Abstract Prolyl hydroxylases catalyze the post-translational formation of 3- and 4-hydroxyprolines in polypeptides. To date, two prolyl 4-hydroxylase families are known to exist: collagen prolyl 4-hydroxylases (C-P4Hs) which reside in the endoplasmic reticulum, and hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) which reside in either the cytoplasm or nucleus. C-P4Hs and HIF-P4Hs belong to the 2-oxoglutarate dioxygenase family and require Fe2+, 2-oxoglutarate, O2 and ascorbate in their reaction. C-P4Hs are critical enzymes in collagen biosynthesis since the formation of 4-hydroxyproline residues stabilizes the collagen triple helix at body temperature. HIF-P4Hs regulate, through hypoxia-inducible factor HIF, the expression of genes that are essential for the survival of cells during hypoxia. This thesis reports the cloning and characterization of two novel P4Hs, from human and a plant, which show some distinct features when compared to previously characterized P4Hs. The human P4H was found to have a unique transmembrane domain, with its catalytic region residing inside the lumen of the endoplasmic reticulum, its subcellular localization thus being identical to that of the C-P4Hs. However, unlike C-P4Hs, it hydroxylated HIF-α both in vitro and in cellulo. Furthermore, its expression level was induced in hypoxic conditions in most of the cell lines studied. The Arabidopsis thaliana P4H had distinct differences in its substrate specificity when compared to another previously characterized A. thaliana P4H. Interestingly, the putative peptide binding regions of the two new P4Hs characterized in this study shared some homology. Three prolyl 3-hydroxylase (P3H) isoenzymes are known to exist in vertebrates and they also belong to the 2-oxoglutarate dioxygenases. It is known that 3-hydroxyprolines are found only in collagens, being most abundant in type IV collagen. The function of this modification is as yet poorly understood, but its absence in collagen I has recently been shown to lead to recessive lethal osteogenesis imperfecta. The human P3H isoenzymes were cloned during these thesis studies, and were expressed as recombinant proteins. The kinetic properties of one of them, P3H2, which was found to be expressed in structures rich with basement membranes, was studied in detail. / Tiivistelmä Prolyylihydroksylaasit ovat entsyymejä, jotka katalysoivat 3- ja 4-hydroksiproliinien muodostumisen valkuaisaineissa. Nykyisin tunnetaan ainakin kaksi prolyyli-4-hydroksylaasien (P4H) entsyymiperhettä: endoplasmakalvostossa sijaitsevat kollageeni prolyyli-4-hydroksylaasit (kollageeni-P4H:t) sekä vähähappisissa olosuhteissa aktivoituvaa transkriptiotekijää, hypoksiaindusoituvaa faktoria (HIF), hydroksyloivat prolyyli-4-hydroksylaasit (HIF-P4H:t). HIF-P4H:t sijaitsevat sytoplasmassa ja tumassa. Sekä kollageeni-P4H:t että HIF-P4H:t kuuluvat 2-oksoglutaraattidioksygenaasien laajaan entsyymiperheeseen. Nämä entsyymit tarvitsevat kosubstraateikseen rautaa, 2-oksoglutaraattia, happea sekä C-vitamiinia. Kollageeni-P4H:t hydroksyloivat kollageenien proliinitähteitä ja ovat avainasemassa kollageenisynteesissä, sillä muodostuneet 4-hydroksiproliinitähteet ovat ehdoton vaatimus stabiilille kollageenirakenteelle. HIF-P4H:t säätelevät puolestaan niiden geenien ilmenemistä, jotka ovat välttämättömiä elimistön selviytymiselle vähähappisissa olosuhteissa. HIF-P4H:t hydroksyloivat HIF-transkriptiotekijän α-alayksikön tiettyjä proliinitähteitä hapen läsnä ollessa, joka ohjaa α-alayksikön proteasomaaliseen hajotukseen eikä aktiivista HIF transkriptiotekijää siten muodostu. Alentuneessa happipitoisuudessa HIF-P4H entsyymien toiminta estyy, HIF stabiloituu ja aktivoi kohdegeeniensä toiminnan. Kollageeni-P4H entsyymejä pidetään erityisen sopivina lääkekehityksen kohteina fibroottisten ja HIF-P4H entsyymejä iskeemisten sairauksien hoitoon. Tässä väitöskirjatyössä on karakterisoitu aiemmin