Search results for: Marianna Russo
Commenced in January 2007
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Edition: International
Paper Count: 42

Search results for: Marianna Russo

12 Disparities in Suicide and Mental Health among Student Athletes of Ethnic and Racial Minorities Compared to Their White Non-latinx Counterparts

Authors: Elizabeth Russo, Angelica Terepka

Abstract:

The present paper reviews literature examining trends among suicide, suicidal ideation, and mental illness rates in ethnic and racial minority student-athletes. While the rates of suicide amongst student athlete populations is lower than rates of suicide seen in the general student populations, there is a discrepancy amongst rates of suicide in student athletes; specifically, those identifying with racial and ethnic minority backgrounds endorse higher rates of suicidal ideation. The samples from the existing literature consisted of White, Black, Hispanic/Latinx, Asian/ Pacific Islander, Multiracial, and Native American student-athletes. Studies suggest that ethnic and racial minority students are more susceptible to suicide, depression, and other mental health concerns compared to their white counterparts. Across the literature, White student athletes appeared to have more social and academic support from fellow classmates, university administration and professors, and staff within their athletic departments. Student athletes who did not identify as White endorsed higher rates of loneliness, felt ethnically and racially underrepresented within their athletic department, and endorsed lack of appropriate medical treatment for injuries by athletic department medical staff. Additionally, non-White student athletes receive less peer support and must balance additional stressors such as discrimination in contrast to their White/non-Latinx peers. Recommendations for athletic departments and mental health providers supporting student athletes who identify as racial and ethnic minorities are discussed.

Keywords: racial and ethnic minority, suicide, student-athlete, suicidal ideation

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11 Multiscale Process Modeling Analysis for the Prediction of Composite Strength Allowables

Authors: Marianna Maiaru, Gregory M. Odegard

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During the processing of high-performance thermoset polymer matrix composites, chemical reactions occur during elevated pressure and temperature cycles, causing the constituent monomers to crosslink and form a molecular network that gradually can sustain stress. As the crosslinking process progresses, the material naturally experiences a gradual shrinkage due to the increase in covalent bonds in the network. Once the cured composite completes the cure cycle and is brought to room temperature, the thermal expansion mismatch of the fibers and matrix cause additional residual stresses to form. These compounded residual stresses can compromise the reliability of the composite material and affect the composite strength. Composite process modeling is greatly complicated by the multiscale nature of the composite architecture. At the molecular level, the degree of cure controls the local shrinkage and thermal-mechanical properties of the thermoset. At the microscopic level, the local fiber architecture and packing affect the magnitudes and locations of residual stress concentrations. At the macroscopic level, the layup sequence controls the nature of crack initiation and propagation due to residual stresses. The goal of this research is use molecular dynamics (MD) and finite element analysis (FEA) to predict the residual stresses in composite laminates and the corresponding effect on composite failure. MD is used to predict the polymer shrinkage and thermomechanical properties as a function of degree of cure. This information is used as input into FEA to predict the residual stresses on the microscopic level resulting from the complete cure process. Virtual testing is subsequently conducted to predict strength allowables. Experimental characterization is used to validate the modeling.

Keywords: molecular dynamics, finite element analysis, processing modeling, multiscale modeling

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10 Comprehensive Profiling and Characterization of Untargeted Extracellular Metabolites in Fermentation Processes: Insights and Advances in Analysis and Identification

Authors: Marianna Ciaccia, Gennaro Agrimi, Isabella Pisano, Maurizio Bettiga, Silvia Rapacioli, Giulia Mensa, Monica Marzagalli

