32 results on '"Gacic J"'
Search Results
2. World Wide Web e melanoma register: myth or reality: P066
- Author
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Nikolic, D. V., Nikolic, A. T., Stanimirovic, V. V., and Gacic, J.
- Published
- 2014
3. Benefit of using dermoscopy in revealing thin melanomas in Southestern Europe: P065
- Author
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Nikolic, D. V., Nikolic, A. T., Stanimirovic, V. V., and Gacic, J.
- Published
- 2014
4. Gender differences in stress intensity and coping strategies among students, future emergency relief specialists
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Gačić Jasmina, Jović Slađana J., Terzić Negra S., Cvetković Vladimir M., Terzić Miloš T., Stojanović Dušan G., and Stojanović Goran R.
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sex factors ,stress, psychological ,students ,surveys and questionnaires ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Assisting students face high academic demands which, together with interpersonal, intrapersonal and professional requirements, can be a significant source of stress. The aim of the study was to examine the intensity and frequency of the source of stress, coping strategies and identify gender differences among students, future assisting professionals. Methods. An observational, cross-sectional study was conducted amongst the students of the University of the Belgrade Faculty of Security (Serbia) who, after graduation, will acquire the title of a security manager responsible for human resources in the civil sector. The data were collected in the period October-November 2018. The authorized questionnaire SSM-30 by Jović (Stress scale for the young – 30) was used, which enables students to assess the stress situations intensity on a scale from 1 (minimum) to 10 (maximum intensity). The SSM-30 questionnaire is a combination of the standard Life Events Scale – Holmes Rashe Life Events Scale, also known as the Social Readjustment Rating Scale and life events characteristic for the student population. The questionnaire also included the sample demographic characteristics – gender, and a year of study. The SSM-30 scale includes a list of stressful events and stress coping mechanisms shown in the results. Results. The most common sources of stress in both genders were social and academic ones: death in the family, critical illness in the family, an accident of a person they care about, unwanted pregnancy, lies from close people, disagreement with parents, loss of a study year, crisis, uncertainty after graduation and partner’s infidelity. The most frequently used mechanisms for controlling and overcoming stress were mostly social: talking with friends, listening to music, family support, frequent walks, socializing and going out, using the Internet, frequent sleep, intense physical activity, crying and relaxation. Statistically significant differences between the genders were confirmed – female students demonstrated self-worth of higher intensity during the majority of stressful situations, as they use different stress coping mechanisms from their male students. Conclusion. The results obtained with regard to the assessment of stressors and the use of specific mechanisms for coping point to the need of additional education of students in this field in order to be more focused and open for free professional help, when necessary.
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- 2021
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5. On the work of architect Milosav Mitić in Belgrade
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Gačić Jelena D.
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milosav mitić ,serbian post-wwii architecture ,belgrade 5 ,mihailo čanak ,novi beograd ,Architecture ,NA1-9428 - Abstract
Architect Milosav Mitić figures prominently among numerous authors who contributed to the emancipatory and artistic development of the post-WWII architecture in Serbia. Recognised even in his student years as a talented and artistically inclined author, in the years to come Mitić became a member of the renowned Belgrade 5 group, together with his colleagues Mihailo Čanak, Leonardo Lenarčić, Ivan Petrović, and Ivan Simović, submiting designs to numerous public competitions and designing major housing areas and related facilities in Novi Beograd. Although his prolific professional engagement earned him timely acknowledgement of his contemporaries, a thorough historiographic evaluation that would put the life and work of this author in the limelight for both professional and general public is still missing. That is the very reason behind this comprehensive analysis of the life and work of architect Mitić, aimed at interpreting his Belgrade oeuvre as coherently as possible.
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- 2020
6. Scientific misconduct
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Todorović Slobodan, Tošković Borislav, Čolaković Nataša, Mrda Davor, Gačić Jasna, and Todorović Tatjana
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scientific misconduct ,fabrication ,falsification ,plagiarism ,Medicine (General) ,R5-920 - Abstract
With the creation of a global computer network, the internet, all manner of information has become available to scientists and everyone else around the world. The exchange of information gives scientists insight into the most recent scientific discoveries while enabling them at the same time to use the information for their research. Scientists and experts must be sure that their colleagues' research is valid, objective and the results complete. These scientific research characteristics represent scientific honesty. Scientific misconduct can take various forms and can be present in all phases of the scientific research process, but most commonly takes the form of fabrication, falsification and plagiarism. The reasons for scientific misconduct can be personal, professional and financial. There is also a "grey zone", which consists of data manipulation and selection, reference citing mistakes, multiple and salami publications, problematic authorships. Every type of misconduct has a detrimental effect on the scientific community. In the public eye, scientists are benevolent seekers of truth with high moral integrity, whose work is of key value to society. Any type of scientific misconduct serves to dishonour the scientific community but also brings confusion into the work of other researchers, therefore significantly slowing down scientific discovery in whole. Digitalization and technological advancement significantly contribute to the early discovery, elimination and sanctioning of any kind of research misconduct. A significant improvement in solving these problems can be achieved through adequate education of young researchers and introducing laws that precisely define penalties for breaking the code of good scientific practice.