tuntematon ihmisen transmembraaninen P4H entsyymi (P4H-TM). Entsyymi osoittautui indusoituvan vähähappisissa olosuhteissa useissa solulinjoissa ja hydroksyloivan HIF-transkriptiotekijää muistuttaen siten HIF-P4H entsyymejä. Kuitenkin P4H-TM:n solulokalisaatio poikkesi HIF-P4H entsyymeistä, sillä sen havaittiin sijaitsevan endoplasmakalvostossa, katalyyttinen keskus kalvoston sisällä. Näiden tutkimustulosten valossa on oletettavaa, että tällä ihmisentsyymillä on HIF:n lisäksi toinen toistaiseksi tuntematon fysiologinen substraatti. Väitöskirjassa karakterisoitiin toinen lituruohon, Arabidopsis thalianan, P4H (At-P4H-2), joka poikkesi katalyyttisiltä ominaisuuksiltaan aiemmin karakterisoidusta lituruohon P4H:sta. Näiden kahden kasvientsyymin substraattivaatimusten poiketessa selvästi toisistaan, on niillä solussa todennäköisesti spesifiset tehtävät. At-P4H-2:n oletetulla substraatin sitomisalueella on jakso, joka on 37-prosenttisesti identtinen ihmisen P4H-TM:n kanssa, minkä vuoksi At-P4H-2:n karakterisoinnin uskottiin olevan tärkeä apuväline ihmisen P4H-TM:n tutkimuksissa. Selkärankaisilla prolyyli-3-hydroksylaaseja (P3H) tiedetään olevan kolme, ja myös ne kuuluvat 2-oksoglutaraattidioksygenaaseihin. 3-Hydroksiproliinia esiintyy ainoastaan kollageeneissa, erityisesti tyypin IV kollageenissa, joka on tyvikalvojen tärkeä rakennekomponentti. 3-Hydroksiproliinin merkitystä ei tunneta vielä tarkoin, mutta tyypin I kollageenissa 3-hydroksiproliinin puutoksen on osoitettu johtavan vaikeaan luustosairauteen, osteogenesis imperfectaan. Väitöskirjatyössä ihmisen P3H:t kloonattiin ja tuotettiin rekombinanttiproteiineina. Yhden isoentsyymin (P3H2) katalyyttiset ominaisuudet määritettiin ja sen osoitettiin ilmenevän erityisesti kudoksissa, joissa on paljon tyvikalvorakenteita.

<p>U radu se analiziraju agroekonomski faktori odrţivog razvoja na primeru regiona Fru&scaron;ke gore. Potreba za istraţivanjem ovih faktora polazi od ĉinjenice da je poljoprivreda najzastupljenija delatnost u ovom regionu, taĉnije u njegovoj za&scaron;titnoj zoni. Identifikovanje i kvantifikovanje agroekonomskih faktora putem relevantnih indikatora odrţive poljoprivrede pro&scaron;ireno je i na aspekt ruralnog razvoja. U radu je dat pregled vladajuće literature, kao i veći broj metodologija odrţivog razvoja, odrţive poljoprivrede i ruralnog razvoja. Prikazani su razliĉiti pristupi u regionalne ekonomije i oceni regionalne konkurentnosti ruralnih podruĉja u cilju sveobuhvatne analize posmatrane problematike. Date su karakteristike istraţivanog prostora na primeru Fru&scaron;ke gore (potencijala za odrţivi razvoj, profili op&scaron;tina/gradova koji ulaze u obuhvat ovog regiona, kao i prikaz odrţivih opredeljenja za sve delatnosti). Na osnovu dostupnih podataka analiziran je uticaj pojedinih agroekonomskih faktora odrţivog razvoja regiona Fru&scaron;ke gore, i data je procena njihovog daljeg delovanja u budućem periodu, uz uvaţavanje ostalih ekonomskih pokazatelja Republike Srbije i AP Vojvodine. U dokazivanju ili opovrgavanju hipoteza, osim identifikacije agroekonomskih faktora odrţivog razvoja, kori&scaron;ćeno je anketno istraţivanje svih zainteresovanih subjekata u regionu Fru&scaron;ke gore. Isto tako, izloţene su ideje i predlozi za buduća istraţivanja i predloţen je model koji bi na najoptimalniji naĉin valorizovao sve potencijale Fru&scaron;ke gore, a prvenstveno onih koji su u funkciji unapreĊenja poljoprivrede, ruralnog i odrţivog razvoja.