Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

Aggressive angiomyxoma (AAM) is a rare and benign mesenchymal tumor, localized predominantly in the female pelvis. Its invasive growth and local recurrence are challenging for professionals. Histologically, AAM is a tumor with a myxoid, highly vascularized stroma. The diagnosis is made relatively late due to nonspecific symptoms. Treatment of AAM is extensive local surgical excision. Gonadotropin-releasing hormone agonists are added postoperatively. The prognosis is good and metastasis is rare. We present a case of an AAM located in the left greater labial area in a 50-year-old woman initially diagnosed as left inguinal hernia. The tumor was extirpated under epidural anaesthesia on the date of the patient's informed consent. The patient was prescribed postoperative therapy with Zoladex 3,6 mg according to the schedule. The patient was subjected to monthly gynecological check-ups for one year after the surgical intervention. To date, no recurrence of the underlying disease has been detected. Long-term results show a good trend. In conclusion, we can say that the optimal treatment of AAM is wide local excision. Рadicality is not recommended because of the risk of postoperative complications. Postoperative administration of GnRH-a is advisable to avoid recurrences. All patients undergo regular follow-up examinations for long-term.

Endometriosis is an oestrogen-dependant reproductive disease, with genetic, vascular, neural, inflammatory and auto-immune characteristics. There are many theories about the etiology of endometriosis, however, all of these theories have limitations and do not explain all the locations that endometriosis is found or types of patients with endometriosis. The objective of this paper is to postulate the hypothesis that endometriosis is caused by Maternal Microchimerism, the presence of maternal cells in the fetus. A literature review was conducted, analysing the characteristics, current etiological theories of endometriosis, theory limitations and relationship of maternal microchimerism and endometriosis. At time of writing, there was no literature on maternal microchimerism and endometriosis. These results suggest that Maternal Microchimerism could be a cause of endometriosis. This could account for the genetic and auto-immune characteristics seen in people with endometriosis, inducing a micro-environment for vascular, neural and epigenetic changes. This could also account for account for endometriosis seen in non-menstruating patients, such as men, fetuses and post-menopausal women and endometriosis found in non-peritoneal locations. If the hypothesis of Maternal Microchimerism is correct, endometriosis could be considered a pregnancy-related disease that could affect all humans, changing the accepted demographics of patients and potentially new diagnostic techniques and treatment options for patients with endometriosis. Further studies are needed to test this hypothesis.

Green finance in the context of sustainable development sits within the broader discourse of environmental economics and sustainable finance. Their integration has become imperative in addressing global challenges, aiming to understand how financial mechanisms can be aligned with sustainability goals, investigating the role of green finance in promoting environmentally friendly investments and fostering sustainable development. This bibliometric analysis explores the evolution, trends, and challenges in green finance research. It examines 436 articles published between 2016 and 2024, revealing insights into influential publications, authors, journals, institutions, and countries engaged in green finance for sustainability. The study identifies China, the UK, and Pakistan as leaders in research output and citation impact. Furthermore, it highlights the interdisciplinary nature of green finance, reflected in diverse publication outlets spanning environmental, social, and economic domains. The analysis underscores the increasing global interest in green finance, as evidenced by the growing citation rates over time. Key findings include the pivotal role of green finance in energy efficiency, renewable energy development, and the promotion of sustainable economic growth. Overall, this research provides valuable insights for policymakers, researchers, and practitioners, emphasizing the importance of interdisciplinary collaboration and continued research efforts in advancing sustainable finance agendas.

Antioxidants reduce arterial stiffness but the effects previously reported are weak. The present study evaluated the effects of 2 weeks of therapy with a combination of antioxidants (l-cysteine, thiamine, pyridoxine and ascorbic acid) compared to placebo on stiffness index (SI) a measure of arterial stiffness that is strongly correlated with central pulse wave velocity (PWV), using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by 1.7 m/sec relative to placebo (95% confidence intervals 0.6 to 2.7 m/sec), a reduction of 19% (95% confidence intervals 9% to 31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than found in previous studies of the effects of antioxidant therapy on arterial stiffness. The magnitude of reduction in SI was positively correlated with increasing age (r = 0.362 P = 0.02). The change in RI, a measure of compliance of small to medium size arteries, did not differ between the antioxidant and placebo groups The combination of antioxidants studied reduced PWV to a much greater extent than reported for other antioxidants. This combination may be of value in the treatment of cardiovascular disease.

Tracking temperature changes in certain geographic regions is a current task in modern research on Earth's climate changes. One of the global problems in solving this task is related to the large volume of measured data and the search for appropriate methods for effective determination of changes. The purpose of this research is to track climate temperature changes using a machine learning-based automated change detection method. The presented method includes training of a two-level structure of neural networks, with measured temperatures for a ten-year period of time for a certain geographical region. In the testing phase, the neural structure classifies measured temperatures for two three-year periods, before and after the ten-year time period, respectively, for the same geographic region. An algorithm was developed to visualize the studied regions by creating a map with their geographic coordinates. The classification results in the neural structure outputs are presented and analyzed as possible temperature changes. Suggestions for continuing and expanding the research in the future are discussed.

. Identifying students who might have difficulty in their course of studies ahead of time is crucial. There can be many reasons for performance issues, such as personality, family, social, and/or economic. We advocate that educational systems should use machine learning to predict students’ performance based on performance factors. This would allow educational professionals and institutions to put in place a preventive plan to help students towards achievements of their educational goals and success. In this chapter, we propose a student performance prediction method and evaluate its performance. We provide a taxonomy of performance factors that help to gauge students performance from different perspectives and give insights on the categories and features that have more significant impact on students’ performance. The results of this work can be used by education institutions to put in place a student-centric approach to tackle performance issues before they create long-term effects on student’s life. In addition, it will help education policymakers to introduce a tailored approach for the population in specific areas.

During the last few decades, the main focus of numerus studies has been on the human breast milk microbiota and its influence on the infant intestinal microbiota and overall health. The presence of lactic acid bacteria in breast milk affects both the quantitative and qualitative composition of the infant gut microbiota. The aim of this study was to assess the dominant cultivable rod-shaped lactic acid bacteria, specific for breast milk of healthy Bulgarian women and fecal samples of their infants over the first month of life, in 14 mother-infant tandem pairs. Additionally, we evaluated strain diversity among the dominant newly isolated species. 68 gram-positive and catalase negative strains were subjected to identification by using MALDI-TOF technique. Predominant culturable populations belonging to the rod-shaped lactic acid bacteria have been identified as Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, Lacticaseibacillus paracasei and Limosilactobacillus reuteri. Also, we confirmed the presence of Lactiplantibacillus plantarum and Lactobacillus gasseri. 27 isolates were selected as representatives and analyzed by 16S rDNA sequencing for strain identity confirmation and a phylogenetic tree based on 16S rDNA gene sequence was constructed. Comparative analysis by four RAPD primers revealed genetic differences between newly isolated L. rhamnosus strains. This pilot study provides data for the current first report concerning investigation on characteristic microbiota of human breast milk and infant feces in Bulgaria.

With increasing interest in the use of additive manufacturing techniques in the construction industry, static rheological properties of fresh concrete have necessarily come into focus. In particular, the knowledge and control of static yield stress (SYS) and its development over time are crucial for mastering formwork-free construction, e.g. by means of layered extrusion. Furthermore, solid understanding of the influences of various concrete constituents on the initial SYS of the mixture and the structural build-up rate is required for purposeful material design. This contribution is concentrated on the effect of aggregates on these rheological parameters. The volume fraction of aggregates was varied in the range of 35 to 55 % by volume under condition of constant total surface area of the particles. The total surface area per unit volume of cement paste was equal to 5.00, 7.25 and 10.00 m²/l, conditioned on the constant volume fraction of aggregates. Both variations were enabled by changing the particle size distributions of the aggregates while holding the cement paste composition constant for all concrete mixtures. To characterise the SYS and the structural build-up, constant shear rate tests with a vane-geometry rotational rheometer were performed. It was found that in the ranges under investigation the variation in volume fraction had a more pronounced effect on the static rheological properties of concrete than did the variation in surface area. An accurate mathematical description of the relationship between the initial SYS of concrete and the relative volume fraction of aggregate based on the Chateau-Ovarlez-Trung model was proposed. Challenges in deriving a similar relationship for the structural build-up rate of concrete were highlighted.

The modern technologies require the need to analyze the opportunities for improvement the integration of digital technologies in CSR activities in the context of added values be-tween business and science in perspective, incl. the future digital society. The main goal of this article is to identify the current state of research on the integration of digital technolo-gies in CSR activities in business, as well as to prepare recommendations for further re-search and practice. A systematic literature review and bibliometric analysis of 129 scien-tific articles published between 2014 to 2023 was performed. The bibliometric analysis was organized in two directions: descriptive and performance analysis, through which we can study the contribution of the analyzed objects to the given scientific area, and science mapping, which studies the relationships among them. The results indicate that the com-panies use more frequently artificial intelligence, blockchain, the Internet of Things and other technologies to increase the efficiency and impact of their CSR activities. In addition, this research reveals the basis of bringing forward the new trends for future publications, which shall upgrade and enrich the theory and practice.