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- 2020
7. The correlation between metabolic syndrome quantification scores and numerous laboratory parameters related to this syndrome
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Srećković Branko, Mrdović Igor, Soldatović Ivan, Resan Mirko, Janeski Nenad, Čolak Emina, Janeski Hristina, Šumarac-Dumanović Mirjana, Joković Miloš, Ivanović Nebojša, Gačić Jasna, and Dimitrijević-Srećković Vesna
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biomarkers ,homocysteine ,metabolic syndrome ,risk assessment ,risk factors ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Metabolic syndrome (MS) is characterized by basic cluster risk factors – waist circumference (WC), glucoregulation disorders, hypertension, hypertriglyceridemia, low HDL-cholesterol followed by associated factors such as insulin resistance (IR), C-reactive protein (CRP), uric acid, plasminogen activator inhibitor-1 (PAI-1), fibrinogen, hyperhomocysteinemia (HHcy), nonalcoholic fatty liver disease (NAFLD) and microalbuminuira. The aim of this study was to analyze basic and associated factors of MS in patients with and without MS as well as correlation of siMS score, siMS risk score with basic and confounding factors of MS. Methods. The study included 148 overweight [body mass index (BMI) 25–30 kg/m2 and obese patients (BMI > 30 kg/m2)], age 30–75 years, classified into two groups: I – with MS (68 patients); II – without MS (80 patients). For quantification of MS, siMS score was used as a method, and siMS risk score was used as atherosclerotic complications risk indicator. Results. Patients with MS had statistically higher values of WC, hypertension, triglycerides (p < 0.001), glycemia (p = 0.006), as well as values of associated factors of MS [homeostatic model assessment (HOMA-IR)] (p = 0.002), CRP (p = 0.01), uric acid (p < 0.001), alanin transaminase (ALT) (p = 0.007) i gammaglutamyl transferase (GGT) (p = 0.001) and lower values of HDL-cholesterol (p < 0.001) compared to patients without MS. siMS score has shown correlation with associated factors of MS (log HOMA IR, logCRP, uric acid, (p < 0.001), fibrinogen (p = 0.005), liver enzymes logALT (p = 0.001) and log GGT (p < 0.001) and renal parametars (creatinine (p = 0.013) and serum protein (p = 0.006). siMS risk score correlated significantly with homocysteine, platelets, uric acid, blood urea nitrogen, albumins and proteins. Conclusion. In our study we found that patients with MS had higher values of associated factors of MS (HOMA-IR, CRP, uric acid, ALT, GGT), which was confirmed by correlation with siMS score. siMS score further indicated that IR, CRP, fibrinogen, uric acid and NAFLD are associated factors of MS. siMS risk score is another score that indicated that obesity and hyperprotein diet aggravates HHCy with age, increasing the risk for renal dysfunction and promoting atherosclerotic complications.
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- 2020
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8. Carotid intima-media thickness, 25-OH vitamin D, homocysteine and subclinical coronary artery atherosclerosis in patients with type 1 diabetes mellitus
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Milić Gordana, Gačić Jasna, Mladenović-Marković Ana, Soldatović Ivan, Matić Dragan, Popović Srđan, Marković Željko, and Damjanović Svetozar
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type 1 diabetes mellitus ,atherosclerosis ,multidetector computed tomography coronary angiography ,carotid artery ,coronary artery ,Biology (General) ,QH301-705.5 - Abstract
Individuals with type 1 diabetes have an increased risk of premature atherosclerosis. The aim of this study was to evaluate the possible predictive significance of elevated plasma total homocysteine (tHcy), lower serum 25-hydroxy vitamin D (25(OH)D) concentrations and increased carotid intima-media thickness (CIMT) for the development of coronary atherosclerosis in patients with type 1 diabetes mellitus (T1D) and no previous history of ischemic heart disease. The study included 73 patients previously diagnosed with T1D. The patients were divided into groups with and without non-obstructive moderate coronary artery stenosis. Coronary artery stenosis was examined using coronary multidetector computed tomographic angiography (MDCTA); CIMT was measured by B-mode ultrasound. The patients with moderate stenosis had significantly higher HbA1c (p
- Published
- 2019
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9. Belgrade opus of architect Jovanka Jeftanović
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Gačić Jelena
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jovanka jeftanović ,serbian post-war architecture ,belgrade ,obrenovac ,barajevo ,urbanism ,Architecture ,NA1-9428 - Abstract
Jovanka Jeftanović is one of the most significant female architects who graduated at the Faculty of Architecture of the University of Belgrade prior to 1941, and whose professional career spanned post World War II period, from 1940s to 1960s. The designs she authored in Belgrade and in the surrounding area, while working in eminent town planning and designing offices, are among her most admirable projects. Even though historiography has timely recognised her significance for the Serbian post-war architecture, her entire contribution has not been thoroughly valorised. For that reason, we take this opportunity to present the unknown facts about the life and work of architect Jeftanović with the aim of providing a comprehensive interpretation of her opus.
