total uronic acid content in the sample was 4.5 (w/w%). The IR-FT spectrum of EPS revealed the presence of various functional groups typical of a polysaccharide (or proteoglycan) composed primarily of neutral sugars. The anticancer potential of the obtained EPS was assessed using cell lines with cancerous and non-cancerous origins as in vitro experimental models. The results of the performed MTT assay showed that EPS reduced the viability of the cervical and mammary carcinoma cell lines HeLa and MCF-7, while the control non-cancer cell lines BALB/3T3 and HaCaT were less affected. The HeLa cell line showed the highest sensitivity to the effects of EPS and was therefore used for further studies of its anticancer potential. The ability of EPS to inhibit cancer cell migration was demonstrated by wound-healing (scratch) assay. The cell cycle FACS analysis indicated that the EPS treatment induced significant increases in the sub G1 cell population and decreases of the percentages of cells in the G1, S, and G2-M phases, compared to the control. The fluorescent microscopy studies performed using three different staining methods in combination with Annexin V-FITC flow cytometric analysis clearly demonstrate the ability of EPS to induce cancer cell death via the apoptosis pathway. Moreover, an altered pattern and intensity of the immunocytochemical staining for the apoptosis- and proliferation-related proteins p53, bcl2, and Ki67 was detected in EPS-treated HeLa cancer cells as compared to the untreated controls. The obtained results characterize the new local strain of green microalgae Coelastrella sp. BGV as a producer of EPS with selective antitumor activity and provide an opportunity for further studies of its pharmacological and biotechnological potential.

Alzheimer’s disease is a brain disorder characterized by a gradual decline in memory, thinking, behavior, and social skills. Galantamine hydrobromide is a reversible competitive cholinesterase inhibitor used for managing Alzheimer’s disease. Its oral administration, however, is accompanied by unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. These side effects could be avoided by the incorporation of galantamine into nanoparticles. The present study describes the preparation and characterization of HPMC-based fast-dissolving oral films with galantamine-loaded chitosan nanoparticles. Galantamine-loaded chitosan nanoparticles were prepared using the ionotropic gelation method. High values for loading efficiency were established. DLS was used to evaluate the particle size and the Z-potential. The polymer used in this study for the preparation of the fast-dissolving oral films was HPMC, and PEG 400 was used as a plasticizer. The quality of the prepared films was evaluated based on the following criteria: flexibility, spreading ability, adhesiveness, non-sticky and easily peeled, and appearance. The thickness, folding endurance, and disintegration times of the prepared films were determined. In vitro dissolution studies were conducted in order to establish the drug release rate from the films.

We present a clinical case of a 20-year-old woman with acute myocardial infarction with persistent ST-segment elevation (STEMI). The coronary angiography performed on the patient showed coronary vasospasm with no evidence of atherosclerotic plaque. The aim of this case report is to draw attention to the different types of myocardial infarction, other possible differential diagnoses (DD), and to the investigations necessary for determining a definitive diagnosis.

Lactobacilli are considered important probiotics for the prevention of some infections. In this study, the antifungal effect of both cells and cell-free supernatants of twenty-three strains of lactobacilli were investigated against Candida albicans by co-aggregation, agar diffusion assay, agar spot assay and co-culture assay. In all cases, a fungistatic effect was recorded. In the agar diffusion assay and agar spot assay, an effect was established primarily for heterofermentative species via the production of lactic acid. The anti-Candida effect was higher with microbial suspension than with cultural supernatants in the co-culture assay. A strain-specific reduction in the yeast growth up to 28.9% in MRS broth and up to 17.1% in BHI broth was observed. Cells of Limosilactobacillus fermentum LLF-01 and Limosilactobacillus reuteri LLR-K67 showed the highest activity in both model systems. For all strains, a lower reduction up to 9.7% was recorded with cultural supernatants. L. fermentum LLF-01 showed the highest ability of co-aggregation (64.8%) with C. albicans, followed by Lactobacillus acidophilus LLA-01, Lactobacillus gasseri LLG-V74, Lactobacillus delbrueckii subsp. bulgaricus LLB-02 and two strains of Lactobacillus delbrueckii subsp. lactis LLL-14 and LLL-F18. The present study showed the potential of several strains of lactobacilli to affect the population of C. albicans in vitro. The combination of cultures with proved anti-Candida and co-aggregation activity in a probiotic formula may have a positive effect for the prevention of yeast overgrowth in the gut and hence for the suppression of candidiasis.

During the period 2019-2020, parasitoids of invasive oak lace bug (Corythucha arcuata) were studied in Bulgaria. Biological material (larvae of C. arcuata) was collected from European oak (Quercus robur) or Austrian oak (Quercus cerris) in five localities of the country. Five eulophid specimens (Hymenoptera: Eulophidae) were reared from the host larvae: Tamarixia pubescens, Elasmus sp., Minotetrastichus sp., Pnigalio sp. and Sympiesis sp. The impact of the parasitoids on the host number was very low (0.1-0.3%). The present records in Bulgaria are the first documented case of adaptation of native parasitoids to the host in the newly occupied areas in Europe and Asia.

In this study, the effects of defoliation caused by fungal pathogens on the tree vitality and growth of a 33-year old Douglas-fir (Pseudotsuga menziesii) provenance plantation in northwestern Bulgaria was presented. The results of the conducted surveys in 2011 and 2020 showed that there were significant differences between the individual provenances of Douglas-fir concerning their susceptibility to the needle cast diseases, caused by the fungal pathogens Rhabdocline pseudotsugae and Phaeucryptopus gaeumannii. The extent of damage, expressed as the amount of Douglas-fir needles cast, varied among provenance groups in individual years. A serious degree of defoliation was assessed among all continental provenances. In 2011, all examined trees from the group of continental provenances had severe symptoms of the needle cast disease. In 71.5% of them, the defoliation of the crowns was over 25% – moderately to severely affected. The average degree of defoliation varied from 18.3% (32 Wаrm Springs) to 89.3% (55 Alamogordo). In 2020, severe defoliation was found among all continental provenances. Both fungal pathogens were found as causes of the defoliation of 64.3% of the trees. The growth indicators: average height, average diameter at breast height, average height- and diameter increment for survived provenances in 2011 (at age 24) and 2020 (at age 33) were evaluated. The loss of needles and the reduced physiological function of the trees affected their vitality in the following years. Relationships between the average current annual height and diameter increment by provenance groups for 2003–2011 and 2011–2020 were calculated. It was found that with an increase in the degree of defoliation, the height and diameter increment of the provenances decreases.