With climate change projected to increase the frequency and severity of episodic insect outbreak events, assessing potential consequences for soil microbial communities and nutrient dynamics is of importance for understanding forest resilience. The forest tent caterpillar (Malacosoma disstria) is an important defoliator of deciduous tree species in temperate and mixed forests of eastern North America with an invasion cycle every 10-12 years and outbreak events that can last 3-6 years. Following a defoliation episode on trembling aspen (Populus tremuloides) from 2015 to 2017 in Abitibi-Témiscamingue, QC, Canada, we sought to test if defoliation resulted in changes to soil bacterial and fungal communities. We hypothesized an increase in soil microbial biomass due to increased caterpillar frass inputs and potential changes in community structure following the event. Soils were sampled in July 2018, May 2019 and July 2019 from sites that had been subject to defoliation during the outbreak and from sites where no defoliation had been recorded. We assessed soil microbial biomass and fungal to total microbial activity ratio on all sampling dates, and Community Level Physiological Profiles (CLPPs) for 2018 only using a substrate induced respiration method. Contrary to our hypothesis, we observed a significant 50% decrease in microbial biomass (g biomass-C g-1 soil hour-1) in defoliated stands suggesting tree carbon normally allocated towards root exudates was reallocated towards foliage regeneration. We noted a differentiated carbon-based substrate usage following defoliation, but no change in the fungal to total microbial activity ratio. The observed changes in the two years following the defoliation event suggest that defoliation episodes aboveground could trigger changes in soil chemistry belowground with effects on soil microbial communities that may, in turn, feedback to influence forest plant dynamics.

Confusion, fear and mixed sentiments prevail in the minds of people towards what is arguably one of the most important of dynamics of modern human society: Artificial Intelligence (AI). This study aims to explore the contributions of news media towards this phenomenon - we analyze nearly seventy thousand recent news headlines on AI, using natural language processing (NLP) informatics methods, machine learning (ML) and large language models (LLMs) to draw insights and discover dominant themes. Our theoretical framework was derived from extant literature which posits the power of fear producing articles and news headlines which produce significant impacts on public behavior even when available in small quantities. We applied extensive textual informatics methods using word and phrase frequency analytics, sentiment analysis and human experts based thematic analysis to discover insights on AI phobia inducing news headlines. Our rigorous analysis of nearly seventy thousand headlines using multiple validation methods in NLP (exploratory informatics including BERT, Llama 2 and Mistral based topic identification), ML (supervised informatics) and LLMs (neural nets for sentiment classification, with BERT, Llama 2 and Mistral) demonstrates the presence of an unreasonable level of emotional negativity and fear inducing verbiage in AI news headlines. The framing of AI as being dangerous or as being an existential threat to humanity can have a profound impact on public perception, and the resulting AI phobia and confusion in public perceptions are inherently detrimental to the science of AI. Furthermore, this can also impact AI policy and regulations, and harm society. We conclude with a discussion deducing implications for society and make recommendations for education and policies that could support human identity and dignity.

The main goal of the paper is to use a generalized proportional Riemann-Liouville fractional derivative (GPRLFD) to model BAM neural networks and to study some stability properties of the equilibrium. Initially, several properties of the GPRLFD are proved such as the fractional derivative of a squared function. Also some comparison results for GPRLFD are provided. Two types of equilibrium of the BAM model with GPRLFD are defined. In connection with the applied fractional derivative and its singularity at the initial time the Mittag-Leffler exponential stability in time of the equilibrium is introduced and studied. An example is given illustrating the meaning of the equilibrium as well as its stability properties.

The genus Allium L. attracts the attention of researchers due to the presence of valuable medicinal, nutritional and decorative properties, adaptive capabilities, resistance to pests and diseases, ecological plasticity in its representatives, which contributes to the competitiveness of species and the manifestation of a high degree of adaptation outside natural areas and wide geographical distribution. Allium resources in Russia are a potential source of genes for expanding the genetic base of agricultural crops. The leaves of Allium crops have a short freshness period and quickly deteriorate due to spoilage and loss of water. Spoilage and loss of water affect their freshness and properties. The aim of the work was to establish the yield and change in the quality of green leaves of Allium species introduced into the Moscow region during short-term storage, depending on the type of packaging, storage period and temperature. 4-5-year-old plants of 4 species (A. altyncolicum, A. chyatophorum, A. nutans and A. turkestanicum) were grown on the collection plot of perennial onions of VNIIO, a branch of the FGBNU FNTSO. In the conditions of the Moscow region, the yield per leaf generation varied from 2.7 kg/m2 (A. altyncolicum) to 4.9 kg/m2 (A. cyathophorum). The maximum yield of marketable products was noted in hermetically sealed plastic bags when stored for 10 days at a temperature of +6 ... + 80С in a refrigerator with controlled conditions: A. turke-stanicum - 70.0%, A. cyathophorum - 75.5%, A. altyncolicum - 84.9%, A. nutans - 92.9%. However, an increase in the dry matter content (10.1-15.5%) was found during storage in an open polymer box in all tested species. The maximum content of vitamin C during storage in hermetically sealed bags with a density of 100 μm was found in A. altyncolicum (37.1 mg%) and A. nutans (42 mg%). In other species, the maximum value of this indicator was noted before storage. A slight increase in the amount of sugars after storage for 10 days was noted in species with a linear leaf shape when stored in a polymer box. Temperature control is the most effective approach to extend the shelf life of fresh green leaves by measuring its weight loss and vitamin C. Packaging cannot prevent spoilage of vegetables but can protect it against contamination, damage and excessive moisture loss.

Speciation analysis is a relevant topic since the (eco)toxicity, bioavailability, bio (geo)chemical cycles, and mobility of a given element depend on its chemical forms (oxidation state, organic ligands, etc.). Reliability of analytical results for chemical species of elements depends mostly on the maintaining of their stability during sample pretreatment step and on the selectivity of further separation step. Solid phase extraction (SPE) is a matter of choice as most suitable and widely used procedure for both enrichment of chemical species of elements and their separation. Features of sorbent material are of great importance to ensure extraction efficiency from one side and selectivity from other side of SPE procedure. This review presents an update on the application of polymeric materials in solid-phase extraction used in non-chromatographic methods for speciation analysis.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation plays a crucial role as a pathogenetic mechanism in PD. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship be-tween cellular bioenergetics and YKL-40. Materials and methods: The study included 18 naïve PD and an age-matched control group (HC, n=7). Patients were diagnosed according to the MDS-PD, the UPDRS and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD’s patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. Results: New data are reported revealing changes in mito-chondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in the PD compared to HC. The protein levels of YKL-40 were three-fold higher in PD. We found a correlation between YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. Conclusion: These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

Composite timber-concrete constructions are innovative structural systems which have become the subject of research and practical usage, primarily due to their attractive mechanical properties. This article deals with the experimental procedure and the analysis of the mechanical behavior of two different serious of timber-concrete composite beams. In the composite beams of the A series, screws were used as a fastening system in the interlayer between the timber and concrete parts, whereas in the B type series, a more complex system, the combination of notches and screws, was used for the same purpose. Both series were exposed to loading up to a fracture point by the means of the standard procedure (four point bending test). The mechanical behavior of the A and B-series beams was analyzed by a comparative analysis referring to: the correlation of the fracture loading and the deflection at the moment of fracture, forms and mechanisms of fracture, the development of dilatations at certain points of specific cross-sections, the displacement in the timber-concrete interlayer in the support zones, the value of shear stresses and the calculated values of the effective bending stiffness of the beams. The B-series beams where a more complex fastening system, as it was expected, showed a better mechanical behavior than the A-series beams.

Open-pit uranium mining in the south Texas Gulf Coast region was active during the second half of the 20th century. Although some mines have extensive records documenting the locations and extents with descriptions of reclamation procedures and timelines, abandoned and reclaimed mines with minimal documentation concurrently exist where little is known about locations, mine waste volumes, and reclamation status. Advanced mapping of these mining operations is helpful for producing basic mine land inventories and assessments of mine waste; identifying potential undeveloped resources and environmental health issues; and for developing proper management, restoration, and reclamation strategies. We studied known reclaimed and unreclaimed mine sites to develop a spatiotemporal mapping approach utilizing multiple techniques in remote sensing as a proof of concept. A mapping classification system was developed to identify uranium mine waste-rock piles, mine pits (with and without waste water), the total area of land disturbance due to mining, and to differentiate abandoned and reclaimed mine features using lidar (Light Detection and Ranging) analysis and multispectral temporal analysis. Visual interpretation of Landsat imagery and time-series analysis revealed the temporal life-cycle of mining, historical areas of disturbance, and reclamation; however, mine features below vegetation canopies are not always visible in satellite imagery. Lidar laser scanning penetrates the vegetation canopy to measure the topographic elevation and exposes anthropogenic modifications to the landscape. Lidar analysis (bare earth elevation surface, slope, topographic contours, topographic textures, and overland-flow hydrography) revealed mine features, and expansive areas of mining disturbance. The spatiotemporal mapping approach proved to be useful for identifying and characterizing known mine features, areas of disturbance, and reclamation status. Historical pre-mining topographic data were available at only 4 of the mines for comparison where the cut-and-fill tool estimated 21% less waste-rock volume, indicating that information about pre-mining terrain topography and/or subsurface mine waste geometry is needed to improve accuracies for quantifying buried mine waste volume at reclaimed mine sites.

