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The paper is the result of observing some important issues of continuous improvement in the world that changes rapidly and systemically. Knowledge is woven into intellectual property considered strategic good for the sustainability of companies. Therefore, specialists in corporate strategies strengthen the performance of the management system. Since the basic research motivation lies in viewing the synergistic action of people and intellectual capital in a digital environment, which competencies, the project manager needs to develop further? The aim of descriptive analysis is reflected in considering the content of knowledge and skills that are considered crucial in performing tasks in the field of project management, especially in relation to valid standards, regulations or legislation, but also changes incurred in the digital age. Desk analysis was conducted on a database on lifelong learning needs, as well as strategic estimates of necessary knowledge and skills for project management. The results show that the continuous intellectual development of the individual is the sine qua non creation and increasing the value of intellectual capital. An effective project manager is a source of positive social impact, with the potential to help raise people from poverty and efficient functioning of the system as a whole. Related literature in this paper, provided plausible facts on the need for permanent learning of the project manager in order to improve human resources and improve the competitive position of the market organization.

У раду је представљено пет приповједака Предрага Степановића. Настале у распону од средине шездесетих година прошлог до средине прве деценије овог вијека, оне, заједно са романом Преполовљени, чине цјелину по томе што су љубавног карактера, за разлику од бројних других Степановићевих приповједака и романа Живети у Мохачу, гдје преовладавају национално-историјске и породичне теме. Поред анализе ликова и саме љубавне тематике, рад се бави и формалним питањима, као што су појединачни наративни поступци, структура и композиција одабраних прича. Циљ рада је да истакне умјетничку вриједност Степановићевих дјела и да пробуди пажњу и интерес овдашње књижевно-научне и читалачке средине за овог врсног (а и првог!) савременог српског приповједача из Мађарске.

У раду се интерпретира роман Преполовљени савременог српског писца из Мађарске Предрага Степановића. Приказани су ликови, радња, структура и композиција, да би истовремено биле освијетљене интертекстуалне везе Преполовљених са остварењима домаће и свјетске књижевности, са Данојлићем и Дисом у мањој мјери, и са Тургењевљевим дјелима Дим, Рудин и Фауст, као и са Гетеовим Фаустом, у већој. Рад такође пружа увид у заједничку тему овог Степановићевог романа и споменутих дјела других аутора, а то је тема несрећне љубави. Циљ је да се допуне и продубе постојеће анализе Степановићевог дјела; да се о Преполовљенима каже нешто о чему до сада није писано. Тај циљ је тим пречи што је у питању не само први роман нашег значајног савременог писца, његова првобјављена самостална књига, него је појава Преполовљених важан, незаобилазан датум у историји српске књижевности и зато што је то први савремени српски роман у Мађарској.

The subject of this research is to analyze the way in which students use content on the Internet. The emphasis is on the educational and informational needs of students in the selected statistical sample. Internet sites are structured according to the preferences of students. In this sense, have been explicitly included in the analysis of educational content, information, and entertainment. After a field study on a sample of 238 students conducted a quantitative analysis and qualitative assessment derived. Data were processed in SPSS software. The results showed how students estimate the total amount of time you spend on the Internet. Conclusions also apply to the assessment of the same time, as a possible limiting factors in terms of contacts, which have to do with real social environment. Data evaluation is based on the need to analyze the habits and behavior of students on the Internet as well as their organization of time in relation to the Work-life balance.

The issue of lifelong learning is linked to the voluntary and motivated to seek knowledge from personal or organizational reasons. The fact that an individual learns driven by personal career goals, desire for self improvement and motivation refers to the importance of lifelong learning for the entire social inclusion, sustainability, and competitiveness and employment. The common denominator of all the problems of investment in education is an issue of increasing allocations to the social issues, the pace that in this area manifest needs. Relative resource constraints requires that the investment in professional development taking place in accordance with the expected contribution to the creation of new value, increase productivity and social development of society as a whole. Respecting this request, in general, should provide maximum socio-economic effects with minimal investment. Precise measurement is achieved by tools of economic analysis: cost & benefit, economic sensitivity analysis, risk assessment.

