The role of Ramsar sites in the creation of integral tourism offer of Vojvodina

Биодиверзитет, геонаслеђе, разноврсност екосистема, природних предела и културе локалних заједница у Рамсарским подручјима Војводине и њиховој околини, представљају добар потенцијал и основу за развој туризма у Војводини. Изузетна вредност, као и угроженост и нестајање оваквих простора довела је до опсежних истраживања и расправа о њиховој заштити и рационалном коришћењу. Важан сегмент мудрог коришћења влажних станишта припада туризму, који може значајно допринети заштити и очувању природних вредности на којима се заснива туристичка атрактивност Рамсарских подручја, кроз остваривање новчаних прихода и коришћењу истих за финансирање трошкова заштите. Основни циљ истраживања у оквиру ове дисертације је постављање научно релевантних методолошких основа организације и реализације туризма у Рамсарким подручјима Војводине, које ће бити апликативно прихватљиве и објашњене адекватним теоријским оквиром. Задаци истраживања односили су се на разраду проблематике туризма у Рамсарским подручјима Војводине, с једне стране анализом мотивских вредности којима располажу ови локалитети, а са друге анализом задовољства туриста који их посећују. Како се задовољство туриста тумачи као водећи индикатор ка успостављању дугорочне одрживости, јер је пресудан за поновљене посете дестинацији, као и позитивне/негативне препоруке будућим посетиоцима, у дисертацији је урађена анализа фактора који утичу на задовољство туриста у Рамсарским подручјима Војводине. Резултати истраживања показују да су туристи у Рамсарским подручјима најзадовољнији природним туристичким мотивима. Када се ради о задовољству услугом, половина испитаника је изразила неутралан став, док је већи проценат друге половине испитаника имало позитиван став, односно били су задовољни услугом у Рамсарским подручјима. Ово нам говори да квалитет услуге који се ii пружа туристима у Рамсарским подручјима Војводине није на завидном нивоу и да би свакако требало порадити на његовом унапређењу.Biodiversity, geoheritage, diversity of ecosystems, natural landscapes and local communities’ culture in Ramsar sites of Vojvodina and their surrounding, make a good potential and the grounds for the development of tourism in Vojvodina. Their exquisite value, as well as these sites being endangered and disappearing, led to extensive research and discussions concerning their protection and rational use. An important segment of the wise use of wetlands belongs to tourism, as tourism can significantly contribute to the protection and preservation of natural values the tourist attractiveness of the Ramsar sites is based on, by earning monetary income and using that income to finance the costs of protection. The basic goal of the research conducted through this dissertation was to set the scientifically-relevant methodological bases for the organization and realization of tourist activities in Ramsar sites of Vojvodina that will be applicable and explained by adequate theoretical framework. The research tasks referred to the elaboration of issues concerning tourism in Ramsar sites of Vojvodina. On the one hand the tasks concerned the analysis of motivational values these sites have, and on the other hand they concerned the analysis of the satisfaction of tourists visiting those sites. As tourist satisfaction is interpreted as the leading indicator towards the establishing of long-term sustainability, being decisive for the repeated visits to the destination, as well as for the positive/negative recommendations to future visitors, an analysis concerning the factors affecting tourist satisfaction in Ramsar sites of Vojvodina has been performed within this dissertation. The research results show that tourists visiting Ramsar sites are most satisfied with natural-based tourist motifs. When it comes to satisfaction with services, one half of the examinees stated their neutral position, whereas more examinees among the other half expressed positive position, i.e. they were satisfied with the services provided at Ramsar sites. This tells us that the quality of services provided to tourist in the Ramsar iv sites of Vojvodina is not at an enviable level and that it should certainly be improved