HIV incidence remains alarmingly high among female sex workers (FSWs) in low- and middle-income countries, with Uganda being no exception. The elevated risk of HIV transmission among this vulnerable population can be attributed to a complex interplay of factors, including engaging in sexual activities with multiple partners, inconsistent condom usage, substance use, and structural barriers, such as legal criminalization and pervasive stigmatization by healthcare providers. To combat this epidemic, various HIV prevention interventions have been devised, targeting these multi-faceted challenges. This study involved conducting focus groups among FSWs and healthcare providers in Uganda, with the overarching objective of informing the development of a tailored HIV prevention intervention aimed squarely at FSWs. Through these discussions, valuable insights were gained into FSWs’ perceptions of their HIV risk, their attitudes regarding HIV prevention strategies, and their recommendations regarding the content and delivery of future interventions.

This paper presents a study of human blood sera samples, collected in various regions of the Russian Federation, with regard to both vaccine and pandemic avian influenza viral strains. Just before the 2022-2023 epidemic season, herd immunity to seasonal influenza A viruses was reportedly lower than before the COVID-19 pandemic. Since no stable circulation of A/H5Nx and A/H9N2 influenza in the human population was observed during this period, we believe 100% vaccination against seasonal influenza is necessary for employees of poultry farms and other organizations, closely connected to the breeding and processing of poultry. In addition to protection against seasonal influenza, vaccination can hamper the emergence of new viral variants, driven by genome reassortment, during simultaneous infection of humans with seasonal human and animal influenza viruses.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

This article presents a hybrid approach to assessing students’ foreign language proficiency in a cyber-physical educational environment. It focuses on the advantages of integrated assessment of student knowledge by considering the impact of automatic assessment, learners’ independent work, and their achievements to date. An assessment approach is described using the mathematical theory of fuzzy functions, which are employed to ensure fair evaluation of students. The largest possible number of students, whose re-evaluation of test results will not affect the overall performance of the student group, is automatically determined. The study also models the assessment process in the cyber-physical educational environment through the formal semantics of calculus of context-aware ambients (CCA).

Since certain Mycobacterium tuberculosis complex (MTBC) members, like M. bovis, are endemic in specific South African wildlife reserves and zoos, cases of clinically important nontuberculous mycobacteria (NTM) in wildlife may be neglected. Additionally, due to the inability of tests to differentiate between host responses to MTBC and NTM, the diagnosis of MTBC may be confounded by the presence of NTMs. This may hinder control efforts. These constraints highlight the need for enhanced rapid detection and differentiation methods for MTBC and NTM, especially in high MTBC burden areas. We evaluated the use of the GeneXpert MTB/RIF Ultra, the Hain CMdirect V1.0, and novel amplicon sequencing PCRs targeting the mycobacterial rpoB and ku gene targets, directly on antemortem respiratory samples from known MTBC-infected and NTM culture-positive African elephants (n=26 animals) and rhinoceros (n=23 animals). Our findings suggest that the Ultra is the most sensitive diagnostic test for MTBC DNA detection directly in raw antemortem respiratory specimens and that the rpoB PCR is ideal for Mycobacterium genus DNA detection and species identification through amplicon sequencing.

In this study, we made an estimate of the carbon and nitrogen content in the undisturbed terrestrial ecosystems in the northern taiga zone of Russia’s Murmansk region. The goal of this study was to examine the carbon and nitrogen dynamics in atmospheric fallout, assimilating organs of coniferous trees (Picea obovata and Pinus sylvestris), needle litter, soils, and soil water. The objects of our re-search were the most common dwarf shrub-green moss spruce forests and lichen-dwarf shrub pine forests of the boreal zone. The study was carried out on permanent plots between 1999 and 2020. Long-term dynamics of carbon concentrations in snow demonstrated a trend towards increasing carbon concentrations in forested and treeless areas of Murmansk region. It was shown that in representative spruce and pine forests, the concentrations and atmospheric fallout of carbon compounds and carbon leaching with soil water were higher below the tree crowns, compared to between the crowns. In soil water, a decrease was found in carbon leaching with the soil profile depth. For soils, the highest carbon concentrations were found in the organic and illuvial soil ho-rizons. The main soil sinks of carbon and nitrogen in northern taiga forests were found to be located in the organic soil horizon below the crowns. In northern taiga forests, the carbon content of living Picea obovata and Pinus sylvestris needles and Pinus sylvestris needle litter had minor variability; no significant interbiogeocoenotic and age differences were found. We found that the nitrogen content in brown needles and needle litter was significantly lower compared to photosynthetically active needles.

Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus early diagnosis is crucial for identifying high-risk patients to prevent irreversible complications. Thirty-one patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z- scores of bone mineral density (BMD): In GD cohort with no bone complication (Z-score≥-0.9; T-scores≥-1), the OSN group (-1.8 ≥ Z-score ≥ -1; -2.5 ≥ T-score ≥ -1) and OSR group (Z-score ≤ -1.9; T-scores ≤ -2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. TRAP5b was increased in GD and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (Lyso-Gb1), macrophage activation markers CCL18 and chitotriosidase. The highest levels of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Elevation of TRAP5b, RANKL, and RANKL/OPG indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.

Abstract: Floods can be defined as one of the most frequent and destructive disasters, that cause significant damage to people, while droughts present significant challenges in first place to most vulnerable communities. In consequence, state public policies are essential to manage the risk in the face of both phenomena and contribute to the construction of resilient communities. As a request of the National Water Commission of Mexico (CONAGUA) for the Regional Water Plan (PHR), we designed and applied a methodology based on virtual consultation fora in conjunction with digital survey tools to understand the population's perception of these phenomena. The workshops were organized in the five municipalities of Baja California Sur. Then, we performed an interdisciplinary analysis that combines hydrological considerations with the most critical social, economic, environmental, and law components, applying the PESTEL analysis. The results indicate that there is a clear and widespread awareness that floods and droughts increase the risk to the livelihoods of the population; however, there are deficiencies in different areas, which complicates risk management. Timely information and the inclusion of communities in mitigation and adaptation proposals would allow for achieving more successful cases with the efforts to minimize vulnerabilities and increase the resilience of the population in the face of a changing climate. This must be a collaborative work of the entire society, governmental, social, and private stakeholders.

A new heterocyclic compound, 2-(2,6-diisopropylphenyl)-1-methylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate 1 was obtained from its precursor, N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)acetamide 2, by POCl3-mediated cyclization. For the first time – the tertiary acetamide 2, precursor of 1, was synthesized by using commercially available starting materials. The structure of 1 was unquestionably confirmed by 1H-, 13C-, 2D-NMR-, IR- spectroscopy and mass-spectrometry. Its optical properties were also studied.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

Bimetallic Ni/Cu core-shell and Cu-Ni heterostructural micro- and nanoparticles were prepared using two simple successive reduction procedures. Monometallic Ni and Cu particles were synthesized for comparison. The phase constitutions and morphological features of the particles were studied by means of X-ray diffraction, energy-dispersive X-ray spectroscopy and scanning electron microscopy methods. All the obtained mono- and bimetallic particles were applied as electrocatalysts in the electrohydrogenation of p-nitrophenol (p-NPh). An additional electrochemical reduction of copper cations during the hydrogen saturation of Cu-containing particles was established. Some of the prepared particles exhibited high catalytic activity with an increase in the hydrogenation rate of p-NPh by more than 3 times compared to its electrochemical reduction on the non-activated cathode, and p-NPh conversion yielded the maximum values. The main product of p-NPh electrocatalytic hydrogenation over Ni-Cu particles is p-aminophenol, which is an intermediate in the synthesis of many drugs. p-Aminophenol formation is confirmed by UV-Vis spectra.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins, and Ca2+-linked transporters and voltage-gated channels. These findings suggest that pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss

The climate change is likely to modify the freezing-thawing cycles in soils and surface waters of permafrost-affected and subarctic regions. Yet, the change of solution chemical composition during ice formation and evolution of remaining fluids remain very poorly known. Towards better understanding of dissolved (< 0.45 µm) organic carbon, major and trace elements behavior in permafrost peatland environments, here we performed laboratory freezing of peat leachates, from complete freezing to complete thawing in order to quantify the partitioning of solutes between the aqueous solution and the remaining ice. We hypothesized the existence of two main groups of solutes, behaving conservatively or non-conservatively during freezing depending on their incorporation into the ice or ability to coagulate in the form of insoluble minerals or amorphous materials in the fluid phase. An unexpected result of this work was that, despite sizable degree of element concentration in the remaining fluid and possible coagulation of organic, organo-mineral and inorganic compounds, the freezing and subsequent thawing produced the final concentrations of most solutes which were not drastically different from initial concentrations in starting leachates, prior freezing. This demonstrates high stability of dissolved (< 0.45 µm) OC, Fe, Al and some trace metals to repetitive freezing and thawing of surface waters in permafrost peatlands.

