Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloSCT). In GVHD, donor T cells recognize recipient tissues as non-self and mount a broad attack that results in multi-organ damage. While there has been some success in diminishing the incidence of GVHD, less progress has been made in treating established or steroid-refractory disease without severe global immunosuppression. This is in part due to a lack of understanding of the underlining mechanisms that sustain GVHD despite chronic T cell antigen exposure. To address this, we developed a mouse GVHD model that allows us to track the progeny of single alloreactive T cell clones. We used this model to test hypotheses on GVHD maintenance: 1) GVHD is driven by the continuous output and trafficking of alloreactive T cells from secondary lymphoid tissues (SLT) into GVHD target organs; and 2) once tissues are seeded with alloreactive T cells from SLT, GVHD is maintained locally within affected tissues. We reasoned that if GVHD is maintained by the continuous SLT output of T cells, the progeny of single alloreactive clones in a target tissue would come into equilibrium with those in SLT and other target tissues. Alternatively, if there is a degree of local tissue GVHD maintenance, our model predicts that clonal progeny should be unequally distributed and not in equilibrium with SLT. We first tested these possibilities using a GVHD model wherein BALB/c RAG2-/- TCR transgenic (Tg) CD4 T cells (TS1) that recognize the S1 peptide derived from influenza hemagglutinin (HA) induce GVHD in BALB/c RAG2-/- mice that ubiquitously express HA (HA104 mice). We generated TS1 TCR Tg mice on 9 congenic backgrounds based on the expression of CD45.1/2, Thy1.1/2 and GFP. We transferred 500 naïve TS1 cells of 1 clonotype (to induce GVHD) along with single naïve TS1 cells from the remaining 8 clonotypes and BALB/c RAG2-/- bone marrow (BM) into lethally irradiated HA104 mice. We recovered a total of 432 single-cell derived TS1 clones (72% of input clones) from tissues of 79 mice, analyzed 7-35 days after transfer. We enumerated the TS1 clonal composition of each tissue (expressed as the % of all TS1 of that tissue) and found disparate clonal distribution across tissues within individual mice. For example, in a representative mouse analyzed at day 33 (Figure 1), the fractions of a single TS1 clone were relatively high in the colon (1.4%) and small intestine intraepithelial lymphocyte (IEL) (4.6%) when compared to the spleen (0.07%), BM (0.02%) and liver (0.03%). These data support that TS1 clones are not equally distributed among tissues and are not in equilibrium with SLT, suggesting that GVHD is at least in part maintained locally. We also analyzed TS1 clonal frequency distribution in a second model. BALB/c RAG2-/- BM and polyclonal T cells were transplanted into F1 (BALB/c HA104xB10.D2) recipients along with 8 single distinct TS1 cells. In this system, GVHD is induced by polyclonal BALB/c cells and TS1 cells are trackers of reactivity to HA. Preliminary experiments also indicate unequal distributions of TS1 clones across tissues in individual mice. In a second approach to test whether GVHD is maintained locally, irradiated HA104 mice were reconstituted with either 500 Thy1.1 or 500 Thy1.2 TS1 cells and CD45.1 or CD45.2 BALB/c RAG2-/- BM. One partner also received congenic TS1 single cells. We performed parabiosis of mice from one group to the other 21-28 days later. We analyzed 4 pairs 4 weeks post-joining, looking first at the blood to establish a baseline for TS1 crossover from the parabiotic partner. In blood, 18.9% ±1.9 of all TS1 were derived from the partner. Importantly, relative to equilibration in blood, there were far fewer partner-derived TS1 cells in all other tissues (Figure 2). Only a few single cell-derived TS1 clones were detected in the partner mouse at very low frequencies, even when they were dominant in tissues of the corresponding partner. Together, these data indicate that once GVHD is established, local maintenance dominates over new TS1 entry. Consistent with this, TS1 cells incorporate BrdU in vivo even at late time points. We are combining proliferation and clonality data at multiple timepoints to develop a mathematical model of GVHD establishment and maintenance. We are also extending our observations in a polyclonal GVHD model wherein the progeny from single alloreactive CD8 cells can be enumerated. Shlomchik: NapaJen: Consultancy.

The aim of this work was to perform the phytochemical analysis as well as antioxidant and anticholinesterase potential of hot water and methanolic extracts from Mentha pulegium L., Lamiaceae, wild growing in Bosnia and Herzegovina. It is a plant that is traditionally used in Bosnia and Herzegovina medicine to treat gastrointestinal and neurological disorders. By HPLC‐DAD analysis of tested extracts, 15 phenol compounds were identified and quantified. Rosmarinic acid was the most abundant compound in both extracts, followed by ellagic acid, eriodictyol, naringenin and chlorogenic acid. Both extracts were demonstrated good radical scavenging potential, reducing power and ability to inhibit lipid oxidation. The tested extracts also showed low ability to inhibit protein oxidation and low or no acetylcholinesterase and butyrylcholinesterase inhibition potential. The promising radical scavenging potential, reducing power and lipid protection potential of tested extracts indicates that the extracts of M. pulegium could be useful in preventing free radical linked diseases, as well as food protecting antioxidants.