- Published
- 2019
10. Pre- and postoperative characteristics of metabolic syndrome in patients with colorectal cancer
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Gačić Jasna, Dimitrijević-Srećković Vesna, Gačić Dragan, Petričević Simona, Srećković Branko, Lazić Bratislav, Đorđević Aleksandar, Đukanović Blagoje, and Ranđelović Tomislav
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metabolic syndrome ,colorectal neoplasms ,preoperative period ,postoperative period ,biomarkers ,Biology (General) ,QH301-705.5 - Abstract
The pathological mechanisms that link the metabolic syndrome (MS) and colorectal cancer (CRC) are most probably related to abdominal obesity and insulin resistance. This study aimed to assess the relationship between MS and its clinical characteristics, with CRC. We investigated the changes in the appearance of MS features three months after surgical treatment, and its relationship with the concentration of tumor and inflammation markers. The retrospective cohort study was performed on 193 patients who were diagnosed with CRC and consequently surgically treated (at the Department of General Surgery, Clinical Hospital Center “Bežanijska kosa”, Belgrade). The included patients were divided into two groups based on the presence of MS. Body mass index (BMI), waist circumference, blood pressure, blood glucose, triglycerides (TG), high density lipoproteins - cholesterol (HDL-C), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA 19-90) and C-reactive protein (CRP) were analyzed at the time when the CRC diagnosis was made and three months after surgery. We observed a significant decrease in the number of patients with MS three months postoperatively compared to the number of patients in the preoperative period (106 versus 81; p
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- 2017
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11. The determinants of initial bleeding and rebleeding of duodenal peptic ulcers
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Lazić Bratislav, Matejić Slaviša, Nikolić Simon, Gačić Jasna, Gačić Dragan, Jovanović Petar, and Odalović Božidar
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duodenum ,ulcer ,hemorrhage ,Medicine - Abstract
Acute bleeding of the upper gastrointestinal tract is an urgent condition with high morbidity, and a significant mortality despite advanced diagnostics and therapy. The goal is to investigate the determinants of the severity of duodenal peptic ulcer bleeding. The research included 304 patients hospitalized for acute bleeding from the upper part of gastrointestinal tract in a five year period. They had been treated in the Clinical Hospital Center Bežanijska Kosa in Belgrade. The diagnosis was made via gastroduodenoscopy. Out of the 304 patients, 197 (65%) suffered from bleeding peptic ulcer. 144 (73,1%) patients suffered from bleeding duodenal ulcer, most frequently with bulbar localization 124/86 (12%); 78 (62,9%) with a duodenal bulb back wall lesion. 48 (35,1%) of the bleeding duodenal ulcers were in the Forrest Ib stage, in 68 (47,2%) patients the size of the ulcer lesion was between 1,1-2,0 cm. A statistically positive correlation was determined between the duodenal ulcer lesions and the intensity of the bleeding (p
- Published
- 2017
12. Religiousness level and citizen preparedness for natural disasters
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Cvetković Vladimir M., Babić Slađana, and Gačić Jasmina
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security ,natural disasters ,citizens ,religiosity level ,perception ,Military Science - Abstract
The subject of quantitative research was examination of relationship between the level of religiousness and perception of citizen's flood disaster preparedness. The aim of such research was a scientific explanation of relationships of these characteristics and the perception. Bearing in mind all local communities in Serbia, where floods occurred or there is a high risk of flooding, the sample including 19 of 150 municipalities and 23 towns was randomly selected, as well as the city of Belgrade, where 2,500 persons were surveyed in 2015. The research included the following communities: Obrenovac, Šabac, Kruševac, Kragujevac, Sremska Mitrovica, Priboj, Batočina, Svilajnac, Lapovo, Paraćin, Smederevska Palanka, Jaša Tomić, Loznica, Bajina Bašta, Smederevo, Novi Sad, Kraljevo, Rekovac and Užice. The research of selected communities was undertaken in the areas which were most affected in relation to the amount of water or potential risk of flooding. The survey used strategy of testing in households with the use of a multistage random sample. The parts in the administrative headquarters, which were threatened by hundred-year-old water or a potential risk of high water were determined in the first stage. In the second stage streets and their parts were established, and in the third stage the households in which the survey was conducted were determined. The number of households was coordinated with the size of the community. The fourth stage of sampling referred to the procedure of respondent selection within previously defined household. The respondent selection was conducted using a random sampling method on the adult household members, who were present at the time of the survey. The results indicate that there is a statistically significant correlation level of religiosity with perception in terms of citizens' preparedness to respond. The research results can contribute to the improvement of citizens' preparedness to respond to such events and can be used to develop the strategy for enhancement of the level of citizens' preparedness to respond.
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- 2017
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13. Geospatial and temporal distribution of forest fires as natural disasters
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Cvetković Vladimir M., Gačić Jasmina, and Jakovljević Vladimir
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security ,emergency situations ,natural disasters ,forest fires ,statistical analysis ,Military Science - Abstract
Forest fires are one of the most significant threats to modern civilization, the study of which requires complex, comprehensive and multidisciplinary approach. The consequences of forest fires are often devastating to lives, health and property of people, but also to the security of the country and the entire international community. In this regard, in order to more effectively protect and prevent serious disruption of functioning of the society or great human, material and environmental losses which exceed the ability of the affected society to cope with the situation, i.e the natural disaster, it is necessary to comprehensively investigate the mentioned natural phenomenon. This paper explains and describes the form, consequences, and temporal and geospatial distribution of forest fires. Using an international database on natural disasters of the Center for Research on the Epidemiology of Disasters (CRED), based in Brussels, with the support of the software package used for statistical analysis (SPSS) and the method of thematic cartography, the authors tried to point to the number, trends, consequences, geospatial and temporal distribution of forest fires in the period from 1900 to 2013, as well as to the need for adequate response of the society to this type of natural disaster.
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- 2016
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14. Climate change and national defense
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Cvetković Vladimir M., Vučić Sandra Z., and Gačić Jasmina
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climate change ,defense ,conflicts ,emergencies ,security ,Military Science - Abstract
Climate change, as one of the greatest challenges facing the contemporary society, continues to attract the attention of both political and scientific community for a rather long time. The variability of climate change consequences, as well as their effects on the environment and humanity, are on the agenda of most international conferences, and discussions on possible strategies for reducing their impact have been held both at national and international levels. However, most of these discussions are restricted mainly to the effects of climate change caused in the environment and, in this framework, to the effects that such changes might have on people's lives in terms of availability of basic supplies and resources. It had been rather long before the consideration of the impact of climate change exceeded the scope of environmental study, and in recent years the awareness of the impacts of climate change on the organization and functioning of national defense, especially in developed countries, has significantly increased. The changed nature of threats poses high standards before systems of defense in terms of capacities and capabilities for providing an effective response. The fact that climate change is affecting different segments of human civilization, which ultimately has an impact on the fulfillment of the mission of defense, necessarily imposes the need to put more efforts in addressing this issue in the future. Therefore, this paper aims, by considering some of the dominant climate change tendencies, to explore their impact on the functioning of the defense in the changing environmental conditions.