La mayoría de los ciudadanos europeos no cumplen con un adecuado aporte de calcio y vitamina D en sus dietas, por lo que los suplementos de ambos pueden ayudar a cubrir las necesidades. El déficit de vitamina D puede conducir a una menor absorción de calcio, un aumento del remodelado óseo y un incremento de la pérdida de masa ósea; además, el déficit de vitamina D reduce la función muscular y aumenta el riesgo de caidas. El carbonato de calcio es la forma farmacéutica de uso más común, debido a su perfil coste/eficacia, de administrar suplementos de calcio en nuestro medio. Otras sales como el lactato y gluconato presentan una menor concentración del elemento y son poco prácticas. El objeto del presente artículo es poner de manifiesto la relevancia de la asociación calcio-vitamina D, su protagonismo en la prevención y tratamiento de la osteoporosis, así como las formas farmacéuticas más frecuentes y útiles para su uso clínico.

Cystic Fibrosis (CF) airway disease is characterized by impaired mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation. Pulmonary disease is the leading cause of morbidity and mortality in people with CF and is due to progressive airflow obstruction and ultimately respiratory failure. One of the earliest abnormalities in CF airway disease is the recruitment of neutrophils to the lungs. Neutrophil activation leads to the release of their intracellular content, including neutrophil elastase (NE), that damages lung tissues in CF. Our goal is to characterize a known bacterial NE inhibitor, ecotin, in the CF airway environment. Our results indicate that ecotins cloned from four Gram-negative bacterial species ( Campylobacter rectus , Campylobacter showae , Escherichia coli and Pseudomonas aeruginosa) inhibit NE activity in CF sputum samples in a dose-dependent manner. Although we observed differences in the NE-inhibitory activity of the tested ecotins with the Campylobacter homologs being the most effective in NE inhibition in CF sputa, none of the ecotins impaired the ability of human neutrophils to kill major CF respiratory pathogens, P. aeruginosa or S. aureus , in vitro . Overall, we demonstrate that bacterial ecotins inhibit NE activity in CF sputa without compromising bacterial killing by neutrophils., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Loss of the flagellum marks the pathoadaptation of Pseudomonas aeruginosa to the cystic fibrosis (CF) airway environment during lung disease. Losing the flagellum is advantageous to the bacterium as the flagellum can be recognized by immune cells. The primary purpose of the flagellum is, however, to provide motility to the bacterium. Our goal was to determine whether the loss of flagellar motility or the loss of flagellum expression contributes to P. aeruginosa lung infection in CF. To address this, wild-type and gut-corrected FABP-human cystic fibrosis transmembrane conductance regulator (hCFTR) mice deficient in the murine Cftr gene were infected intratracheally with lethal doses of wild-type or flagellum-deficient P. aeruginosa . While there was no significant difference in the survival of wild-type mice after infection with either of the bacterial strains, a significantly higher mortality was observed in FABP-hCFTR mice infected with flagellum-deficient P. aeruginosa , compared to mice infected with their flagellated counterparts. When FABP-hCFTR mice were infected with isogenic, motility-deficient flagellated mutants, animal survival and lung bacterial titers were similar to those observed in mice infected with the wild-type bacterium. Airway levels of neutrophils and the amount neutrophil elastase were similar in mice infected with either the wild-type bacteria or the flagellum-deficient P. aeruginosa . Our results show that FABP-hCFTR mice have a different response to flagellum loss in P. aeruginosa compared to wild-type animals. The loss of flagellum expression, rather than the loss of motility, is the main driver behind the increased virulence of flagellum-deficient P. aeruginosa in CF. These observations provide new insight into P. aeruginosa virulence in CF.IMPORTANCE Pseudomonas aeruginosa , a major respiratory pathogen in cystic fibrosis, is known to lose its flagellum during the course of infection in the airways. Here, we show that the loss of flagellum leads to a more enhanced virulence in Cftr-deficient cystic fibrosis mice than in control animals. Loss of flagellum expression, rather than the loss of flagellar swimming motility, represents the main driver behind this increased virulence suggesting that this appendage plays a specific role in P. aeruginosa virulence in cystic fibrosis airways., Competing Interests: The authors declare no conflict of interest.