Background: Despite scientific advances, the management of procedural pain in neonates remains suboptimal. Applying adequate therapy to control pain during the neonatal period is a moral and ethical act. In recent decades, ample evidence has accumulated regarding the risks, associated with both untreated pain and the use of more aggressive analgesic therapy. Thus, the emphasis in neonatal clinical practice is on non-aggressive pain management techniques, including homeopathic agents. The efficacy and safety of homeopathic agents for reducing procedural pain in neonates is the subject of the present study. Materials and Methods: Healthy full-term newborn babies with an average age of 72-84 hours were included. They were divided into three study groups: group (A) – not anesthetised, /n= 67/, group (B) – anesthetised with Arnica D30 /n=40/ and group (C)- anesthetised with Sol.Glucose 25% /n=40/. The severity of the pain was assessed using the multimodal - Neonatal Infant Pain Scale (NIPS) and the unimodal - Neonatal Facial Coding System (NFCS) scale. Assessments were done 30s before, 30 seconds after, and 5 minutes after the painful stimulus caused by the heel prick. Heart rate, transcutaneous oxygen saturation, respiratory rate and blood pressure were examined at the same intervals. The results obtained were processed statistically by descriptive analysis and ANOVA at a significance level of p< 0.05. Results: 5 minutes after heel prick both scales showed a statistically significant lower score in those given Arnica D30, compared to those who received Sol.Glucose 25%. When monitoring the physiological indicators, we found a significant increase in the heart rate 30 seconds after the procedure.5 minutes after the heel prick we recorded significantly respiratory rate and systolic blood pressure in all three groups compared to pre-procedural values. Conclusions: Arnica D30 has better analgesic effects compared to Sol.Glucose 25% for newborn babies after heel prick tests.

According to our previous investigation the total methanol extract from Graptopetalum paraguayense E. Walther demonstrates a significant inhibitory effect on HSV-1. To clarify what causes this inhibitory activity on HSV-1, a metabolic profile of the plant was performed. Three main fractions: non-polar substances, polar metabolites and phenolic compounds were obtained and GC-MS analysis was carried out. Since it is well known that phenolic compounds show a significant anti-herpes effect and that viral DNA polymerase (DNApol) appears to play a key role in HSV virus replication, we present a docking and quantum-chemical analysis of the binding of these compounds to viral DNApol amino acids. Fourteen different phenolic acids found by GS/MS analyses, were used in molecular docking simulations. According to the interaction energies of all fourteen ligands in the DNApol pockets based on docking results, DFT calculations were performed on the five optimally interacting with the receptor acids. It was found that hydroxybenzoic acids from phenolic fraction of Graptopetalum paraguayense E. Walther show a good binding affinity to the amino acids from the active site of the HSV DNApol, but significantly lower than that of acyclovir. The mode of action on virus replication of acyclovir (by DNApol) is different from that of the plant phenolic acids one, probably.

Diagnosis of bovine tuberculosis (bTB) may be confounded by immunological cross-reactivity to Mycobacterium bovis antigens when animals are sensitised by certain nontuberculous mycobacteria (NTMs). Therefore, this study aimed to investigate NTM species diversity in African buffalo (Syncerus caffer) respiratory secretions and tissue samples, using a combination of novel molecular tools. Oronasal swabs were collected opportunistically from 120 immobilised buffaloes in historically bTB-free herds. In addition, bronchoalveolar lavage fluid (BALF; n=10) and tissue samples (n=19) were obtained during post-mortem examination. Mycobacterial species were identified directly from oronasal swab samples using the Xpert MTB/RIF Ultra qPCR (14/120 positive) and GenoType CMdirect (104/120 positive). In addition, all samples underwent mycobacterial culture, and PCRs targeting hsp65 and rpoB were performed. Overall, 55 NTM species were identified in 36 mycobacterial culture-positive swab samples with presence of esat-6 or cfp-10 detected in 20 of 36 isolates. The predominant species were M. avium complex and M. komanii. Nontuberculous mycobacteria were also isolated from 6 of 10 culture-positive BALF and 4 of 19 culture-positive tissue samples. Our findings demonstrate that there is a high diversity of NTMs present in buffaloes, and further investigation should determine their role in confounding bTB diagnosis in this species.

Pediatric brain tumors are the leading cause of cancer-related death in children. Diagnosis cur-rently relies on surgical biopsy to obtain tumor tissue for histological analysis. There is a great need for less invasive approaches to molecularly profile tumors and monitor therapeutic response. Liquid biopsy analysis of circulating tumor biomarkers in biofluids like cerebrospinal fluid (CSF) and blood offers a promising minimally invasive strategy. This review discusses recent advances in developing liquid biopsy assays using next-generation sequencing, digital PCR, and emerging techniques to detect circulating tumor DNA (ctDNA), cells (CTCs), and exosomes in pediatric brain tumors. The ability to use these circulating biomarkers for non-invasive diagnosis, thera-peutic targeting, tracking response to therapy, and understanding resistance mechanisms is ex-amined. Technical and clinical validation challenges to translate liquid biopsies into routine clin-ical practice are also discussed.

This paper presents a comparison between indirect methods for assessing the buildability of 3D printed cementitious materials, including CRV or CSR test using rotational rheometry, unconfined uniaxial compression test (UUCT), a newly proposed confined uniaxial compression test (CUCT), and fast penetration test. The experimental program was conducted on the extruded samples of six printable mortars and two printable concretes with various rheological behavior achieved by the use of different additives and admixtures. Predictions of the material failure and the stability failure in hollow cylindrical structures are provided and compared with the results of the direct printing test. Benefits and disadvantages of the employed test methods are discussed, also taking into consideration a perspective of their use for automated in-situ control of the materials’ buildability.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

Glycerol has found its applications as a heat-transfer fluid in heat exchangers, and as a compo-nent of functional solutions in biosensor analysis. Flowing non-aqueous fluids are known to be able to induce electromagnetic fields due to triboelectric effect. These triboelectrically generated electromagnetic fields can affect biological macromolecules. Horseradish peroxidase (HRP) is widely employed as a convenient model object for studying how external electric, magnetic, and electromagnetic fields affect enzymes. Herein, we have studied whether the flow of glycerol in a ground-shielded cylindrical coil affects the HRP enzyme incubated at a 2 cm distance near the coil’s side. Atomic force microscopy (AFM) has been employed in order to study the effect of glycerol flow on HRP at the nanoscale. Increased aggregation of HRP on mica has been observed after the incubation of the enzyme near the coil. Moreover, the enzymatic activity of HRP has also been affected. The results reported can find their application in biotechnology, food technology and life sciences application, considering the development of triboelectric generators, en-zyme-based biosensors and bioreactors with surface-immobilized enzymes. Our data can also be of interest for scientists studying triboelectric phenomena.

Insect outbreaks are major drivers of natural disturbances in forest ecosystems. Outbreaks can have both direct and indirect effects on the composition of soil arthropod communities, through canopy opening, nutrient addition and predator-prey interactions. In this study, we aim to understand the effects of forest tent caterpillar (Malacosoma disstria; FTC) outbreaks on ant communities in both temperate and boreal forests in Canada. Using pitfall traps and Berlese funnels, we compared the ant communities as well as the surrounding arthropod communities between control and outbreak sites in boreal andboreal and temperate forests (in Québec, Canada). Using the Sørensen dissimilarity index, we determined the alpha and beta diversity of the ant community. Other arthropods collected in the traps were counted to evaluate the richness and abundance of potential prey for the ants and other potential predators of the FTC. We used an indicator species analysis to examine the species associated with sites defoliated by the outbreak. In the boreal forest, we found that FTC outbreaks caused decreases in species richness and increases in the evenness of ant communities in defoliated sites. In the boreal forest sites, species composition varied significantly between control and outbreak sites. This pattern was driven by the presence of other predators. We also saw no changes in beta diversity in the boreal forest but did see a significant decrease in the temperate forest between the outbreak sites and the control sites. A similar, but weaker pattern was observed in the temperate forest. Ant species in the boreal forest tended to exhibit a more marked preference for either control or previously defoliated sites than species in the temperate forest. Our study showed that disturbances like insect outbreaks can drive changes in the ant community. While we saw small effects of outbreaks, manipulation experiments using resource addition could help us validate the mechanisms behind these relationships.

