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M. Sartelli, D. Weber, E. Ruppé, M. Bassetti, B. Wright, L. Ansaloni, F. Catena, F. Coccolini et al.

The original article [1] contains an error whereby a co-author, Boris Sakakushev has their family name spelt incorrectly as 'Sakakhushev'. The authors would therefore like it known that the correct spelling of the family name is 'Sakakushev'.

R. Bugiardini, B. Ricci, E. Cenko, Z. Vasiljevic, S. Kedev, G. Davidović, M. Zdravković, D. Miličić et al.

Background Women with ST‐segment–elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex‐related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS‐TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time‐delay cohorts. We estimated the 30‐day risk of all‐cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130–776] versus 240 minutes [range: 120–600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30‐day mortality (odds ratio: 1.58; 95% confidence interval, 1.27–1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29–2.02). Conclusions Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01218776.

E. Zerem, P. Jovanovic, Mirza Omerović, Dženan Jahić, Dina Zerem, Omar Zerem

Vitamin supplementation: what the gastroenterologist needs to know. J Clin Gastroenterol. 2004;38:844–854. 19. Holt PR, Bresalier RS, Ma CK, et al. Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa. Cancer. 2006;106: 287–296. 20. Fedirko V, Bostick RM, Flanders WD, et al. Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial. Cancer Prev Res (Phila). 2009;2:213–223. 21. Grau MV, Baron JA, Sandler RS, et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst. 2003;95:1765–1771. 22. Kampman E, Giovannucci E, van’t Veer P, et al. Calcium, vitamin D, dairy foods, and the occurrence of colorectal adenomas among men and women in two prospective studies. Am J Epidemiol. 1994;139:16–29. 23. Levine AJ, Harper JM, Ervin CM, et al. Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma risk. Nutr Cancer. 2001;39:35–41. 24. Irving AA, Plum LA, Blaser WJ, et al. Cholecalciferol or 25-hydroxycholeCalciferol neither prevents nor treats adenomas in a rat model of familial colon cancer. J Nutr. 2015;145:291–298. 25. Matusiak D, Benya RV. CYP27A1 and CYP24 expression as a function of malignant transformation in the colon. J Histochem Cytochem. 2007;55: 1257–1264. 26. Egan JB, Thompson PA, Ashbeck EL, et al. Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence. Cancer Res. 2010;70:1496–1504. 27. Jacobs ET, Hibler EA, Lance P, et al. Association between circulating concentrations of 25(OH)D and colorectaladenoma: a pooled analysis. Int J Cancer. 2013;133:2980–2988. 28. Kesse E, Boutron-Ruault MC, Norat T, et al. Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3NEPIC prospective study. Int J Cancer. 2005;117:137–144. 29. Boyapati SM, Bostick RM, McGlynn KA, et al. Calcium, vitamin D, and risk for colorectal adenoma: dependency on vitamin Dreceptor BsmI polymorphism and nonsteroidal anti-inflammatory drug use? Cancer Epidemiol Biomarkers Prev. 2003;12:631–637. 30. Terry P, Baron JA, Bergkvist L, et al. Dietary calcium and vitamin D intake and risk of colorectal cancer: a prospective cohort study in women. Nutr Cancer. 2002;43:39–46. 31. Wu K, Willett WC, Fuchs CS, et al. Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst. 2002;94:437–446. 32. Huerta S, Irwin RW, Heber D, et al. 1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse. Cancer Res. 2002;62:741–746. 33. Newmark HL, Yang K, Lipkin M, et al. A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis. 2001;22:1871–1875. 34. Bostick RM. Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms. J Steroid Biochem Mol Biol. 2015;148:86–95. 35. Fedirko V, Bostick RM, Flanders WD, et al. Effects of vitamin D and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2009;18:2933–2941. 36. Mart ̌ ǐńez ME. Primary prevention of colorectal cancer: lifestyle, nutrition, exercise. Recent Results Cancer Res. 2005;166:177–211. 37. Holt PR. New insights into calcium, dairy and colon cancer. World J Gastroenterol. 2008;14:4429–4433. 38. Boutron MC, Faivre J, Marteau P, et al. Calcium, phosphorus, vitamin D, dairy products and colorectalcarcinogenesis: a French case-control study. Br J Cancer. 1996;74:145–151.