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN - ), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN - reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN - . In this review, we discuss roles of HOSCN/SCN - in immunity and potential therapeutic implications for combating infections., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. In the present study, we show hepcidin expression in both mouse (mBMSC) and human BMSCs (hBMSC). We observed a hBMSC hepcidin-dependent degradation of ferroportin in HEK-293 reporter cells in vitro. In human and mouse bone marrows (BM) we detected hepcidin-positive BMSCs in close proximity to hematopoietic progenitors. The conditioned culture medium of hBMSCs significantly reduced bacterial proliferation that was partially blocked by a hepcidin-neutralizing antibody. Similarly, medium in which hepcidin-deficient (Hamp -/- ) mouse BMSCs had been grown was significantly less effective in reducing bacterial counts than the medium of wild-type cells. In a zymosan-induced peritonitis mouse model we found that mBMSC-derived hepcidin reduced the number of invading polymorphonuclear (PMN) cells in the peritoneal cavity. Our results show that BMSC-derived hepcidin has antimicrobial properties in vitro and also reduces inflammation in vivo. We conclude that hepcidin should be added to the expanding arsenal of agents available to BMSCs to fight infections and inflammation., (© 2024. The Author(s).)

Introduction: Severe forms of COVID-19, the disease caused by SARS-CoV-2, are characterized by acute respiratory distress syndrome, robust lung inflammation and death in some patients. Strong evidence has been accumulating that polymorphonuclear neutrophilic granulocytes (PMN) play an important role in the pathophysiology of severe COVID-19. SARS-CoV-2 directly induces in vitro PMN activation, mainly the release of neutrophil extracellular traps (NETs). However, the viral components inducing this PMN response remain unclear., Methods: In this work human PMN responses were assessed in vitro in response to the spike (S) protein of two different SARS-CoV-2 variants, anti-S IgG1 antibodies or immune complexes formed by them. Production of reactive oxygen species (ROS) was measured by Diogenes-based chemiluminescence. Release of myeloperoxidase (MPO) was assessed by ELISA while secretion of a list of cytokines and growth factors was determined by high-performance multiplex cytokine assay., Results and Discussion: We show that the SARS-CoV-2 Omicron variant S protein and anti-spike IgG1, either alone or together, stimulate ROS production in human PMNs. We also observed that the SARS-CoV-2 Wuhan S protein and anti-S IgG1 antibody together trigger MPO release from PMNs. Based on the relevance of SARS-CoV-2 and influenza co-infections, we have also investigated the impact of influenza virus infection on the previous PMN responses to S proteins or anti-S antibodies. We did not detect any significant effect of influenza co-infection on ROS generation in PMNs. Our data also show that PMN stimulation by S proteins induced the release of different chemokines, growth factors, regulatory and proinflammatory cytokines. Overall, our findings show that the SARS-CoV-2 S protein, an anti-spike IgG1 antibody or their immune complex, promote oxidative responses of PMNs in a variant-dependent manner, contributing to a better understanding of the role of PMN responses during SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Almeida, Fantone, Sarr, Ashtiwi, Channell, Grenfell, Martins-Filho and Rada.)

Introduction: While cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth., Methods: In this work we undertook an unbiased approach to explore the systemic autoantibody repertoire in CF using autoantibody microarrays., Results and Discussion: Our results show higher levels of several new autoantibodies in the blood of people with CF (PwCF) compared to control subjects. Some of these are IgA autoantibodies targeting neutrophil components or autoantigens linked to neutrophil-mediated tissue damage in CF. We also found that people with CF with higher systemic IgM autoantibody levels have lower prevalence of S. aureus infection. On the other hand, IgM autoantibody levels in S. aureus -infected PwCF correlate with lung disease severity. Diabetic PwCF have significantly higher levels of IgA autoantibodies in their circulation compared to nondiabetic PwCF and several of their IgM autoantibodies associate with worse lung disease. In contrast, in nondiabetic PwCF blood levels of IgA autoantibodies correlate with lung disease. We have also identified other autoantibodies in CF that associate with P. aeruginosa airway infection. In summary, we have identified several new autoantibodies and associations of autoantibody signatures with specific clinical features in CF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yadav, Li, Huang, Bridges, Kahlenberg, Stecenko and Rada.)