The purposes of this study were (I) to examine which game-related statistics can serve to discriminate between winning and losing teams according to final game outcome in NLB League basketball, and (II) to determine the differences in game-related statistics for teams who play in the NLB League and EuroLeague when they win and lose in two competitions. The game-related statistics that were analyzed are 2- and 3-point field-goals (both successful and unsuccessful), free-throws (both successful and unsuccessful), defensive and offensive rebounds, assists, turnovers, steals, blocks made, blocks received, fouls committed and fouls received. Results of the discriminant analysis showed that winning teams differ from losing teams in assists (SC=0.417), defensive rebounds (SC=0.399) and in successful 2-point (SC=0.355) and 3-point field goals (SC=0.325). In balanced games winning differ from losing teams in defensive rebounds (SC=0.388), successful 2-point field goals (SC=0.343) and blocks committed (SC=0.303), and in unbalanced games winners were better in assists (SC=0.434), defensive rebounds (SC=0.304) and successful 3-point field goals (SC=0.353). When the  teams Partizan, Olimpija and Cibona played in the NLB League, the difference between wins and losses was in assists (SC=0.395), successful 2-point field goal attempts (SC=0.371) and defensive rebounds (SC=0.326). When they played in the EuroLeague, the difference was only in unsuccessful 2-point field goal attempts (SC=0.414) and blocks received (SC=0.318). Data obtained in this study may be useful for coaches in preparing their teams and analyzing opponents during preparations for competitions.

This study aimed to examine: (i) the level of physical activity (PA), obesity indices and cardiorespiratory fitness (CRF) among boys and girls in primary school, and (ii) to determine the association of obesity indices and PA with CRF for the total number of participants, and then separately for boys and girls. 753 sixth to ninth grade girls and boys aged 10–14 years took part in this cross-sectional study. The PA was assessed by the “Physical Activity Questionnaire – Children” and CRF was assessed by the Maximal multistage a 20 m shuttle run test. Body mass index (BMI), waist circumferences (WC), and waist to height ratio (WHtR) were considered as obesity indices. Multiple linear regression analyses were performed to explore correlates of CRF. The results obtained showed the prevalence of general overweight and obesity was 25.5% in our sample which was lower than that in the regional estimate (e.g., ∼28%) for Eastern Europe. Among all participants, CRF was associated with male sex, older age, a lower WC percentile, higher WHtR, and higher level of PA. The model accounted for 24% of the variance. CRF was associated with older age and higher level of PA among girls and boys. Lower WC percentile was a significant determinant of CRF among boys. In conclusion, general overweight/obesity was not independently associated with CRF. Those with better CRF were more likely to be male and older, had a higher level of PA and lower central adiposity. These findings emphasize the importance of supporting school age children to take a part in programmed physical activity regardless of their body composition.

Sport participation is considered as a factor of potential influence on illicit drug misuse (IDM) in adolescence, but there is an evident lack of studies which prospectively investigated this problem. This study aimed to prospectively investigate the sports-related factors related to IDM and the initiation of IDM among older adolescents. The participants were 436 adolescents (202 females; 16 years old at study baseline). They were tested at baseline and follow-up (two years later). The predictors included variables associated with different facets of sports participation and success in sports. The criteria were (i) baseline IDM, (ii) follow-up IDM, and (iii) initiation of IDM between baseline and follow-up. Crude and adjusted (controlled for parental conflict, age, socioeconomic status, and gender) logistic regressions were applied to establish correlations between predictors and criteria. There were higher odds for baseline IDM in adolescents who quit individual sports (OR: 4.2, 95% CI: 1.3-13.9), who had better competitive sports achievements (OR: 1.8, 95% CI: 1.0-3.3), and those involved in sports for a longer time (OR: 1.6, 95% CI: 1.0-2.5). The IDM at follow-up was more prevalent in adolescents who were involved in sports for a longer time (OR: 1.7, 95% CI: 1.1-2.6). Initiation of drug use was predicted by longer experience in sports (OR: 1.8, 95% CI: 1.1-3.1). Sports-related factors were more negatively than positively related to illicit drug use. Most probably, the transition from junior to senior level in sports put specific stress on those adolescents who were highly committed to sports until that time, but who then had to question their own sports abilities and future potential in sports. Sport-authorities should be informed on established results and specific public-health efforts aimed at preventing IDM in athletic adolescents are urgently needed.

The research was carried out on a sample consisting of the members of the Special Brigade of the Serbian Armed Forces, members of the 63rd Parachute Battalion. A total of 100 participants took part in the study, of an average age of  30±0,5 yrs. The subject matter of this paper are their body composition and specific fitness abilities. The aim of the paper was to determine the correlation between body composition and specific fitness abilities, as well as to determine the cross-correlation between the parameters of body composition and specific fitness abilities. A canonical correlation analysis was used to determine the connection between the set of predictor variables and the criterion variable. Based on the obtained results it could be concluded that there is a significant correlation (p= .010) between body composition and fitness abilities. It can be concluded that the excess of fat tissue (BF%, BFkg, index visceral BF) and BMI have a negative effect on fitness, while a greater amount of muscle mass (MM% and MMkg) has a positive influence on fitness. The results indicate that participants who do not have as many layers of fat have better values for repetitive power of the abdominal muscles, and that the percentage of muscle mass has a positive effect on the repetitive power of the pectoral muscles, muscles of the arms and abdomen.

Computational geometry is an integral part of mathematics and computer science deals with the algorithmic solution of geometry problems. From the beginning to today, computer geometry links different areas of science and techniques, such as the theory of algorithms, combinatorial and Euclidean geometry, but including data structures and optimization. Today, computational geometry has a great deal of application in computer graphics, geometric modeling, computer vision, and geodesic path, motion planning and parallel computing. The complex calculations and theories in the field of geometry are long time studied and developed, but from the aspect of application in modern information technologies they still are in the beginning. In this research is given the applications of computational geometry in polygon triangulation, manufacturing of objects with molds, point location, and robot motion planning.