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Objective: Untargeted metabolomic analysis of extracellular metabolites is a powerful approach that focuses on comprehensively profiling in the extracellular space. In this study, we applied extracellular metabolomic analysis to investigate the metabolism of two probiotic microorganisms with health benefits that extend far beyond the digestive tract and the immune system. Methods: Analytical techniques employed in extracellular metabolomic analysis encompass various technologies, including mass spectrometry (MS), which enables the identification of metabolites present in the fermentation media, as well as the comparison of metabolic profiles under different experimental conditions. Multivariate statistical analysis techniques like principal component analysis (PCA) or partial least squares-discriminant analysis (PLS-DA) play a crucial role in uncovering metabolic signatures and understanding the dynamics of metabolic networks. Results: Different types of supernatants from fermentation processes, such as dairy-free, not dairy-free media and media with no cells or pasteurized, were subjected to metabolite profiling, which contained a complex mixture of metabolites, including substrates, intermediates, and end-products. This profiling provided insights into the metabolic activity of the microorganisms. The integration of advanced software tools has facilitated the identification and characterization of metabolites in different fermentation conditions and microorganism strains. Conclusions: In conclusion, untargeted extracellular metabolomic analysis, combined with software tools, allowed the study of the metabolites consumed and produced during the fermentation processes of probiotic microorganisms. Ongoing advancements in data analysis methods will further enhance the application of extracellular metabolomic analysis in fermentation research, leading to improved bioproduction and the advancement of sustainable manufacturing processes.

Keywords: biotechnology, metabolomics, lactic bacteria, probiotics, postbiotics

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9 Catalytic Soot Gasification in Single and Mixed Atmospheres of CO2 and H2O in the Presence of CO and H2

Authors: Yeidy Sorani Montenegro Camacho, Samir Bensaid, Nunzio Russo, Debora Fino

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LiFeO2 nano-powders were prepared via solution combustion synthesis (SCS) method and were used as carbon gasification catalyst in a reduced atmosphere. The gasification of soot with CO2 and H2O in the presence of CO and H2 (syngas atmosphere) were also investigated under atmospheric conditions using a fixed-bed micro-reactor placed in an electric, PID-regulated oven. The catalytic bed was composed of 150 mg of inert silica, 45 mg of carbon (Printex-U) and 5 mg of catalyst. The bed was prepared by ball milling the mixture at 240 rpm for 15 min to get an intimate contact between the catalyst and soot. A Gas Hourly Space Velocity (GHSV) of 38.000 h-1 was used for the tests campaign. The furnace was heated up to the desired temperature, a flow of 120 mL/min was sent into the system and at the same time the concentrations of CO, CO2 and H2 were recorded at the reactor outlet using an EMERSON X-STREAM XEGP analyzer. Catalytic and non-catalytic soot gasification reactions were studied in a temperature range of 120°C – 850°C with a heating rate of 5 °C/min (non-isothermal case) and at 650°C for 40 minutes (isothermal case). Experimental results show that the gasification of soot with H2O and CO2 are inhibited by the H2 and CO, respectively. The soot conversion at 650°C decreases from 70.2% to 31.6% when the CO is present in the feed. Besides, the soot conversion was 73.1% and 48.6% for H2O-soot and H2O-H2-soot gasification reactions, respectively. Also, it was observed that the carbon gasification in mixed atmosphere, i.e., when simultaneous carbon gasification with CO2 and steam take place, with H2 and CO as co-reagents; the gasification reaction is strongly inhibited by CO and H2, as well has been observed in single atmospheres for the isothermal and non-isothermal reactions. Further, it has been observed that when CO2 and H2O react with carbon at the same time, there is a passive cooperation of steam and carbon dioxide in the gasification reaction, this means that the two gases operate on separate active sites without influencing each other. Finally, despite the extreme reduced operating conditions, it has been demonstrated that the 32.9% of the initial carbon was gasified using LiFeO2-catalyst, while in the non-catalytic case only 8% of the soot was gasified at 650°C.

