The contemporary demographic development of Bosnia and Herzegovina is a very active topic in academic, but also in wider political and public discourses, particularly in the context of increased depopulation trends. Distinctly negative processes in the natural change and net migration are the result of post-war and transitional circumstances, as well as the socio-economic status of the country. Demographic disparities conditioned by a complex social background (economic, social, political, cultural and environmental factors) are often the subject of geographic research in this area, however, few studies have resulted in a comprehensive demographic categorization of municipalities and cities in Bosnia and Herzegovina, which would be the first step in detection precise causes of demographic regression. Demographic categorization of municipalities on the basis of as many available demographic indicators as possible is a useful instrument in planning, through which concrete revitalization measures can be created primarily aimed at reducing polarization effects in development and depopulation of continuously deprived regions. This study used demographic data from the last 2013 population census, as well as those from more recent publications of national and entity statistical agencies. Special focus is placed on the index of total population change, population density, vital index, ageing coefficient and share of highly educated population. These indicators were analysed from the aspect of regional disparities, whereby special categories of municipalities and cities were created for each of them, in relation to how favourable is local demographic situation. In the second phase, their multi-criteria data integration was carried out, which more clearly indicate the general level of demographic development of individual municipalities/cities.

This paper analyses the statistical parameters that give a comprehensive overview of the socio-demographic state of the border areas of Bosnia and Herzegovina, and it represents a novel attempt to examine the disparity and relationships between central and peripheral parts of national territory. The methodology is based on examining the differences between border and non-border municipalities/cities according to four groups of indicators, to obtain four indices: depopulation, natural change, ageing and education. Statistically significant differences were found primarily in the context of population age structure, and it can be concluded that the ageing process has affected bordering regions more than the rest of the country.

Sarajevo is a very interesting tourist destination. The official statistics of Canton Sarajevo show that tourists usually visit Sarajevo individually. The purpose of this paper is to explore the differences between foreign tourists who came to Sarajevo individually and the ones whose travel was organized by a travel agency. The aim of this research is to compare foreign tourists from the aspect of the travel mode in relation to the declaration of tourists' satisfaction with a tourist destination, the general quality of this tourist destination offer, overall satisfaction, and loyalty. For the purposes of data analysis, descriptive statistics and Mann–Whitney U test were used. The results have shown that foreign tourists who visited Sarajevo individually have a more positive attitude about perceived value, declaration of tourists' satisfaction with a tourist destination, and they are more willing to revisit Sarajevo in the future than the foreign tourists who visited through a travel agency / another organizer. Also, it has been shown that there is no statistically significant difference between visitors who visited Sarajevo individually and tourists who visited through a travel agency / another organizer in terms of the general quality of the tourist destination offer, overall satisfaction, and intention to recommend Sarajevo to their friends and relatives.

Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of “unwanted-self” components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma. Despite its tumor-promoting role in mouse models of melanoma and lymphoma the expression and functional role of stabilin-1 in breast cancer was unknown. Here, we demonstrate that stabilin-1 is expressed on TAM in human breast cancer, and its expression is most pronounced on stage I disease. Using stabilin-1 knockout (ko) mice we show that stabilin-1 facilitates growth of mouse TS/A mammary adenocarcinoma. Endocytosis assay on stabilin-1 ko TAM demonstrated impaired clearance of stabilin-1 ligands including SPARC that was capable of inducing cell death in TS/A cells. Affymetrix microarray analysis on purified TAM and reporter assays in stabilin-1 expressing cell lines demonstrated no influence of stabilin-1 expression on intracellular signalling. Our results suggest stabilin-1 mediated silent clearance of extracellular tumor growth-inhibiting factors (e.g. SPARC) as a mechanism of stabilin-1 induced tumor growth. Silent clearance function of stabilin-1 makes it an attractive candidate for delivery of immunomodulatory anti-cancer therapeutic drugs to TAM.

