The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation of three polycyclic aromatic hydrocarbons (PAHs) in a panel of isogenic colorectal HCT116 cells with differing TP53 status. Cells that were TP53(+/+), TP53(+/−), TP53(−/−), TP53(R248W/+) or TP53(R248W/−) were treated with benzo[a]pyrene (BaP), dibenz[a,h]anthracene and dibenzo[a,l]pyrene, and the formation of DNA adducts was measured by 32P-postlabelling analysis. Each PAH formed significantly higher DNA adduct levels in TP53(+/+) cells than in the other cell lines. There were also significantly lower levels of PAH metabolites in the culture media of these other cell lines. Bypass of the need for metabolic activation by treating cells with the corresponding reactive PAH-diol-epoxide metabolites resulted in similar adduct levels in all cell lines, which confirms that the influence of p53 is on the metabolism of the parent PAHs. Western blotting showed that CYP1A1 protein expression was induced to much greater extent in TP53(+/+) cells than in the other cell lines. CYP1A1 is inducible via the aryl hydrocarbon receptor (AHR), but we did not find that expression of AHR was dependent on p53; rather, we found that BaP-induced CYP1A1 expression was regulated through p53 binding to a p53 response element in the CYP1A1 promoter region, thereby enhancing its transcription. This study demonstrates a new pathway for CYP1A1 induction by environmental PAHs and reveals an emerging role for p53 in xenobiotic metabolism.

The aim of this study was to look for any secular trend in the stature of Balkan populations from the time of World War II (1939-1945) to the Balkans War (1991-1995). The research was based on the examination of exhumed skeletons of 202 men killed in World War II in the area of the Republic of Slovenia, and 243 men killed in the Bosnian War in Bosnia and Herzegovina. The length measurements of the right and left humerus, femur, tibia and fibula were taken. Since the results revealed no significant differences and the left-sided bones were more complete and recurrent in the sample, the bones of the left side were used in the analysis. Since the increase in height depends mostly on the increase in length of the long bones, with an average absolute change of about 0.28 cm for humerus, 0.55 cm for femur, 0.49 cm for tibia and 0.20 cm for fibula per decade in our case, these results suggest a significant increase of the height of the Balkans population. The difference of the sum of the average femur and tibia length for the study period was 4.13 cm. Recalculated average length increase of the sum length of femur and tibia per decade was 0.88 cm for the left side. Our study revealed that there was a trend towards increased long bone lengths, at least in the male population analyzed.

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

The Serbian aggression against the Republic of Bosnia and Herzegovina from 1992 to 1995, was marked with heavy sufferings of the non-Serb population, i.e. with genocide. The intensity and methods of its implementation depended on the demographic image on the field, that is to say on Serb plans towards the possible division of Bosnia and Herzegovina according to the national criterion. The possibility of realization depended on the organization and strength of the aggressor, but also of the defenders. The Bosnian Frontier region (Bosanska Krajina) is a significant example of the Serb genocide committed against Bosniaks and Croats in Bosnia and Herzegovina. On the example of Prijedor, the author presents his results in research of sufferings of the Bosniak and Croat population and proves the violent creation of the long term Serb predominance and demographic changes caused by genocide.

Based on available sources and literature, the author considers the frequency of female names in medieval Bosnia. With further analysis, he answers the question to what extent did the social rank of a person influence the giving of the name and he also compares the frequency of female names in different geographic regions of medieval Bosnia. The paper also reconstructs the question of giving names to women belonging to various religious groups.

Objective: It is well known that coronary artery bypass grafting (CABG) is often the cause of non-thyroidal illness syndrome (NTIS). Nonthyroidal illness syndrome (NTIS) is a state characterized by low levels of tri-iodo-thyronine (T3) and high levels of reverse T3 (rT3), with normal or low levels of thyroxin (T4) and normal, low-normal, or low levels of thyroid-stimulating hormone (TSH). Today, there are two main techniques of CABG: CABG with the use of cardiopulmonary bypass (on-pump coronary artery bypass - ONCAB) and CABG without the use of cardiopulmonary bypass (off-pump coronary artery bypass OPCAB), or ’beating-heart surgery.’ The OPCAB technique is considered to be less invasive. We prospectively investigated the influence of these surgical techniques on the occurrence of NTIS. Methods: Serum levels of free fractions of thyroid hormones (FT3 and FT4) and TSH were analyzed in 70 consecutive patients subjected to CABG surgery, using the ONCAB technique in 36 patients and OPCAB technique in 34 patients. The measurements of hormone levels were performed prior to surgery and 12 hours and 14 days after surgery. Results: The basic, the early, and the late postoperative serum levels of FT3 (p=0.458, p=0.632, p=0.869, respectively), FT4 (p=0.664, p=0.301, p=0.417, respectively), and TSH (p=0.249, p=0.058, p=0.324, respectively) were similar in both groups. The levels of FT3 and TSH were significantly lower 12 hours after surgery (p<0.0001, p<0.0001, respectively), and the FT4 levels rose at the same time (p<0.0001). The third measurement showed the return of all investigated parameters back to physiological levels, although they were still not precisely within the initial values. Conclusion: NTIS occurs significantly in patients subjected to CABG. Although the OPCAB technique is considered to be less invasive, its impact on the occurrence of NTIS does not differ significantly from the ONCAB technique.