Sandra Vegar - Zubović, Spomenka Kristić, B. Hadžihasanović

Aim The aim of this study is to investigate the possibilities of non-invasive diagnostic imaging methods, positron emission tomography/computed tomography (PET/CT) and CT, in clinical N staging of non-small cell lung cancer (NSCLC). Methods Retrospective clinical study included 50 patients with diagnosed NSCLC who have undergone PET/CT for the purpose of disease staging. The International association for the study of lung cancer (IASLC) nodal mapping system was used for analysis of nodal disease. Data regarding CT N-staging and PET/CT Nstaging were recorded. Two methods were compared using χ2 test and Spearman rank correlation coefficient. Results Statistical analysis showed that although there were some differences in determining the N stage between CT and PET/CT, these methods were in significant correlation. CT and PET/CT findings established the same N stage in 74% of the patients. In five patients based on PET/CT findings the staging was changed from operable to inoperable, while in four patients staging was changed from inoperable to operable. Conclusion PET/CT and CT are noninvasive methods that can be reliably used for N staging of NSCLC.

L. Z. R. Sanchez, Marija Glisic, L. Pletsch, O. Rueda-Ochoa, L. E. Echeverría, W. Bramer, A. Bano, N. Stringa et al.

Introduction: Major advancements in DNA sequencing methods introduced in the first decade of the new millennium initiated a rapid expansion of sequencing studies, which yielded a tremendous amount of DNA sequence data, including whole sequenced genomes of various species, including plants. A set of novel sequencing platforms, often collectively named as “next-generation sequencing” (NGS) completely transformed the life sciences, by allowing extensive throughput, while greatly reducing the necessary time, labor and cost of any sequencing endeavor. Purpose: of this paper is to present an overview NGS platforms used to produce the current compendium of published draft genomes of various plants, namely the Roche/454, ABI/SOLiD, and Solexa/Illumina, and to determine the most frequently used platform for the whole genome sequencing of plants in light of genotypization of immortelle plant. Materials and methods: 45 papers were selected (with 47 presented plant genome draft sequences), and utilized sequencing techniques and NGS platforms (Roche/454, ABI/SOLiD and Illumina/Solexa) in selected papers were determined. Subsequently, frequency of usage of each platform or combination of platforms was calculated. Results: Illumina/Solexa platforms are by used either as sole sequencing tool in 40.42% of published genomes, or in combination with other platforms - additional 48.94% of published genomes, followed by Roche/454 platforms, used in combination with traditional Sanger sequencing method (10.64%), and never as a sole tool. ABI/SOLiD was only used in combination with Illumina/Solexa and Roche/454 in 4.25% of publications. Conclusions: Illumina/Solexa platforms are by far most preferred by researchers, most probably due to most affordable sequencing costs. Taking into consideration the current economic situation in the Balkans region, Illumina Solexa is the best (if not the only) platform choice if the sequencing of immortelle plant (Helichrysium arenarium) is to be performed by the researchers in this region.

The urban space unites two parallel dimensions in its substance - the inner human one and the real physical one. While interpreting this thesis, we proceed from the semiotic perspective via an analysis of the source of the town's semiotics by approaches which allow creation of a global basis of pertinence in the comprehension of the urban space as a context which unites reality and ideas. In that way, searching for their place and function in the system of symbols, that is, determining the elements which make the semiotic structure of the town and influence man's perception of material environment is the main task of this paper. The analysis has shown that the presence of urban signs leaves its spatial imprint on the authentic identity of the physical structure, but that there are also contemplative elements which found the notion of town. What we are talking about here are the lifestyle, culture, tradition, social relations, politics, ideology, technical praxis, technological achievements, economic trends, social practices. It is precisely the synergy impacts of these elements and geometric appearances of the physical structure that, as we have concluded, make the semiotic structure of the urban space. Man perceives this synergy by means of strength of his own being, while articulations of the functional spaces and signs of the town's architecture, each of them marked by their inner energy, enable him to reassert himself as a spiritual being. We are convinced that the approach to the reflections about the urban space semiotics that has been shown in this paper, can make a contribution to the understanding of the general urban experience, as well as a contribution to the general theory of urban design.