Keywords: soot gasification, nanostructured catalyst, reducing environment, syngas

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8 Multiscale Process Modeling of Ceramic Matrix Composites

Authors: Marianna Maiaru, Gregory M. Odegard, Josh Kemppainen, Ivan Gallegos, Michael Olaya

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Ceramic matrix composites (CMCs) are typically used in applications that require long-term mechanical integrity at elevated temperatures. CMCs are usually fabricated using a polymer precursor that is initially polymerized in situ with fiber reinforcement, followed by a series of cycles of pyrolysis to transform the polymer matrix into a rigid glass or ceramic. The pyrolysis step typically generates volatile gasses, which creates porosity within the polymer matrix phase of the composite. Subsequent cycles of monomer infusion, polymerization, and pyrolysis are often used to reduce the porosity and thus increase the durability of the composite. Because of the significant expense of such iterative processing cycles, new generations of CMCs with improved durability and manufacturability are difficult and expensive to develop using standard Edisonian approaches. The goal of this research is to develop a computational process-modeling-based approach that can be used to design the next generation of CMC materials with optimized material and processing parameters for maximum strength and efficient manufacturing. The process modeling incorporates computational modeling tools, including molecular dynamics (MD), to simulate the material at multiple length scales. Results from MD simulation are used to inform the continuum-level models to link molecular-level characteristics (material structure, temperature) to bulk-level performance (strength, residual stresses). Processing parameters are optimized such that process-induced residual stresses are minimized and laminate strength is maximized. The multiscale process modeling method developed with this research can play a key role in the development of future CMCs for high-temperature and high-strength applications. By combining multiscale computational tools and process modeling, new manufacturing parameters can be established for optimal fabrication and performance of CMCs for a wide range of applications.

Keywords: digital engineering, finite elements, manufacturing, molecular dynamics

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7 Comparison of Soils of Hungarian Dry and Humid Oak Forests Based on Changes in Nutrient Content

Authors: István Fekete, Imre Berki, Áron Béni, Katalin Juhos, Marianna Makádi, Zsolt Kotroczó

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The average annual precipitation significantly influences the moisture content of the soils and, through this, the decomposition of the organic substances in the soils, the leaching of nutrients from the soils, and the pH of the soils. Climate change, together with the lengthening of the vegetation period and the increasing CO₂ level, can increase the amount of biomass that is formed. Degradation processes, which accelerate as the temperature increases and slow down due to the drying climate, and the change in the degree of leaching can cancel out or strengthen each other's effects. In the course of our research, we looked for oak forests with climate-zonal soils where the geological, geographical and ecological background conditions are as similar as possible, apart from the different annual precipitation averages and the differences that can arise from them. We examined 5 dry and 5 humid Hungarian oak soils. Climate change affects the soils of drier and wetter forests differently. The aim of our research was to compare the content of carbon, nitrogen and some other nutrients, as well as the pH of the soils of humid and dry forests. Showing the effects of the drier climate on the tested soil parameters. In the case of the examined forest soils, we found a significant difference between the soils of dry and humid forests: in the case of the annual average precipitation values (p≥ 0.0001, for dry forest soils: 564±5.2 mm; for humid forest soils: 716±3.8 mm) for pH (p= 0.0004, for dry forest soils: 5.49±0.16; for wet forest soils: 5.36±0.21); for C content (p= 0.0054, for dry forest soils: 6.92%±0.59; for humid forest soils 3.09%±0.24), for N content (p= 0.0022, dry forest in the case of soils: 0.44%±0.047; in the case of humid forest soils: 0.23%±0.013), for the K content (p=0.0017, in the case of dry forest soils: 5684±732 (mg/kg); in the case of humid forest soils 2169±196 (mg/kg)), for the Ca content (p= 0.0096, for dry forest soils: 8207±2118 (mg/kg); for wet forest soils 957±320 (mg/kg)). No significant difference was found in the case of Mg. In a wetter environment, especially if the moisture content of the soil is also optimal for the decomposing organisms during the growing season, the decomposition of organic residues accelerates, and the processes of leaching from the soil are also intensified. The different intensity of the leaching processes is also well reflected in the quantitative differences of Ca and K, and in connection with these, it is also reflected in the difference in pH values. The differences in the C and N content can be explained by differences in the intensity of the decomposition processes. In addition to warming, drying is expected in a significant part of Hungary due to climate change. Thus, the comparison of the soils of dry and humid forests allows us to predict the subsequent changes in the case of the examined parameters.