Transformation of spas in Serbia into modern centers of spa and wellness tourism

Имајући у виду високе стопе раста spa и wellness туризма на глобалном нивоу, квантитет и квалитет конкурентских понуда бележи континуирани раст, те је у таквим условима врло захтеван задатак изборити се за адекватну позицију на тржишту. Будући да се Србија, упркос изузетно повољним природним ресурсима за развој бањског туризма, још увек убраја у недовољно развијене дестинације, од посебног значаја за будуће унапређење овог вида туризма и позиционирање бања као туристичких дестинација на међународном туристичком тржишту, јесте управо њихова трансформација од традиционалних лечилишта у модерне центре spa и wellness туризма. Основни циљ истраживања у оквиру ове дисертације је постављање научно релевантних основа тумачења процеса трансформације традиционалних бања Србије у савремене центре spa и wellness туризма, које ће бити апликативно прихватљиве и поткрепљене адекватним теоријским оквиром. Задаци истраживања односили су се на разраду проблематике туризма у бањама Србије, с једне стране анализом мотивације туриста који посећују бање, а са друге анализом атрибута атрактивности бања. У дисертацији се покушао развити модел који би обухватио све факторе који утичу на процес доношења одлуке туриста када је реч о избору бање као места за одмор. Досадашње студије или су обухватале само мотивацију (push и pull мотиве) или само ограничења, док је у овој студији представљен интегралан модел који укључује сва три фактора. Разумевање и прилагођавање мотивацији и понашању туриста је једини начин да бање буду конкурентне на туристичком тржишту. Анкетно истраживање спроведено је на узорцима туриста у више бања у Србији. Анализа свих фактора који утичу на процес доношења одлуке о избору бања као туристичких дестинација у Србији урађена је уз помоћ аналитичко - хијерархијског процеса (АХП метод).Bearing in mind the high growth rates of spa and wellness tourism on a global level, the quantity and quality of competitive bidding has continuous growth, and in these conditions it is extremely difficult for everyone to get adequate market position. Since Serbia, despite the extremely favorable natural resources for the development of spa tourism, is still among the underdeveloped destinations, of particular importance for the future improvement of this type of tourism and positioning of spas as a tourist destination on the international tourist market is the transformation of the traditional spas in modern spa centers and wellness tourism. The main aim of the research part of this thesis is to set up a relevant scientific basis for interpretation of the transformation process of traditional spas Serbia into modern centers spa and wellness tourism; this basis must be applicable, relevant and supported by adequate theoretical framework. The task of this research was to identify the problems of development of tourism in Serbian spas, on the one hand through the analysis of the motivation of tourists who visit spas, and on the other by analyzing attributes of attractiveness spas. This thesis aims to develop a model that would encompass all the factors that influence the decision-making process of tourists when it comes to choosing the spa as a place to rest. Previous studies either included only motivation (push and pull motives) or constraints, while this study presents an integrated model that includes all three factors. Understanding and adapting to the motivation and behavior of tourists is the only way to be competitive at the spa tourism market. The survey was conducted on samples of several tourists in spas in Serbia. Analysis of all the factors that influence the decision-making process on the selection of spas as tourist destinations in Serbia was carried out with the help of Analytical - Hierarchy Process (AHP method)

Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies

Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, the capacity of peripheral vaccination to generate sustained immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Here we show using bronchoalveolar lavage samples that donors with history of both infection and vaccination have more airway mucosal SARS-CoV-2 antibodies and memory B cells than those only vaccinated. Infection also induces populations of airway spike-specific memory CD4+ and CD8+ T cells that are not expanded by vaccination alone. Airway mucosal T cells induced by infection have a distinct hierarchy of antigen specificity compared to the periphery. Spike-specific T cells persist in the lung mucosa for 7 months after the last immunising event. Thus, peripheral vaccination alone does not appear to induce durable lung mucosal immunity against SARS-CoV-2, supporting an argument for the need for vaccines targeting the airways

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice.

BACKGROUND: The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults. METHODS: Here, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice. FINDINGS: A single vaccination generates spike-specific Th1 cells, Th1-like Foxp3+ regulatory T cells, polyfunctional spike-specific CD8+ T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice. CONCLUSIONS: This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons. FUNDING: This study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection

Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1x10(2), 1x10(4), and 1x10(6) inclusion forming units (IFUs). Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4(+) and CD8(+) cells within guinea pigs' submandibular lymph node (SMLN) lymphocytes while the higher doses increased the percentages of CD4(+) and CD8(+) cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4(+) and CD8(+) cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1x10(4), and 1x10(6) IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections

Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: implications for calcification-related chronic inflammatory diseases

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and gamma-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein gamma-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNF alpha, IL-1 beta and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application.Portuguese Science and Technology Foundation (FCT) [PTDC/SAU-ORG/117266/2010, PTDC/BIM-MEC/1168/2012, UID/Multi/ 04326/2013]; FCT fellowships [SFRH/BPD/70277/2010, SFRH/BD/111824/2015

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response

Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers

Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response