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- 2015
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15. Impact of climate change on the distribution of extreme temperatures as natural disasters
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Cvetković Vladimir M., Gačić Jasmina, and Jakovljević Vladimir
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security ,emergency situations ,climate change ,extreme temperatures ,adaptation ,disaster ,distribution ,Military Science - Abstract
Much of the scientific community agrees that global temperature as a result of climate change has increased significantly in the last century, and will continue to grow in the near future. According to the Third Assessment Report of the IPCC, 2001 (IPCC - Intergovernmental Panel on Climate Change), the global average temperature has increased by about 0.6 degrees in the 20th century, although climate warming was not uniform neither spatially nor temporally, as was indicated by observed changes and modelling studies. Variations in global or regional cases of extreme air temperatures that occurred due to changes in climate cause more and more attention lately as living beings and ecosystems and human society are sensitive to the severity, frequency and persistence of cases of extreme temperatures. In this regard, in order to effectively protect and respond to emergencies caused by harmful temperature extremes, it is necessary among other things to comprehensively investigate the mentioned natural phenomenon, so the subject of this paper will be an analysis of climate change as well as form, consequences, temporal and geospatial distribution of extreme temperatures. Using an international database on natural disasters of the Centre for Research on the Epidemiology of Disasters (CRED), based in Brussels, with the support of program for statistical analysis (SPSS) and the method of thematic cartography, we have tried to point out the number, trends, consequences, temporal and geospatial distribution of extreme temperature in the period from 1900 to 2013, as well as the need for an adequate response of society to this type of natural hazard.
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- 2015
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16. Possibilities of the Republic of Serbia for reducing vulnerability to natural hazards
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Gačić Jasmina, Bošković Milica, and Raković Jelena
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vulnerability ,natural hazards ,possibilities ,SCN model ,Geography (General) ,G1-922 - Abstract
Vulnerability is an essential feature of an element at risk (community, region, country, the environment) which determines the expected damage caused by a hazard. Vulnerability modified over time and it depended on physical, social, economic and environmental factors. Vulnerability became multidimensional, multidisciplinary, multi-sectoral and dynamic in contemporary circumstances. In the past decades, vulnerability to natural hazards took precedence over technological and other hazards threatening the community. The necessity to assess threat, vulnerability and the prevention of natural hazards was emphasized in the key national normative legal acts of the Republic of Serbia. A resolute commitment of the country to lay down the laws to regulate this field and establish a system to make a functional response to natural hazards through institutions was followed by difficult circumstances in practice. In addition to permanent flood hazard vulnerability, landslide and earthquake vulnerability, weak socio-economic profile i.e. the insufficient flexibility of the community and the unclear role of government bodies, municipal civil protection service and the service for protection from natural disasters were also insufficiently equipped. Nowadays, government efforts to solve problems in order to improve its own possibilities for reducing vulnerability to natural hazards are evident. The most important are those related to proper financing of the protection system. The application of SCN model would provide a more stable transfer of financial resources, as well as the transfer of necessary manpower and material resources from national to local level.
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- 2013
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17. Lesion of the femoral nerve caused by a hydatid cyst of the right psoas muscle
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Bilanović Dragoljub, Zdravković Darko, Ranđelović Tomislav, Tosković Borislav, and Gačić Jasna
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hydatidosis ,femoral nerve ,paresis ,Medicine - Abstract
Introduction. Hydatidosis is a human disease caused by the larval form of Echinococcus granulosus. All organs in the human body may be affected by hydatid disease, but excluding liver and lungs, all other organs are considered as uncommon locations. Hydatid disease located in the psoas muscle is uncommon. Case Outline. The authors present a 36-year-old male living in endemic areas of Serbia, admitted due to pain and weakness of the right thigh and weight loss. Duration of symptoms was one year. CT and MRI revealed a big cystic mass (20 cm long) in the right psoas muscle. Neurological investigation showed a loss of function of the right femoral nerve. Serology for Echinococcosis was negative. Surgery was indicated and performed by median laparotomy. Total excision of the cyst was done. Pathohystology confirmed the nature of the cyst. Three years after operation the patient was without any signs of disease relapse. Conclusion. Echinococcal disease of the psoas has been very rarely reported, sometimes associated with paraspinal disease and often with vertebral involvement. Cystic or complex retroperitoneal tumour, pyogenic abscess of the psoas and even tuberculosis should be considered in the differential diagnosis. Treatment of choice is surgery. The greatest danger for the patient is dissemination and anaphylactic reaction. Also, compression of adjacent organs may produce significant morbidity.
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- 2010
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18. Multifocal Abrikossoff's granular cell tumor of the oesophagus: Case report
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Ranđelović Tomislav D., Stojšić Zorica M., Gačić Jasna M., Babić Darko N., Stojiljković Miodrag T., Baralić Ivanka M., Granić Miroslav K., Ivanović Nebojša S., and Gačić Dragan M.
- Subjects
multifocal granular cell tumor ,oesophagus ,oesophagectomy ,Medicine - Abstract
INTRODUCTION Granular cell tumors, relatively uncommon soft tissue tumors, have been a matter of debate among pathologists regarding histogenesis for a long time. Less common locations are in the aerodigestive tract including the oesophagus. CASE OUTLINE We have recently treated a rare case, a 37-year old male, who was admitted due to dysphagia and a painful swallow with occasional pharyngo-nasal regurgitation followed with a mild loss of weight. Standard clinical examination including X-ray chest, ECG and laboratory tests did not show pathological findings. Barium contrast oesophagography demonstrated multiple ovoid defects in the wall of the oesophagus. CT scan of the chest confirmed luminal narrowing owing to the tumor of the upper oesophagus. Upper endoscopy showed unusual multifocal nodular lesions alongside the oesophageal axis covered by smooth mucosa. A primary biopsy specimen taken from the largest nodules confirmed an unusual pathological finding of the granular cell tumor. Subtotal, transpleural oesophagectomy was performed and reconstruction was derived by long colon segment interposition through the posterior mediastinum. The postoperative course was uneventful. The operative specimen consisted of four ovoid tumors alongside the oesophagus (the greatest diameter 0.5-1.8, average 1.25). All verified tumors histologicaly consisted of a spindle-shaped or polygonal cells containing small and large eosinophilic granules and central nuclei. Most tumor cells showed strongly positive immunohistochemical staining for S-100 protein. These tumor cells were partially positive for p-53 and Ki-67. No lymph node metastases were detected histologically. CONCLUSION Multifocal granular cell tumor of the oesophagus is an unusual finding with low incidence, and rarely caused symptoms. Pathological features and multiplicity of such tumors emphasized malignant predisposition requiring surgical resection of the oesophagus.