A focussed library of pyridyl and 2-hydroxyphenyl chalcones were synthesized and tested for growth inhibitory activity against Mycobacterium tuberculosis H37Rv, and normal and cancer breast cell lines. Pyridyl chalcones bearing lipophilic A-ring, e.g., dichloro-phenyl- (14), pyrene-1-yl (20)- and biphenyl-4-yl (21) moieties, were found to be the most potent of the series inhibiting the growth of M. tuberculosis H37Rv with IC90 values ranging from 8.9 – 28 µM. Aryl chalcones containing a 3-methoxyphenyl A-ring and either p-Br-phenyl (25) or p-Cl- phenyl (26) B-rings showed an IC90 value of 28 μM. Aryl-chalcones were generally less toxic to HepG2 cells compared to pyridyl-chalcones. Dose-dependent antiproliferative activity against MDA468 cells was observed for trimethoxy-phenyl (16) and anthracene-9-yl (19) pyridyl-chalcones with IC50 values of 0.7 and 0.3 µM, respectively. Docking studies revealed that chalone 20 was predicted to bind to the M. tuberculosis protein tyrosine phosphatases B (PtpB) with higher affinity compared to a previously reported PtpB inhibitor.

Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..

This paper presents a study and implementation of a convolutional neural network to identify and recognize humpback whale specimens from the unique patterns of their tails. Starting from a dataset composed of images of whale tails, all the phases of the process of creation and training of a neural network are detailed – from the analysis and pre-processing of images to the elaboration of predictions, using TensorFlow and Keras frameworks. Other possible alternatives are also explained when it comes to tackling this problem and the complications that have arisen during the process of developing this paper.

Competency frameworks outline the perceived knowledge, skills and other attributes required for professional practice. Competency frameworks have gained in popularity, in part for their ability to inform health professions education, assessment, professional mobility, and other activities. Previous research has shown inadequate reporting within reports describing their development and that may jeopardize their use and application. We aimed to develop a set of minimum criteria that provides guidance to authors (and consumers) in an effort to improve reporting of the development of competency frameworks. The checklist was developed by a 35-member expert panel and a five-member research team following published guidance from the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network. The final checklist contains 20 essential reporting items including guidance on reporting title and abstract, framework development, the development process, testing and funding/conflicts of interest. The intent of the COmpeteNcy FramEwoRk Development in Health Professions (CONFERD-HP) reporting guideline is to help readers (including researchers, educators, regulators, health professionals, and patients) develop a greater understanding of relevant terminology, core concepts, and key items to report for competency framework development in health professions.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections represent major a public health concern and require comprehensive understanding of their genetic make-up. This study investigated the first occurrence of IMP-carrying MDR P. aeruginosa strains from Bulgaria. Whole genome sequencing identified a novel plasmid-mediated blaIMP-100 allele located in a In1300-like integron embedded in a novel putative transposon. Two other closely related chromosomal blaIMP variants IMP-13 and IMP-84 were also detected. The IMP-producers were resistant to last-line drugs including cefiderocol (CFDC) (2 out of 3) and susceptible to colistin. The blaIMP-13/84 cassettes were situated in a In320 integron inserted in a Tn5051-like transposon as previously reported. Lastly, the p47825-IMP plasmid rendered PAO1 transformant resistant to CFDC, suggesting a transferable CFDC resistance. A variety of virulence factors associated with adhesion, antiphagocytosis, iron uptake, quorum-sensing, as well as secretion systems, toxins, and proteases were confirmed, suggesting significant pathogenic potential consistent with the observed strong biofilm formation. Emergence of IMP-producing MDR P. aeruginosa is alarming as they remain unsusceptible even to last geneneration drugs like CFDC. Newly detected IMP-100 was even located in an CFDC-resistant XDR strain.

The primary objective of this study is to synthesize, elucidate the structural properties, and ex-plore the biological activity of novel metal complexes derived from 6-methyl-2-thiouracil and 6-propyl-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activ-ity of newly formed Cu(II) and Pd(II) complexes with two substituted 2-thiouracil ligands. The structural attributes of these newly developed compounds are thoroughly discussed based on data derived from melting point analysis, MP-AES for Cu and Pd, UV-Vis, IR, ATR, 1H NMR, 13C NMR and Raman spectroscopy. The interpretation of the complex spectra is assisted by the data for 6-methyl-2-thiouracil and 6-propyl-2-thiouracil obtained from 1H-1H COSY, DEPT-135, HMBC and HMQC spectra. In addition, the antimicrobial activity of these complexes and the free ligands are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Estrogens play a protective role during early life stages. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression in low-grade inflammatory conditions like established atherosclerosis. Our single-center cohort study assessed sex-specific associations of gonadal hormones with oxidative stress, inflammation, and myocardial injury markers in 111 patients (37% women) diagnosed with acute myocardial infarction (MI) between July 2011 and December 2013. Blood samples were collected within 48 hours of symptom onset, and we measured sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitive C-reactive protein (CRP), white blood cell counts (WBC), and cardiac enzymes (creatine kinase [CK], the CK Muscle-Brain fraction [CK-MB], and high-sensitive troponin T [hsTnT]). The SYNTAX score gauged coronary disease severity from coronary angiography results. In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels (OR 1.011, p=0.047 - CK; OR 1.018, p=0.013 - CK- MB; OR 1.019, p=0.005 - TnT), peak WBC count (OR 1.487, p=0.015 - CK ; OR 1,709, p=0,005 - CK- MB; OR 1.391, p=0.012 - TnT), and peak CRP plasma levels (OR 1.040, p=0.033 - CK; OR 1.024, p=0.029 - CK-MB; OR 1.063, p=0.006 - TnT). T levels and E2/T ratio were associated with post-PCI CRP in these men (OR 0.980, p = 0.024 - T, OR 1.010, p = 0.076 - CRP). For women, peak WBC was a marker of highest testosterone (OR 1.348, p = 0.062), and only WBC was a significant indicator of myocardial injury extent (OR 1.426, p=0.039 - CK; OR 1.384, p=0.036 - CK-MB; OR 1.299, p=0.048 - TnT). During acute MI, elevated endogenous estradiol levels correlate with myocardial necrosis severity in men, while in women, increased leukocyte levels indicate acute myocardial damage. Elevated plasma T is associated with increased WBC in women. In men, post-PCI plasma CRP specifically indicates endogenous T levels and E2/T ratio during the acute phase.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

The current research is focused on the discovery and optimization of an effective cosmetic carrier of alpha-bisabolol as a first step in the development of a cosmetic product with cleansing and antimicrobial action for facial skin hygiene. A micellar solution of Poloxamer 407 was selected as a cosmetic base because of the good washing ability, easy application, and high tolerability of this polymeric surfactant. The solubilization capacity of a 5% micellar solution with respect to α-bisabolol was investigated by applying varying solubilization techniques and increasing concentrations of the oily active substance. The test samples were subjected to an accelerated physical stability test, viscosimetry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), foamability test, and antimicrobial screening. In the course of research, the advantage of the film-hydration method over direct solubilization was demonstrated by the narrower size distribution and smaller hydrodynamic size of the micellar nano-carriers (ranging from 29.02-116.5 nm) and the respective higher physical stability of the dispersions. The optimized composition was found to possess a suitable for application on large skin areas viscosity in the temperature range from 20°C to 40°C (3.4-2.3 mPa.s). Preservation of the washing capacity of the micellar solution in the presence of solubilized α-bisabolol was established. The active composition demonstrated inhibitory activity against Staphylococcus aureus and Escherichia coli, and fungicidal activity against Candida albicans. The study concludes that the optimal concentration of α-bisabolol to be solubilized in a 5% Poloxamer 407 micellar solution by the film-hydration technique is 1% considering the desirable physical endurance and antimicrobial activity.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

This paper presents an overview of EREMI, a two-year project funded under ERASMUS+ KA203, and its results. The project team's main objective was to develop and validate an advanced interdisciplinary higher education curriculum, which includes lifelong learning components. The curriculum focuses on enhancing resource efficiency in manufacturing industries and optimizing poorly or non-digitized industrial physical infrastructure systems. The paper also discusses the results of the project, highlighting the successful achievement of its goals. EREMI effectively supports the transition to Industry 5.0 by preparing a common European pool of future experts. Through comprehensive research and collaboration, the project team has designed curriculum that equips students with the necessary skills and knowledge to thrive in the evolving manufacturing landscape. Furthermore, the paper explores the significance of EREMI's contributions to the field, emphasizing the importance of resource efficiency and system optimization in industrial settings. By addressing the challenges posed by under-digitized infrastructure, the project aims to drive sustainable and innovative practices in manufacturing. All five project partner organisations have been actively engaged in offering relevant educational content and framework for decentralised sustainable economic development in regional and national contexts through capacity building at local level. A crucial element of the added value is the new channel for feedback from students. The survey results, which are outlined in the paper, offer valuable insights gathered from students, contributing to the continuous improvement of the project.

The goal of this study is to synthesize, determine the structure, and examine the antimicrobial properties of novel metal complexes of 2,4-dithiouracil and its derivatives. These complexes were obtained by mixing aqueous solutions of the corresponding metal salts with the ligand dissolved in DMSO and aqueous NaOH, using a metal-to-ligand ratio of 1:4:2. The structures of the new compounds were analyzed by melting point determination, microwave plasma atomic emission spectrometry (MP-AES) for Cu and Au, inductively coupled plasma optical emission spectrometry (ICP-OES) for S, ATR, solution and solid-state NMR and Raman spectroscopy. The interpretation of the complex spectra was aided by data for 2,4-dithiouracil obtained from 1H-1H COSY, DEPT-135, HMBC, and HMQC spectra. Additionally, the antimicrobial activity of these complex-es and the free ligands was evaluated against Gram-positive and Gram-negative bacteria, as well as yeasts.