N. Bešlić, Sabrina Licina, Amera Sadija, R. Milardović

Introduction: Consensus hasn’t been yet achieved about optimal dose quantity that could prevent post therapy hypothyroidism, thus dosing approach varies among different centers. I131 doses can be fixed or calculated, although treatment outcomes don’t differ significantly according to recent acknowledgments. Aim: Determination of the incidence of hypothyroidism after radioiodine treatment (I131) in dependence of hyperthyroidism etiology and quantity of applied doses. Materials and methods: The study included 100 patients which have had radioiodine treatment, with a three year post-treatment follow up. The study was conducted at the Nuclear Medicine Department, University Clinical Center of Sarajevo. Data were provided from the patient medical histories. Research is designed as a retrospective, descriptive study. All data were analyzed using Microsoft Excel and the statistical program SPSS 13.0. Results: After the three year follow up, incidence of hypothyroidism within patients with Graves’ disease was 89.5%, with diffuse goiter 50%, with toxic adenoma (TA) 26.8%, and with multinodulare goitre (MNG) 57.1%. Hypothyreoidism in patients with diffuse goiter, Graves’ disease and TA was mostly developed after I131 therapy with a dose quantity of 10.1-15 mCi and in MNG patients after RAI therapy with applied doses of 15.1-20 mCi. Conclusion: The hypothyroidism incidence rate is the highest among patients with Graves’ diseases and the lowest among the TA patients. It’s mostly developed after dose quantity of 10.1-15mCi and it is rare at dose quantity less than 5mCi. 50% of hypothyroidism were developed among patients with diffuse goiter, Graves’disease.

Aim To analyse the long-term impact of altered metabolism on the level of mediators of inflammatory response in female patients with type 2 diabetes. Methods This study included 97 female patients with type 2 diabetes and 107 female, nondiabetic control subjects, who were recruited at the Clinical Centre University of Sarajevo and the General Hospital Tešanj. The effects of glycaemic control on markers of inflammatory response represented by C-reactive protein (CRP), fibrinogen, leukocytes, sedimentation rate, and cytokine IL-6 were tested. All subjects were free of evidence of infections, surgery, thyroid disease, polycystic ovarian syndrome, active liver and kidney damage. All biochemical analyses were performed according to standard International Federation of Clinical Chemistry (IFCC) protocols. Results A significant increase of fibrinogen (p<0.001), CRP (p=0.001), interleukin-6 (p=0.013), leukocytes (p<0.001) and sedimentation rate (p=0.008) in diabetic female population compared to control subjects was found. A significant correlation between CRP and haemoglobin A1c (p=0.035), interleukin-6 and glucose (p=0.032), IL-6 and body mass index (p=0.007) was found. Conclusion Our data suggest that inflammation plays an important role in the pathogenesis of diabetes in female diabetic population. A more detailed study on a far larger number of subjects is needed if they were to be used effectively as biomarkers in the primary prevention of type 2 diabetes in this population.

Aim To determine the serum levels of matrix metalloproteinase 9 (MMP-9) concentration and their association with the stage and histopathologic sizes of colorectal cancer (CRC). Methods One hundred and two patients with clinically diagnosed and histologically confirmed colorectal cancer ready for surgical treatment were included in the study. In each patient, preoperative peripheral venous blood samples were taken for determination of the concentration of MMP-9 using ELISA immunoassay test. Resected tumour specimens were studied pathologically according to the criteria of the TNM classification. All patients were divided into groups according to the TNM classification. The control group presented 30 subjects of the appropriate age and gender with no family history of cancer, clinical signs of malignancy or inflammatory bowel disease. Results The serum levels of MMP-9 were progressively increased in patients with CRC reaching the highest value in the fourth stage of CRC. It was also confirmed that the serum concentrations of MMP-9 were significantly higher in patients with pericolonic lymph nodes involvement compared to the patients with no involvement of lymph nodes, 456.4 (445.9-464.7) ng/mL vs. 438.4 (418.4-447.8) ng/mL (p<0.001). Significantly higher serum levels of MMP-9 were found in the patients with metastatic CRC, 458.5 (452.0-468.1) ng/mL compared with the CRC patients without metastasis, 445.8 (436.9-456.5) ng/mL (p<0.001). Conclusion It was confirmed that serum concentration of MMP-9 presented the significant independent risk factors for the progression of CRC.

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