Keywords: soil nutrients, precipitation difference, climate change, organic matter decomposition, leaching

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6 Functionalized Spherical Aluminosilicates in Biomedically Grade Composites

Authors: Damian Stanislaw Nakonieczny, Grazyna Simha Martynkova, Marianna Hundakova, G. Kratosová, Karla Cech Barabaszova

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The main aim of the research was to functionalize the surface of spherical aluminum silicates in the form of so-called cenospheres. Cenospheres are light ceramic particles with a density between 0.45 and 0.85 kgm-3 hat can be obtained as a result of separation from fly ash from coal combustion. However, their occurrence is limited to about 1% by weight of dry ash mainly derived from anthracite. Hence they are very rare and desirable material. Cenospheres are characterized by complete chemical inertness. Mohs hardness in range of 6 and completely smooth surface. Main idea was to prepare the surface by chemical etching, among others hydrofluoric acid (HF) and hydrogen peroxide, caro acid, silanization using (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) to obtain the maximum development and functionalization of the surface to improve chemical and mechanical connection with biomedically used polymers, i.e., polyacrylic methacrylate (PMMA) and polyetheretherketone (PEEK). These polymers are used medically mainly as a material for fixed and removable dental prostheses and PEEK spinal implants. The problem with their use is the decrease in mechanical properties over time and bacterial infections fungal during implantation and use of dentures. Hence, the use of a ceramic filler that will significantly improve the mechanical properties, improve the fluidity of the polymer during shape formation, and in the future, will be able to support bacteriostatic substances such as silver and zinc ions seem promising. In order to evaluate our laboratory work, several instrumental studies were performed: chemical composition and morphology with scanning electron microscopy with Energy-Dispersive X-Ray Probe (SEM/EDX), determination of characteristic functional groups of Fourier Transform Infrared Spectroscopy (FTIR), phase composition of X-ray Diffraction (XRD) and thermal analysis of Thermo Gravimetric Analysis/differentia thermal analysis (TGA/DTA), as well as assessment of isotherm of adsorption with Brunauer-Emmett-Teller (BET) surface development. The surface was evaluated for the future application of additional bacteria and static fungus layers. Based on the experimental work, it was found that orated methods can be suitable for the functionalization of the surface of cenosphere ceramics, and in the future it can be suitable as a bacteriostatic filler for biomedical polymers, i.e., PEEK or PMMA.

Keywords: bioceramics, composites, functionalization, surface development

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5 MAFB Expression in LPS-Induced Exosomes: Revealing the Connection to sepsis-trigerred Hepatic Injury

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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4 Individual Differences in Affective Neuroscience Personality Traits Predict Several Dimensions of Psychological Wellbeing. A Cross-Sectional Study in Healthy Subjects