The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer’s, amyotrophic lateral sclerosis (ALS) and Parkinson’s. Platelet-Derived Growth Factor Receptors (PDGFRs) have been shown to be critical to the PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters the PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood-retina barrier (BRB) were evaluated using blood albumin labeling. We found that imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers, this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of imatinib on PCs. Furthermore, the blood-retina barrier disruption was not evident. In conclusion, our data suggest that imatinib could help in treating neurovascular diseases and serve as a model for PC loss, without BRB disruption.

This study explored the potential synergism within chlorhexidine-silver nanoparticles conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively-charged nano-silver colloid (ζ=-50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ=+44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in the effects against S. aureus and C. albicans, and synergism against E. coli with minimal inhibitory concentrations of SN 5.5 µg/mL+Cx 8.8 µg/mL. The SN showed excellent, increasing with time, virucidal properties, and low toxicity. The coupling of the cationic chlorhexidine with nano-silver, however, did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and А549). The newly-synthesized antimicrobial agent presented with an extended and promising therapeutic spectrum and needs to be further evaluated on relevant to the designated route of administration three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

The residual content of the only carbon source increases at the end of the exponential growth phase when P. putida BS3701 cells are cultured under nitrogen deficiency. Moreover, the mRNA quantity of some genes involved in carbon catabolism decreases. There are no available data on regulators capable of stimulating the target mRNA degradation in pseudomonads under nitrogen deficiency in the literature. We have applied both comparative genomics methods and a number of biomolecular ones to identify new small P. putida BS3701 RNAs. This is due to the fact that the formation of ncRNA-mRNA duplexes, recognized by RNases, is one of the main mechanisms for reducing the number of transcripts in a cell. We have used the following selection criteria: 1) the presence of the interest gene of the NtrC binding site and a sigma54-dependent promoter in the upstream area, 2) the conservative location of the interest gene in the P. putida and P. aeruginosa genomes, 3) increase in the product quantity of the interest gene in a cell under nitrogen deficiency on two different carbon sources (succinate and naphthalene), 4) the product detection of the interest gene in a fraction enriched with small RNAs. The expression of two new small RNAs has increased twice or more times under nitrogen deficiency on both succinate and naphthalene: expression of ng171 and ng379. ng379 contains narK RNA motif.

Scavenging of atmospheric trace gases has been recognized as one of the lifestyle-defining capabilities of microorganisms in terrestrial polar ecosystems. Several metagenome-assembled genomes of as-yet-uncultivated methanotrophic bacteria, which consume atmospheric CH4 in these ecosystems, have been retrieved in cultivation-independent studies. In this study, we isolated and characterized a representative of these methanotrophs, strain D3K7, from a subarctic soil of Northern Russia. Strain D3K7 grows on methane and methanol in a wide range of temperatures, between 5 and 30°C. Weak growth was also observed on acetate. The presence of acetate in the culture medium stimulated growth at low CH4 concentrations (~100 p.p.m.v.). The finished genome sequence of strain D3K7 is 4.15 Mb in size and contains about 3700 protein-encoding genes. According to the result of phylogenomic analysis, this bacterium forms a common clade with metagenome-assembled genomes obtained from the active layer of a permafrost thaw gradient in Stordalen Mire, Abisco, Sweeden, and the mineral cryosol at Axel Heiberg Island in the Canadian high Arctic. This clade occupies a phylogenetic position in between characterized Methylocapsa methanotrophs and representatives of the as-yet-uncultivated Upland Soil Cluster Alpha (USCα). As shown by the global distribution analysis, D3K7-like methanotrophs colonize mostly northern terrestrial ecosystems, such as polar deserts, subarctic soils, permafrost environments, but also occur in boreal peatlands or high-latitude habitats.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

3D/4D printing technologies are currently among the fastest growing, cutting edge fabrication technologies. The scale of their applications is vast and applicable to nearly all industries. 3D printing technologies are particularly popular in robotics, and especially in advanced design innovative solutions for areas such as manufacturing, space technology and medicine. The development of robotics, and in particular of the precision of manufactured components, such as actuators, pneumatic muscles, power transmission units, etc., means that new prototypes are still being made, where the use of 3D printers reduces the production time severalfold and allows for completing the necessary simulations and tests. In addition, the use of 3D printers allows for the production of thin-walled and cellular structures, which is a great advantage compared to conventional fabrication technologies. In the range of 3D printers available on the market, only a few selected technologies allow for actual use in the construction of advanced robot elements (muscles, vibration dampers, etc.). In the era of rapid growth of the precision of the available 3D printers and modern materials, 3D printing may soon become a major tool in robotics. This article presents an overview of 3D printing technologies and materials in terms of their application in robotics and provides examples of the use of 3D and 4D printing in prototyping and fabrication of robotic elements with particular emphasis on the current state of the art. The study considered the possibilities of using 3D/4D printing in robotics with the use of polymeric materials. The review of the literature and the research work currently being carried out in this area is very promising and it seems that 3D/4D printing in robotics is widely used and is still developing, which allows to conclude that in the near future the number of research works in this field will increase rapidly.

University students, particularly those in the healthcare disciplines, constitute a category of particular interest in regard to COVID-19 vaccines and the attitudes to vaccination, as their future professional role will enable them to inform and educate citizens regarding vaccination. The objectives of the study were to investigate the vaccination coverage with a COVID-19 vaccine among students from different degree programs at the Medical universities in Bulgaria behaviors and attitudes toward vaccination with a COVID-19 vaccine. A prospective cross-sectional study in the period September 2021- March 2022 was conducted. Information on demographics, university program, year of study, general attitudes and behavior towards vaccines and attitudes and personal experience with COVID-19 and COVID-19 vaccines were collected. The chi-square test was used to test for associations and binominal logistic regression was used to identify possible predictors for vaccination. A total of 3050 students with a median age of 22 years, predominantly female took part in the study. Three-thirds of the students (73.5%) have been vaccinated against COVID-19. The main reasons for vaccine hesitancy in both group of students were the fear of side effects and the doubts about the safety of the vaccines although non-vaccinated students significantly more frequently express those fears. Respondents who considered to have: a) limited access to sufficient information to inform COVID-19 vaccine uptake; b) lack of public awareness and education campaigns about effectiveness and safety of COVID-19 vaccines; c) insufficient information about COVID-19 vaccines during the University education; and d) had a positive COVID-19 diagnosis were less likely to be vaccinated. Students who have not completed the mandatory immunization cycle according to country schedule were also less likely to have completed COVID-19 vaccination. The students showed an overall positive attitude towards the COVID-19 vaccines. Promoting informational campaigns that emphasize the vaccine's safety will be more effective to further increase the vaccination coverage with COVID-19 vaccines.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

The spatial and temporal variability in dietary preferences of juvenile three-spined stickleback Gasterosteus aculeatus, was studied across typical coastal habitats of Keret Archipelago, Kandalaksha Bay, the White Sea. Sampling of fish using beach seine was implemented in late July-early August and in late August, and zooplankton samples were collected to make a quantitative evaluation of abundance of potential prey items. Similarity Percentage (SIMPER) analysis implemented over the data obtained from stomach content analysis revealed five planktonic taxa mostly contributing to the diet of juvenile sticklebacks, of which copepod Temora longicornis was the most important prey item at marine sites, while Acartia longiremis prevailed in diet of fishes in marine lagoon. Calculation of selectivity index demonstrated that some taxa (e.g., A. longiremis) were always avoided by juvenile fishes, others (e.g. Microsetella norvegica) were firstly avoided and then selected in late August. Calculation of selectivity index was implemented per sample and per individual fish indicated that taxa like T. longicornis and were selected during the whole period of study, fishes demonstrated pronounced individual variation in prey selectivity. In general, data on selectivity indicated that despite juvenile sticklebacks feed on mostly available prey items, they can demonstrate taxonomic and size-specific prey selectivity.

Studies of dietary preferences of migratory species are of great importance as these species connect food webs of habitats across the migration route and thus represent trophic relationships between the spatially disjointed communities. Here we describe dietary preferences of threespine stickleback G. aculeatus in the White Sea during the spawning season using stable isotope and stomach content analyses. Both analyses indicated that during the spawning season, when sticklebacks spend most of the time in the inshore, their diet significantly consist of benthic species in contrast to the start of the spawning season when fishes migrating from the offshore are feeding on zooplankton. Also, we show that stickleback eggs contribute greatly to the diet of both male and female fishes. Using Bayesian mixing modelling we show that dietary preferences in females were broader than in males, and more variable during the spawning season. Males fed on eggs almost while guarding their nests. Both stomach contents and isotope signatures demonstrate that by the end of the spawning season sticklebacks again increase consumption of plankton, and isotope analysis proved to be more reliable tool to trace this change than stomach content analysis. Our results show that stable isotope and stomach content analyses well supplement each other in understanding of seasonal changes in dietary composition of stickleback.