Tumor-associated macrophages (TAM) are crucial participants in malignant progression. Acquisition of M2 (alternatively activated) phenotype by TAM during tumor progression enhances the immunosuppressive and tumor-supportive properties of TAM resulting in tumor invasion, metastasis and angiogenesis. Previously we have found that stabilin-1, a multifunctional scavenger/sorting receptor, is a marker of M2 macrophages that is expressed by TAM in several murine tumor models. However, its role in tumor progression was not defined. In order to identify the role of stabilin-1 in tumor progression, the model of mammary adenocarcinoma (TS/A) was established in BALB/c mice with stabilin-1 knockout. The growth of TS/A mammary adenocarcinoma in stabilin-1 knockout (ko) mice was suppressed by 36%. To identify the role of stabilin-1 in TAM biology and reveal functions of stabilin-1 that are important for tumor progression, isolation of high purity TAM from TS/A murine adenocarcinoma was established and optimized. Flow cytometry analysis revealed that adhesion/internalisation of extracellular SPARC was decreased in the isolated stabilin-1 ko TAM compared to wt TAM. Immunofluorescent/confocal microscopy showed that transport of SPARC into the endocytic pathway was significantly impaired in the stabilin-1 ko TAM. Since SPARC is known to inhibit the development of solid tumors including breast cancer we hypothesize that knockout of stabilin-1 in TAM induces accumulation of extracellular SPARC resulting in suppression of tumor growth. Analysis of two cohorts of female patients with breast carcinoma of different stages demonstrated that stabilin-1 is expressed on significant part of tumor associated macrophages. Three types of TAM were identified by co-staining with anti-stabilin-1 RS1 antibody and anti-CD68 antibody: CD68+stabilin-1-, CD68+stabilin-1+ and CD68-stabilin-1+. The highest levels of stabilin-1 expression and highest amount of stabilin-1+ TAM were found on stages I and IIa, suggesting that stabilin-1 is required for tumor growth at early stages of tumor progression. Our data indicate that stabilin-1 expression on TAM is necessary on the early stages of tumor growth in human cancer. Genetic knockout of stabilin-1 results in decrease in tumor growth in mouse adenocarcinoma model. In addition, tumor-associated macrophages deficient in stabilin-1 expression have significantly decreased ability for the endocytic clearance of SPARC. Citation Format: Vladimir Ryabov, Ilja Ovsij, Aida Avdic, Kai Schledzewski, Alexei Gratchev, Nan Wang, Bernd Arnold, Sergij Goerdt, Frederick Pfister, Alexander Marx, Limin Zheng, Julia Kzhyshkowska. Stabilin-1 is expressed on tumor-associated macrophages in breast cancer and supports tumor growth in animal model of breast adenocarcinoma by clearance of SPARC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1668. doi:10.1158/1538-7445.AM2014-1668

BACKGROUND & AIMS Gastrointestinal (GI) and liver diseases inflict a heavy economic burden. Although the burden is considerable, current and accessible information on the prevalence, morbidity, and cost is sparse. This study was undertaken to estimate the economic burden of GI and liver disease in the United States for use by policy makers, health care providers, and the public. METHODS Data were extracted from a number of publicly available and proprietary national databases to determine the prevalence, direct costs, and indirect costs for 17 selected GI and liver diseases. Indirect cost calculations were purposefully very conservative. These costs were compared with National Institutes of Health (NIH) research expenditures for selected GI and liver diseases. RESULTS The most prevalent diseases were non-food-borne gastroenteritis (135 million cases/year), food-borne illness (76 million), gastroesophageal reflux disease (GERD; 19 million), and irritable bowel syndrome (IBS; 15 million). The disease with the highest annual direct costs in the United States was GERD ($9.3 billion), followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion), and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17 diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of $22.8 billion. The estimated direct costs for all digestive diseases were $85.5 billion. Total NIH research expenditures were $676 million in 2000. CONCLUSIONS GI and liver diseases exact heavy economic and social costs in the United States. Understanding the prevalence and costs of these diseases is important to help set priorities to reduce the burden of illness.