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- 2008
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19. Effects of roads and railways on large game in the belgrade area: A case-study of nine municipalities
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Gacic, D. P., Danilovic, M., Gacic, J., and Dušan Stojnić
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traffic ,chemical accident ,Belgrade ,hunting ground ,roe deer - Abstract
The effects of roads and railways on major species of large game (roe deer and wild boar) have been studied in eight hunting grounds in the Belgrade area (nine municipalities), as well as the consequences of chemical accidents in transport of hazardous materials. Road accidents involving birds, game and other animals (WVC - wildlife vehicle collisions) during 2009-2013 in the Belgrade area result in 10 cases (4.8%) in injuries for drivers and passengers. In total, 267 roe deer and 8 wild boar were killed in traffic by cars and trains. Traffic accidents with roe deer have their maximum in April-May and then in December. The adult sex ratio in roe deer killed in traffic by cars and trains was 2.1 (173 female and 80 male), indicating that females were more vulnerable than males. The yearly traffic kill of roe deer represented between 0.8% and 1.1% of the spring population size. In the Belgrade area, the mobile eco-toxicological laboratory of the City Institute of Public Health Belgrade during 2004-2012 registered 177 chemical accidents (mean = 19.7, range = 13 to 26). The chemical accidents in transport of hazardous materials were sporadic and their consequences were small-scale contamination of the environment and economic losses. At the main transport routes of hazardous materials passing through hunting grounds in the Belgrade area occurred 26 chemical accidents, out of which 11 on the railways and 9 on the roads, and the remainder in air and river transportation (4 and 2, respectively).
20. Penile Skin as a Rare Location of Melanoma in the Balkan Region: A Case Report.
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Gacic J, Lazarov A, Lazarov Bandic M, Bandic J, Nikolovski S, and Nikolic M
- Abstract
Skin melanoma is very rarely found in the genital region. Additionally, out of all penile skin malignancies, melanoma is one of the rarest, with no cases reported before in the Balkan region. A 68-year-old male presented with atypical and irregular pigmented skin lesions on his left flank and penile shaft. After dermoscopy and radiological work-up, both lesions were completely excised, with pathological examination revealing a high-grade dysplastic nevus with nodular melanoma in the penile location. Wide re-excision was performed one month later, followed by skin reconstruction with a rotation cutaneous flap. No postoperative complications, long-term recurrence signs, nor local or distant metastases were observed. As a very rare case of this kind of condition in the Balkan region and globally, this is the first case of penile skin melanoma described in Serbia, additionally emphasizing the importance of thorough systematic clinical examination and conducting organ-preserving surgery.
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- 2025
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21. Trans-visceral Migration of Retained Gauze: A Rare Cause of Intestinal Obstruction.
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Todorovic S, Tesic N, Lukic F, Gacic J, and Toskovic B
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- 2025
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22. Acquired von Willebrand syndrome and post-operative drainage: a comparison of patients with aortic stenosis versus coronary artery disease.
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Djordjevic A, Jovicic V, Lazovic D, Terzic D, Gacic J, Petrovic M, Matejic A, Salovic B, Radovic I, Jesic-Petrovic T, Ristic A, and Soldatovic I
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Drainage, Biomarkers blood, Treatment Outcome, Time Factors, Serbia epidemiology, Aged, 80 and over, Aortic Valve Stenosis surgery, Aortic Valve Stenosis complications, von Willebrand Diseases blood, von Willebrand Diseases complications, von Willebrand Diseases epidemiology, Coronary Artery Disease surgery, Coronary Artery Disease complications, von Willebrand Factor analysis, von Willebrand Factor metabolism, Factor VIII analysis, Factor VIII metabolism, Coronary Artery Bypass adverse effects
- Abstract
Objective: Degenerative aortic stenosis and coronary artery disease are considered to be the most prevalent cardiovascular diseases in industrialized countries. This study aims to determine the change over time in von Willebrand factor antigen, von Willebrand factor activity, and factor VIII and where there is a correlation with total post-operative drainage., Methods: The single-center retrospective study included 203 consecutive patients (64.5% male), undergoing coronary artery bypass surgery between March 1, 2019 and June 30, 2020 at the University Clinical Center of Serbia in the Clinic for Cardiac Surgery in Belgrade, Serbia. All patients 18 years or older who presented with isolated, hemodynamically significant aortic stenosis were included. The control group consisted of patients who presented with only coronary artery disease., Results: Between patients with only coronary artery disease and patients with coronary artery diseases and aortic stenosis, there was a statistically significant difference between pre-op and 1-month post-op fibrinogen, factor VIII, von Willebrand factor antigen, and von Willebrand factor (p < 0.001), post-op drainage, with overall lower drainage in coronary artery disease patients, and consistent increase in von Willebrand factor antigen, von Willebrand factor activity, and Factor VIII post-operatively in patients with coronary artery diseases and aortic stenosis., Conclusion: This study has shown that there is a correlation between von Willebrand factor antigen, von Willebrand factor activity and total drainage to the level of statistical significance in aortic stenosis patients and in the overall study population., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)
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- 2024
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23. The Perioperative Pain Management Bundle is Feasible: Findings From the PAIN OUT Registry.