The thermal properties of novel nanomaterials play a significant role in determining the performance of the material in technological applications. Herein, direct measurement of the temperature diffusivity of cellulose nanocomposite films was carried out by the micro-contact method. Polymer films containing up to 2%wt. of nanocellulose were synthesised by a simple chemical process. Films of a high optical transmittance T ≈ 80 % (for a 200- μ m-thick film), which were up to 44% crystalline, were characterised. Two different modalities of temperature diffusivity based on: 1) a resistance change and 2) micro-thermocouple detected modulation of a heat wave, were used for the polymer films with cross-sections of ∼ 100 μ m thickness. Twice different in-plane α ‖ and out-of-plane α ⊥ temperature diffusivities were directly determined with high fidelity: α ‖ = 2 . 12 × 10 − 7 m 2 /s and α ⊥ = 1 . 13 × 10 − 7 m 2 /s. An amorphous polyethylene terephthalate (PET) fiber was measured for comparison α ‖ = 1 . 15 × 10 − 7 m 2 /s. This work provides an example of a direct contact measurement of thermal properties of nanocellulose composite films. The thermal diffusivity, which is usually high in strongly interconnected networks and crystals, was investigated for the first time in this composite.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells, due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells – hMSCs) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSCs from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in normal cells, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 hours after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA repair system after X ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of normal cells from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

The focus of this article is the evaluation of the quality and the degree of community engagement in an expert-based, public-health communicative intervention for Alcohol Use Disorder (AUD). In 2023 the Canadian Alcohol Use Disorder Society collaborated with a grass-roots community health group, a regional health authority, and an academic participatory researcher to organize a working group to mount a social-marketing campaign to increase community support for AUD medical treatment in family-practice settings in a rural community in British Columbia. The partnership working group conducted a series of activities in the school system, the town council, and the community. This article covers the formative evaluation and the summative evaluation of the working group's effectiveness. The formative evaluation ("lessons learned" and "recommendations") consists of consensus evaluations of the quality of each activity using a variety of data sources. The formative evaluation followed improvement science methods and used consensus meetings to provide and reflect on formal and informal feedback. Formative results reflect the consensus of the participants in the working group and they record the reactions in the community. The summative evaluation measures evidence of community engagement found in transcribed text from meeting minutes. The summative evaluation used theory-based frameworks and text data visualization to assess the engagement dynamics of the working group. The summative evaluation helps to put the formative evaluation into perspective as communicative action. The summative evaluation validates the formative evaluation by revealing the communicative dynamics of engagement which resulted in the community’s increased capacity to understand and support Alcohol Use Disorder Treatment options. The working group and the entire intervention was seen by the participants and the public as a success and capable of replication. In a small community, it instilled new understandings and attitudes, bringing an emerging awareness of medication as an optional health mitigation strategy for Alcohol Use Disorder. Our study furthers this overall assessment by using theoretical constructs and analysis of communicative records to trace engagement characteristics of interest to researchers, societies, and community groups contemplating similar interventions in the future. The study also validates the effectiveness of communicative analysis as a measure of social-marketing for expert-based public health interventions.

Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here we study in silico and in vitro the structure of the protein, its interaction with RAE1, and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the membranes of the endoplasmic reticulum, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA-DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenesis of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

The accumulation of microplastics in the world oceans is one of the main global problems of the modern world. The Black Sea is the main source of seafood for people from several countries, including Bulgaria. The pollution of the Black sea is a result of various factors, especially anthropogenic. The present study demonstrated detailed MPs contamination of five fish species important for the commercial fishing (Garfish, Мullet, Knout goby, Pontic shad and Mediterranean horse mackerel) collected from the Sozopol area on the Bulgarian Black Sea coast. Within each microplastic morphological group, three size classes were recognized: 100-200 µm, 25-100 µm, and ≤ 25 µm. Microplastics were found in the soft tissues of all studied specimens but in a different ratio of pellets, fibers and fragments. Generally, the pellets were the most often registered particles, followed by irregularly-shaped fragments, whereas fibers were less numerous. The dominant part of the isolated plastics are made of polyethylene (PE), and polyethylene terephthalate (PET). Our results pointed out serious pollution with plastic particles in the Bulgarian Black Sea aquatory, which in the future may seriously affect the health of the fish population and also human health.

We demonstrate the use of a nanotechnology-based approach for the investigation of enzymatic activity of a single molecule of horseradish peroxidase with a solid-state nanopore. The artificial 5 nm solid-state nanopore has been formed in a 40-nm-thick silicon nitride structure. Single molecule of HRP has been entrapped into the nanopore. The activity of horseradish peroxidase (HRP) enzyme molecule inserted in the nanopore has been monitored by recording the time dependence of the ion current through the nanopore in the course of the reaction of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) oxidation reaction. We have found that in the process of ABTS oxidation in the presence of 2.5 mM hydrogen peroxide, individual HRP enzyme molecules are able to retain activity for approximately 700 seconds before a decrease in the ion current through the nanopore, which can be explained by structural changes of the enzyme.

The fabrication and characterisation of photo-anodes based on black-Si (b-Si) are presented using a photo-electrochemical cell in NaOH solution. Black-Si was fabricated by maskless dry plasma etching and was conformally coated by tens-of-nm of TiO2 using atomic layer deposition (ALD) with a top layer of CoO_x cocatalyst deposited by pulsed laser deposition (PLD). Low reflectivity R < % of Black-Si over the entire visible and near-IR (λ < 2 µm) spectral range is favourable in better absorption of light while an increased surface area facilities larger current densities. Photoelectrochemical performance of the heterostructured photoanode is discussed in terms of n-n junction between b-Si and TiO₂.

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within BLA governs these modulatory effects. However, most of the current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a neutral hippocampal-dependent task. We combined a weak version of the object location task (OLT) with mild predator odor exposure (POE) for our experiments. To investigate the role of the BLA in memory modulation, a subset of the animals (Wistar rats) were treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected either 90 minutes after drug infusion or 24 hours after the OLT test. The samples were used to determine the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc) - two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE is a behavioral paradigm suitable for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

(1) Background: Tooth extraction is one of the oldest and most well-known surgical procedures in dental medicine. It is still routinely performed to date by both general practitioners, oral surgeons, and dental undergraduates. The Benex extraction system allows for the extraction of teeth in vertical direction, which avoids most trauma against the surrounding alveolar bone and soft tissues; (2) Methods: The study included 56 patients who were recruited from the department of Oral Surgery at the Faculty of Dental Medicine, Medical University – Plovdiv. Patients were divided into two groups of 28 patients – Group I (control group) and Group II (study group). For each group the success of the extraction, buccal cortical plate preservation, pain experience and early wound healing were assessed; (3) Results: There was no statistical significance between the success of the extractions in both groups. The Benex extractions preserved the buccal cortical plate in 95% of the cases, whereas the forceps extractions only in 71.8%, which shows a statistical significance. On the seventh day patients in group II reported less pain, without a significant difference. There was a significantly bigger number of completely healed extraction wounds on the 10th day; (4) Conclusions: Atraumatic extractions allow for more hard and soft tissues to be preserved in the extraction site. This is all crucial for the successful outcome and aesthetically pleasing results of a following prosthetic or implant restoration.

During the last few decades bat lyssaviruses have become the topic of intensive molecular and epidemiological investigations. Since ancient times rhabdoviruses have caused fatal encephalitis in humans which has led to research into effective strategies for their eradication. Modelling of potential future cross-species virus transmissions forms a substantial component of the recent infection biology of rabies. In this article we summarise the available data on the phylogeography of both bats and lyssaviruses in Europe and the adjacent regions, especially in the contact zone between the Palearctic and Ethiopian realms. Within these zones three bat families are present with high potential for cross-species transmission and the spread of lyssaviruses in Phylogroup II to Europe (part of the western Palearctic). The lack of effective therapies for rabies viruses in Phylogroups II and III generates impetus for additional phylogenetic and virological research within this geographical region.