Authors: Valentina Colonnello, Paolo Maria Russo

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Decades of cross-species affective neuroscience research by Panksepp and others have identified basic evolutionarily preserved subcortical emotional systems that humans share with mammals and many vertebrates. These primary emotional systems encode unconditional affective responses and contribute to the development of personality traits throughout ontogenesis and interactions with the environment. The Affective Neuroscience Personality Scale (ANPS) measures individual differences in affective personality traits associated with the basic emotional systems of CARE, PLAY, SEEKING, SADNESS, FEAR, and ANGER, along with Spirituality, which is a more cognitively and socially refined expression of affectivity. Though the ANPS’s power to predict human psychological distress has been documented, to the best of our knowledge, its predictive power for psychological wellbeing has not been explored. This study therefore investigates the relationship between affective neuroscience traits and psychological wellbeing facets. Because the emotional systems are thought to influence cognitively-mediated mental processes about the self and the world, understanding the relationship between affective traits and psychological wellbeing is particularly relevant to understanding the affective dimensions of health. In a cross-sectional study, healthy participants (n = 402) completed the ANPS and the Psychological Wellbeing scale. Multiple regressions revealed that each facet of wellbeing was explained by two to four affective traits, and each trait was significantly related to at least one aspect of wellbeing. Specifically, SEEKING predicted all the wellbeing facets, except for positive relations; CARE predicted personal growth, positive relations, purpose in life, and self-acceptance; PLAY and, inversely, ANGER predicted positive relations; SADNESS inversely predicted autonomy, while FEAR inversely predicted purpose in life. SADNESS and FEAR inversely predicted environmental mastery and self-acceptance. Finally, Spirituality predicted personal growth, positive relations, and self-acceptance. These findings are the first to show the relationship between affective neuroscience personality traits and psychological wellbeing. They also call attention to the distinctive role of FEAR and PANIC traits in psychological wellbeing facets, thereby complementing or even overcoming the traditional personality approach to neuroticism as a global trait.

Keywords: affective neuroscience, individual differences, personality, wellbeing

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3 A Design Methodology and Tool to Support Ecodesign Implementation in Induction Hobs

Authors: Anna Costanza Russo, Daniele Landi, Michele Germani

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Nowadays, the European Ecodesign Directive has emerged as a new approach to integrate environmental concerns into the product design and related processes. Ecodesign aims to minimize environmental impacts throughout the product life cycle, without compromising performances and costs. In addition, the recent Ecodesign Directives require products which are increasingly eco-friendly and eco-efficient, preserving high-performances. It is very important for producers measuring performances, for electric cooking ranges, hobs, ovens, and grills for household use, and a low power consumption of appliances represents a powerful selling point, also in terms of ecodesign requirements. The Ecodesign Directive provides a clear framework about the sustainable design of products and it has been extended in 2009 to all energy-related products, or products with an impact on energy consumption during the use. The European Regulation establishes measures of ecodesign of ovens, hobs, and kitchen hoods, and domestic use and energy efficiency of a product has a significant environmental aspect in the use phase which is the most impactful in the life cycle. It is important that the product parameters and performances are not affected by ecodesign requirements from a user’s point of view, and the benefits of reducing energy consumption in the use phase should offset the possible environmental impact in the production stage. Accurate measurements of cooking appliance performance are essential to help the industry to produce more energy efficient appliances. The development of ecodriven products requires ecoinnovation and ecodesign tools to support the sustainability improvement. The ecodesign tools should be practical and focused on specific ecoobjectives in order to be largely diffused. The main scope of this paper is the development, implementation, and testing of an innovative tool, which could be an improvement for the sustainable design of induction hobs. In particular, a prototypical software tool is developed in order to simulate the energy performances of the induction hobs. The tool is focused on a multiphysics model which is able to simulate the energy performances and the efficiency of induction hobs starting from the design data. The multiphysics model is composed by an electromagnetic simulation and a thermal simulation. The electromagnetic simulation is able to calculate the eddy current induced in the pot, which leads to the Joule heating of material. The thermal simulation is able to measure the energy consumption during the operational phase. The Joule heating caused from the eddy currents is the output of electromagnetic simulation and the input of thermal ones. The aims of the paper are the development of integrated tools and methodologies of virtual prototyping in the context of the ecodesign. This tool could be a revolutionary instrument in the field of industrial engineering and it gives consideration to the environmental aspects of product design and focus on the ecodesign of energy-related products, in order to achieve a reduced environmental impact.

Keywords: ecodesign, energy efficiency, induction hobs, virtual prototyping

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2 In vivo Evaluation of LAB Probiotic Potential with the Zebrafish Animal Model

Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

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Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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1 Broad Host Range Bacteriophage Cocktail for Reduction of Staphylococcus aureus as Potential Therapy for Atopic Dermatitis

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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