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Stamenkovic D, Baumbach P, Radovanovic D, Novovic M, Ladjevic N, Dubljanin Raspopovic E, Palibrk I, Unic-Stojanovic D, Jukic A, Jankovic R, Bojic S, Gacic J, Stamer UM, Meissner W, and Zaslansky R
- Subjects
- Humans, Pain, Acetaminophen, Registries, Pain Management, Analgesics, Non-Narcotic
- Abstract
Objectives: The quality of postoperative pain management is often poor. A "bundle," a small set of evidence-based interventions, is associated with improved outcomes in different settings. We assessed whether staff caring for surgical patients could implement a "Perioperative Pain Management Bundle" and whether this would be associated with improved multidimensional pain-related patient-reported outcomes (PROs)., Methods: "PAIN OUT," a perioperative pain registry, offers tools for auditing pain-related PROs and obtaining information about perioperative pain management during the first 24 hours after surgery. Staff from 10 hospitals in Serbia used this methodology to collect data at baseline. They then implemented the "Perioperative Pain Management Bundle" into the clinical routine and collected another round of data. The bundle consists of 4 treatment elements: (1) a full daily dose of 1 to 2 nonopioid analgesics (eg, paracetamol and/or nonsteroidal anti-inflammatory drugs), (2) at least 1 type of local/regional anesthesia, (3) pain assessment by staff, and (4) offering patients information about pain management. The primary endpoint was a multidimensional pain composite score (PCS), evaluating pain intensity, interference, and side effects that was compared between patients who received the full bundle versus not., Results: Implementation of the complete bundle was associated with a significant reduction in the PCS ( P < 0.001, small-medium effect size [ES]). When each treatment element was evaluated independently, nonopioid analgesics were associated with a higher PCS (ie, poorer outcome, and negligible ES), and the other elements were associated with a lower PCS (all negligible small ES). Individual PROs were consistently better in patients receiving the full bundle compared with 0 to 3 elements. The PCS was not associated with the surgical discipline., Discussion: We report findings from using a bundle approach for perioperative pain management in patients undergoing mixed surgical procedures. Future work will seek strategies to improve the effect., Competing Interests: This work was supported by (1) PAIN OUT was developed with funding from the European Community’s Seventh Framework Program FP7/2007-2013, Brussels, Belgium under Grant Agreement No. 223590. (2) The European Pain Federation (EFIC), Brussels, Belgium provided funding to the Serbian Pain Society to cover the costs of the project in Serbia. Funding included: (1) the annual subscription to PAIN OUT for 10 hospitals over a 2-year period, (2) two half-day face-to-face meetings so that the principal investigator and one research surveyor from each participating hospital could review the findings collected, and (3) partial remuneration to hospitals for data sets collected. The funds were transferred to the Serbian Pain Association, which then contacted each of the participating hospitals. W.M. received grants (paid to the institution) and personal fees from Grünenthal, grants (paid to the institution) from Pfizer and Mundipharma. Personal fees from TAD, BioQPharm, Bionorica, Kyowa, Northern Swan, and Tilray. U.M.S. received fees (paid to the institution) and reimbursement for travel costs from Sintetica and Sanofi-Aventis Swiss. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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24. Cytogenetically visible inversions are formed by multiple molecular mechanisms.
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Pettersson M, Grochowski CM, Wincent J, Eisfeldt J, Breman AM, Cheung SW, Krepischi ACV, Rosenberg C, Lupski JR, Ottosson J, Lovmar L, Gacic J, Lundberg ES, Nilsson D, Carvalho CMB, and Lindstrand A
- Subjects
- Comparative Genomic Hybridization, Female, Gene Frequency, Haplotypes, Heterozygote, Homologous Recombination, Humans, Karyotyping, Male, Pedigree, Whole Genome Sequencing, Chromosome Inversion, DNA End-Joining Repair, DNA Repair
- Abstract
Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients., (© 2020 The Authors. Human Mutation published by Wiley Periodicals LLC.)
- Published
- 2020
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25. Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization.
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Nazaryan-Petersen L, Eisfeldt J, Pettersson M, Lundin J, Nilsson D, Wincent J, Lieden A, Lovmar L, Ottosson J, Gacic J, Mäkitie O, Nordgren A, Vezzi F, Wirta V, Käller M, Hjortshøj TD, Jespersgaard C, Houssari R, Pignata L, Bak M, Tommerup N, Lundberg ES, Tümer Z, and Lindstrand A
- Subjects
- Alu Elements, Chromosome Breakpoints, Chromothripsis, Gene Rearrangement, Genome, Human, Humans, Long Interspersed Nucleotide Elements, Oligonucleotide Array Sequence Analysis, Whole Genome Sequencing, DNA Copy Number Variations, DNA Replication genetics
- Abstract
Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both "simple" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements., Competing Interests: The authors have declared that no competing interests exist.
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- 2018
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26. Intraoperative ultrasound in breast cancer surgery-from localization of non-palpable tumors to objectively measurable excision.
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Colakovic N, Zdravkovic D, Skuric Z, Mrda D, Gacic J, and Ivanovic N
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- Biopsy, Breast pathology, Breast surgery, Breast Neoplasms pathology, Breast Neoplasms surgery, Female, Humans, Intraoperative Care, Mastectomy, Mastectomy, Segmental, Prognosis, Breast diagnostic imaging, Breast Neoplasms diagnostic imaging, Margins of Excision, Ultrasonography, Mammary methods
- Abstract
Background: The utilization of intraoperative ultrasound (IOUS) in breast cancer surgery is a relatively new concept in surgical oncology. Over the last few decades, the field of breast cancer surgery has been striving for a more rational approach, directing its efforts towards removing the tumor entirely yet sparing tissue and structures not infiltrated by tumor cells. Further progress in objectivity and optimization of breast cancer excision is possible if we make the tumor and surrounding tissue visible and measurable in real time, during the course of the operation; IOUS seems to be the optimal solution to this complex requirement. IOUS was introduced into clinical practice as a device for visualization of non-palpable tumors, and compared to wire-guided localization (WGL), IOUS was always at least a viable, or much better alternative, in terms of both precision in identification and resection and for patients' and surgeons' comfort. In recent years, intraoperative ultrasound has been used in the surgery of palpable tumors to optimize resection procedures and overcome the disadvantages of classic palpation guided surgery., Objective: The aim of this review is to show the role of IOUS in contemporary breast cancer surgery and its changes over time., Methods: A PubMed database comprehensive search was conducted to identify all relevant articles according to assigned key words., Conclusion: Over time, the use of IOUS has been transformed from being the means of localizing non-palpable lesions to an instrument yielding a reduced number of positive resection margins, with a smaller volume of healthy breast tissue excided around tumor, by making the excision of the tumor optimal and objectively measurable.