Heart failure (HF) has become a public health problem, but exact pathophysiology is still unknown. Western diet characterised with high sugar, high fat, red meat and processed meat, eggs, fried foods and sweetened beverages, may cause oxidative stress and inflammation, leading to oxidative dysfunction and adverse effects on cardiac-ultra-structure. However, only little is known about oxidative function of the of the myocardium and how oxidative dysfunction predispose Ca-overloading resulting in to physio-pathological remodelling leading to HF. Antioxidants such as flavonoids and polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential and nonessential amino acids that are rich in Indo-Mediterranean type of diets, may have protective roles in maintaining oxidative functions of the heart. The cardiac cells use fatty acids and glucose for the metabolic functions depending upon physiological and metabolic requirements. Apart from glucotoxicity, lipotoxicity is also damaging to cardiac cells which worsen in presence of deficiency of endogenous antioxidants and lower exogenous antioxidants in the diet. There is increased production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) due to high sugar and high fat diets, leading to oxidative dysfunction and Ca-overloading. The biological changes may begin with physiological remodelling to pathological remodelling due to oxidative damages. High fat diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve ejection fraction in a mouse model of HF. It is possible that increased supplementation of High Exogenous Antioxidant Restorative Treatment (HEART) diet; polyphenolics and flavonoids, vitamins, minerals, arginine, with omega-3 fatty acids, and cessation of red meat and egg may further improve the oxidative function of cardiac cells, resulting in the prevention and improvement in the earliest of the Six Stages of HF. Cohort studies and randomised, controlled trials would be necessary for demonstration of the role of HEART diet in the management of HF.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on demand drug release. In this study, a hybrid nanosystem for tempera-ture and pH sensitive delivery was prepared from MCM-41 nanoparticles grafted with newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemi-cally modified by carboxyl groups attachment. Later, they were grafted with agar (AA) and vi-nylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hy-drophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in different pH media and at different temperatures. At tumor simulating conditions (40ºC and pH 4.0) doxoru-bicin was almost completely released within 72 hours. The biocompatibility of the proposed na-noparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanopar-ticles for temperature-sensitive and pH-triggered drug delivery at the tumor site.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

Background: Pneumocystis pneumonia (PCP) commonly affects immunocompromised individuals, whereas in immunocompetent persons, it occurs relatively rarely, and in most cases the Pneumocystis infection is detected as an asymptomatic colonization. The present study aimed to establish the prevalence of Pneumocystis jirovecii infection in human hosts with different immune status (immunocompromised and immunocompetent), using molecular diagnostic methods, and to compare their diagnostic value with that of classical staining methods. Methods: We used the collected to this moment data from a prospective study on the prevalence of pneumocystosis among the Bulgarian population. Clinical specimens (including throat secretion, induced sputum, tracheal aspirate, and bronchoalveolar lavage collected from 220 patients suspected of PCP (153 immunocompetent and 67 immunocompromised patients) were examined with staining microscopic methods and real-time PCR for detection of P. jirovecii. Results: DNA of the pathogen was detected in 38 (17%) specimens (32 immunocompromised patients and 6 immunocompetent subjects). From all 220 clinical samples examined by staining methods, only in five (2%) P. jirovecii cysts were detected by the Gomori's stain. All patients with PCP were treated with trimethoprim-sulfamethoxazole, but in ten of them (HIV- positive patients) the disease was with fatal outcome. Conclusions: This study is the first for the country including the main available laboratory methods for diagnosis of human pneumocystosis in Bulgaria. Regarding the etiological diagnosis of PCP, in our study the sensitivity of real-time PCR was higher compared to the staining methods. The choice of a method for sample collection and examination has an important role in the efficiency of the laboratory diagnostics.

Mesenchymal stem cells (MSCs), whose main function is tissue repair, use collagen to restore the structural integrity of damaged tissue, maintaining its organization through concomitant remodelling. The non-enzymatic glycation of collagen is likely to compromise its communication with MSC, which indeed underlies various pathological conditions such as late complications of diabetes and aging. However, data on the effect of more early stages of collagen glycation on the MSC interaction are lacking. This study focused on the fate of in vitro glycated rat tail collagen (RTC) in contact with MSCs after its pre-exposure to glucose for 1 or 5 days. Using human adipose tissue-derived MSCs (ADMSCs), we showed that their interaction with glycated collagen is significantly altered, manifested morphologically by reduced cell spreading, less formation of focal adhesions, and weaker development of the actin cytoskeleton, further confirmed by ImageJ morphometric analysis. This suggests a poorer recognition of early glycated collagen by integrin receptors, possibly due to steric hindrance of their binding sites. These morphological events were also accompanied by greatly reduced fibril-like reorganization of adsorbed FITC-collagen (a sign of impaired remodeling), complemented by reduced sensitivity to proteases. The latter was confirmed in two ways: measuring directly FITC-collagen degradation by the attached cells and quantifying the proteolysis reduction upon exogenous addition of collagenase in a cell-free system. The mechanism of the observed effects is unclear, although differential scanning calorimetry confirmed the presence of weak structural changes in glycated collagen. All this led us to conclude that the reason for the morphological changes of ADMSCs is the impaired interaction with early-glycated collagen due to the hindrance of complementary sequences for integrins, which certainly also affects the mechanical remodeling of collagen. However, the impaired collagenolytic activity, together with the observed small changes in the thermal transition profile, undoubtedly indicate some internal changes in the structural organization of the collagen molecule occurring even at this early stage of glycation, which in turn contributes further to the impaired MSC remodeling activity.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Varying ratios of P407 and HPMC were applied in the presence and absence of SN-CX in order to optimize the gelation temperature (Tg) to values close to the physiological nasal such (30–34°C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature, whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way, while leading to an even further decrease in Tg. SN-CX-loaded nasal formulation composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

In this perspective, we give an overview of several less explored structural and optical characterisation techniques useful for biomaterials. New insights into the structure of natural fibres such as spider silk can be gained with minimal sample preparation. Electromagnetic radiation (EMR) over a broad range of wavelengths (from X-ray to THz) provides information of the structure of the material at cor- respondingly different length scales (nm-to-mm). When the sample features, such as the alignment of certain fibres, cannot be characterised optically, polarisation analysis of the optical images can provide further information on feature alignment. The 3D complexity of biological samples necessitates that there be feature measure- ments and characterisation over a large range of length scales. We discuss the issue of characterising complex shapes by analysis of the link between the color and struc- ture of spider scales and silk. For example, it is shown that the green-blue color of a spider scale is dominated by the chitin slab’s Fabry-P ́erot type reflectivity rather than the surface nanostructure. The use of a chromaticity plot simplifies complex spectra and enables quantification of the apparent colors. All the experimental data presented herein are used to support the discussion on the structure-color link in the characterisation of materials.

Tick-borne encephalitis virus (TBEV) is a RNA-containing enveloped virus, a member of the Flaviviridae family. Here we describe a detailed analysis of the size and structure of inactivated TBEV (the Sofyin-Chumakov TBEV strain, used in vaccines). Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, AFM, and NTA. All methods confirmed that the particles were monodisperse, and their mean size was ~50 nm. Cryo-EM data were used to obtain a 3D electron density model of the virus with clearly distinguishable E-proteins. STEM-EELS analysis detected phosphorous in the particles, which was interpreted as the RNA signal. Altogether, the described analytical procedures can be valuable for the further analysis of vaccine inactivated virus samples.

Parasomnias are a group of sleep disorders characterized by abnormal and unpleasant motor, verbal or behavioral events that occur during sleep or during transitions between wake and sleep states. They disrupt sleep and can have a detrimental impact on the individual experiencing them. Our goal was to identify types of parasomnias and their prevalence in the post-secondary student population and to explore students' coping strategies for parasomnias they found distressing. Seventy-seven post-secondary students completed the 21-item Munich Parasomnia Screening (MUPS) frequency scale. They also rated, on a 10-point scale, how disturbing each parasomnia was. Not only did 92% percent of students report at least one parasomnia, but our results also indicate that the vast majority of students experienced more than one parasomnia. This led us to investigate the likelihood of the co-occurrence of different parasomnias. With respect to the level of subjectively experienced distress, the most prevalent parasomnias were not always the more disturbing ones. Coded open-ended responses about what students do about the disturbing parasomnias indicate that grounding strategies and physical manipulation of one’s body were the most common, although most participants indicated that in spite of distress, they do nothing to cope. In conclusion, our study found a strikingly high prevalence of parasomnias in this sample of young adults and a lack of knowledge about effective means of dealing with these.

Background: According to newly published studies, patients with Coronavirus Disease 2019 (COVID-19) have significantly lower serum 25-hydroxyvitamin D 25(OH)D levels than those without the SARS-CoV-2 infection. Vitamin D insufficiency may be a predictor of poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit (ICU) admission and death, particularly in individuals with moderate-to-severe forms of COVID-19 requiring hospitalization. Materials and methods: This placebo-controlled five-day study was performed on 100 hospitalized COVID-19 patients with vitamin D insufficiency randomized into two groups. Vitamin D in the form of a sublingual sprayable microemulsion (LYL love your life® sunD3 LYLmicro™) was given three times daily after breakfast, lunch, and dinner (daily dose 12,000 IU) to 52 patients with blood vitamin D levels below 30 ng/ml. 48 patients in the control group received a placebo spray in the same daily regiment. Results: We observed a statistically significant increase by 8.6 ng/ml in median vitamin D level after five days of high-dose vitamin D3 spray therapy. 90.2% of subjects reached normal serum levels of vitamin D. There was a strong correlation between changes in vitamin D and C-reactive protein (CRP) levels in individuals with moderately severe disease (p<0.05), while mild and severe cases showed no statistical significance comparing case and control groups. There were no statistically significant changes in ferritin and interleukin-6 (IL-6) levels. Conclusions: In this study, we demonstrated the possibility to rapidly increase circulating levels of vitamin D just in 5 days of high-dose intervention and found a statistically significant decrease of CRP levels in patients with moderately severe COVID-19. We were not able to detect statistically significant changes in ferritin and IL-6 levels during the 5-day vitamin D intervention.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.