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- 2018
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27. Homocysteine is the confounding factor of metabolic syndrome-confirmed by siMS score.
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Srećković B, Soldatovic I, Colak E, Mrdovic I, Sumarac-Dumanovic M, Janeski H, Janeski N, Gacic J, and Dimitrijevic-Sreckovic V
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- Adult, Age Factors, Aged, Biomarkers blood, Blood Glucose analysis, C-Reactive Protein analysis, Confounding Factors, Epidemiologic, Cross-Sectional Studies, Decision Support Techniques, Dyslipidemias blood, Dyslipidemias diagnosis, Female, Fibrinogen analysis, Humans, Hyperhomocysteinemia diagnosis, Inflammation Mediators blood, Insulin Resistance, Lipids blood, Male, Metabolic Syndrome diagnosis, Metabolic Syndrome physiopathology, Middle Aged, Obesity, Abdominal blood, Obesity, Abdominal diagnosis, Obesity, Abdominal physiopathology, Predictive Value of Tests, Risk Factors, Up-Regulation, Uric Acid blood, Homocysteine blood, Hyperhomocysteinemia blood, Metabolic Syndrome blood
- Abstract
Background: Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflammatory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteinemia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hypertension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors., Methods: The study included 69 obese individuals (age over 30, body mass index [BMI] >25 kg/m2), classified into two groups: I-with MS (33 patients); II-without MS (36 patients). Measurements included: anthropometric parameters, lipids, glucose regulation parameters and inflammation parameters. IR was determined by homeostatic model assessment for insulin resistance (HOMA-IR). ATP III classification was applied for diagnosing MS. SiMS score was used as continuous measure of metabolic syndrome., Results: A significant difference between groups was found for C-reactive protein (CRP) (p<0.01) apolipoprotein (Apo) B, HOMA-IR and acidum uricum (p<0.05). siMS risk score showed a positive correlation with homocysteine (p=0.023), while siMS score correlated positively with fibrinogen (p=0.013), CRP and acidum uricum (p=0.000) and homocysteine (p=0.08). Homocysteine correlated positively with ApoB (p=0.036), HbA1c (p=0.047), HOMA-IR (p=0.008) and negatively with ApoE (p=0.042)., Conclusions: Correlation of siMS score with homocysteine, fibrinogen, CRP and acidum uricum indicates that they are co-founding factors of MS. siMS risk score correlation with homocysteine indicates that hyperhomocysteinemia increases with age. Hyperhomocysteinemia is linked with genetic factors and family nutritional scheme, increasing the risk for atherosclerosis.
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- 2018
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28. Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery.
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Bojic S, Kotur-Stevuljevic J, Aleksic A, Gacic J, Memon L, and Simic-Ogrizovic S
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- Aged, Biomarkers blood, Biomarkers urine, Case-Control Studies, Female, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Respiration, Artificial, Sepsis blood, Sepsis etiology, Sepsis urine, Severity of Illness Index, Survival Analysis, Abdomen surgery, Matrix Metalloproteinase 9 blood, Matrix Metalloproteinase 9 urine, Sepsis metabolism, Tissue Inhibitor of Metalloproteinase-1 blood, Tissue Inhibitor of Metalloproteinase-1 urine
- Abstract
Background: The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored., Materials and Methods: Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded., Results: Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels., Conclusions: MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction.
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- 2018
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29. Homocysteine is a marker for metabolic syndrome and atherosclerosis.
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Sreckovic B, Sreckovic VD, Soldatovic I, Colak E, Sumarac-Dumanovic M, Janeski H, Janeski N, Gacic J, and Mrdovic I
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- Adult, Aged, Albuminuria blood, Albuminuria diagnosis, Albuminuria epidemiology, Atherosclerosis epidemiology, Biomarkers blood, Blood Glucose metabolism, Cross-Sectional Studies, Female, Humans, Male, Metabolic Syndrome epidemiology, Middle Aged, Obesity blood, Obesity diagnosis, Obesity epidemiology, Waist Circumference physiology, Atherosclerosis blood, Atherosclerosis diagnosis, Homocysteine blood, Metabolic Syndrome blood, Metabolic Syndrome diagnosis
- Abstract
Background: It has been documented that patients with metabolic syndrome (MS) and vascular complications have higher homocysteine levels. Hyperhomocysteinemia correlates with IR, increasing oxidative stress, which causes lesions of vascular endothelium leading to endothelial dysfunction, hypertension and atherosclerosis., Objective: The objectives of the study were to examine homocysteine values, along with cardiovascular risk factors (lipid and apolipoprotein status, CRP, blood pressure), indicators of renal function (microalbuminuria/24h), glucose regulation and insulin resistance (glucose and insulin level, HbA1c, HOMA-IR, uric acid) and anthropometric parameters (BMI, WC, HC, WHR) in patients with and without MS as a correlation between homocysteine and MS factors., Methods: The study included obese and overweight individuals, aged of 30-75 yrs. classified into two groups: with MS (n=35) and without MS (n=41)., Results: Patients with MS had increased WC, BMI, BP, glycaemia, HOMA-IR, TG, CRP, microalbuminuria, homocysteine and decreased HDL-C (p<0.05). Statistically significant difference between groups was found for WC, BMI, sBP and dBP, TG, HDL-C (p<0.01) and glycaemia, CRP, Apo B, HOMA-IR (p<0.05). Significant positive correlations were found between homocysteine and sBP (p=0.036), dBP (p=0.04), Apo B (p=0.038) and hyperlipoproteinemia (type IIa, type IIb and type IV) (p=0.04)., Conclusion: Patients with MS had increased abdominal obesity, hypertension, hypertriglyceridemia, inflammation factors, IR, homocysteine and microalbuminuria as markers of endothelial dysfunction. A correlation between homocysteine and hypertension and hyperlipoproteinemia showed that homocysteine could be used as a potential marker for atherosclerosis progression., (Copyright © 2016. Published by Elsevier Ltd.)
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- 2017
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30. Benign Hydronephrosis and Elevated of Serum Levels of Carbohydrate Antigen CA 19-9: A Case Report.
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Filipovic B, Milinić N, Gacic J, Markovic O, Djokovic A, and Filipovic B
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- Biomarkers blood, Humans, Male, Middle Aged, Antigens, Tumor-Associated, Carbohydrate blood, Hydronephrosis etiology, Urolithiasis diagnosis
- Abstract
Background: Carbohydrate tumor-associated antigen (CA 19-9) has been shown to be upregulated in other malignant tumors including gastric, ovarian, hepatocellular, and colorectal carcinoma as well as benign diseases of the biliary track such as pancreatitis, cholangitis, and choledocholithiasis. According to the available literature, in several cases of benign hydronephrosis and in a few cases of benign renal diseases, elevated CA 19-9 has been noted., Case Report: A 58-year-old Caucasian male patient was admitted in our clinic with complaints about blunt abdominal pain in the past two-month period localized in the right lumbar region and irradiating into the right inguinal area, constipation, abdominal bloating, and intermittent hematuria. The concentration of serum CA 19-9 was 3500 U/mL. Urine cytology provided no signs of abnormality. Intravenous urography visualized right-sided pyelon and ureter duplex with the defect in contrast shade of the pyelon, caused by a stag horn calculus. Contrast added computerized axial tomography of the abdomen and pelvis visualized the pyelon casted concretion spreading throughout the right pyelon, with ureterohydronephrosis with the distal block for passage of the contrast to the distal part of the ureter., Conclusions: There is no doubt that CA 19-9 level is occasionally elevated in patients with obstructive urolithiasis as it was in our case. In the routine medical praxis, urolithiasis should not be neglected in the differential diagnosis of elevated concentrations of CA 19-9 marker.
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- 2016
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31. Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer.
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Hilborn E, Gacic J, Fornander T, Nordenskjöld B, Stål O, and Jansson A
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- Aged, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Female, Follow-Up Studies, Humans, Immunohistochemistry, Middle Aged, Neoplasm Grading, Prognosis, Proportional Hazards Models, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology, Tumor Burden, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms metabolism, Estrogen Receptor alpha metabolism, Neoplasm Recurrence, Local, Receptor, ErbB-2 metabolism, Receptors, Androgen metabolism, Receptors, Progesterone metabolism, Tamoxifen therapeutic use
- Abstract
Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation., Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer., Methods: Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point., Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR)=0.34; 95% confidence interval (CI)=0.14-0.81; P=0.015), whereas the opposite was seen in the AR- group (HR=2.92; 95% CI=1.16-7.31; P=0.022). Interaction test was significant P<0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR=0.12; 95% CI=0.014-0.95 P=0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR=3.98; 95% CI=1.32-12.03; P=0.014). Interaction test was significant P=0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression., Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.
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- 2016
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32. Imatinib reduces cholesterol uptake and matrix metalloproteinase activity in human THP-1 macrophages.
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Gacic J, Vorkapic E, Olsen RS, Söderberg D, Gustafsson T, Geffers R, Skoglund K, Matussek A, and Wågsäter D
- Subjects
- Cells, Cultured, Enzyme Activation drug effects, Enzyme Activation physiology, Humans, Macrophages drug effects, Cholesterol metabolism, Imatinib Mesylate pharmacology, Macrophages metabolism, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Protein Kinase Inhibitors pharmacology
- Abstract
Background: Imatinib mesylate (Glivec®, formerly STI-571) is a selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. However, there are reports suggesting that imatinib could be atheroprotective by lowering plasma low-density lipoprotein (LDL)., Aim: To investigate the potential inhibitory effect of imatinib on cholesterol uptake in human macrophages as well as its effect on matrix metalloproteinase (MMP) activity., Methods and Results: Uptake of fluorescence-labeled LDL was analyzed using flow cytometry. Macrophages treated with imatinib showed a 23.5%, 27%, and 15% decrease in uptake of native LDL (p<0.05), acetylated LDL (p<0.01), and copper-modified oxidized LDL (p<0.01), respectively. Gel-based zymography showed that secretion and activity of MMP-2 and MMP-9 were inhibited by imatinib. Using GeneChip Whole Transcript Expression array analysis, no obvious gene candidates involved in the mechanisms of cholesterol metabolism or MMP regulation were found to be affected by imatinib. Instead, we found that imatinib up-regulated microRNA 155 (miR155) by 43.8% and down-regulated ADAM metallopeptidase domain 28 (ADAM28) by 41.4%. Both genes could potentially play an atheroprotective role and would be interesting targets in future studies., Conclusion: Our results indicate that imatinib causes post-translational inhibition with respect to cholesterol uptake and regulation of MMP-2 and MMP-9. More research is needed to further evaluate the role of imatinib in the regulation of other genes and processes., (Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)
- Published
- 2016
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