</p> / <p>This paper analyses agrieconomics factors of sustainable development in the case of region of Fru&scaron;ka gora. The need for research on these factors comes from the fact that agriculture is the most common activity in the region, specifically in its protective zone. An identifying and quantifying agrieconomics factor through relevant indicators of sustainable agriculture has been extended to an aspect of rural development. The paper gives an overview of the actual literature, and a number of methodologies for sustainable development, sustainable agriculture and rural development. Different theoretical approaches of the regional economy and the assessment of regional competitiveness of rural areas are presented, in order a comprehensive analysis of the observed issues. The characteristics of the area in the case of Fru&scaron;ka gora are presented (potential for sustainable development, profiles of municipalities/cities which are located in the scope of this region, as well as the sustainable orientation for all business activity). Based on available data, was analysed the influence of the certain agrieconomics factors of sustainable development of the region of Fru&scaron;ka gora, and assessment of their impact in the following period, together with other economic indicators of the Republic of Serbia and AP Vojvodina. In proving or disproving the hypothesis, except the identification agrieconomics factors of sustainable development, the research by a survey questionnaire of all stakeholders in the region of Fru&scaron;ka gora was used. Also, the ideas and suggestions for future research are expressed and a model that would optimally valorised all potentials of Fru&scaron;ka gora is proposed, primarily those that are aimed at improving the agricultural, rural and sustainable development.</p>

<p>Doktorska disertacija odnosi se na analizu najznačajnijih kriterijuma<br />koje posmatraju investitori prilikom ulaganja na tržišta u razvoju.<br />Poređenjem šest evropskih berzanskih indeksa tržišta u razvoju i<br />svetski najznačajnijeg berzanskog indeksa - S&amp;P 500, dobijeni su<br />rezultati koji ukazuju da postoji značajnost u zavisnosti nivoa cena od<br />kretanja na globalnom tržištu, a koja su posledica postojanja<br />internacionalnih investitora. Dobijeni rezultati mogu se koristiti<br />kao osnova za dalja istraživanja u oblasti od strane akademske<br />zajednice, kao i od strane profesionalnih učesnika na finansijskim<br />tržištima, kao pomoć prilikom donošenja njihovih investicionih<br />odluka. Od posebnog interesa je mogućnost primene rezultata u vođenju<br />ekonomske i finansijske politike Republike Srbije.</p> / <p> markets investors. Comparison of six European emerging stock market<br /> indices and world&rsquo;s the most important stock exchange index - the S&amp;P 500,<br /> established a level of emerging markets price dependence on international<br /> investors with global market overview. The results obtained can be used as a<br /> basis for further research in the field by the academic community, as well as<br /> by professional investors in financial markets, to assist in making their<br /> investment decisions. Of particular interest is the possibility of applying the<br /> results in economic and financial decision making policy of the Republic of<br /> Serbia.</p>

<p>Cilj ovog istraživanja je bio da se utvrdi nivo folne kiseline u serumu (fiziolo&scaron;ka vrednost je od 16,31 do 34,88 nmol/l) i proceni težina kliničke slike instrumentima kliničke procene (HAMD 17 i 21, MADRS i CGI skala) u populaciji bolnički lečenih pacijenata, koji boluju od te&scaron;ke depresivne epizode, ili rekurententog depresivnog poremećaja, i njihov odgovor na inicijalnu antidepresivnu terapiju sprovođenu prema smernicama nacionalnog vodiča. Odgovor na antidepresivnu terapiju je određivan nakon četiri i osam nedelja lečenja u odnosu na nivo folne kiseline i prema nadoknadi folne kiseline u dozi od 15 mg dnevno (kod pacijenata koji nisu adekvatno odreagovali na terapiju). Smatrano je da je antidepresivni odgovor adekvatan ukoliko je utvrđena redukcija skora na HAMD (17, 21) i MADRS za 50%. Istraživanje je obuhvatilo 102 pacijenata (69 osoba ženskog pola i 33 osobe mu&scaron;kog pola) starosti između 18 i 70 godina života. Utvrđeno je da je snižen nivo folne kiseline u krvi imalo 41,2% pacijenata.<em> X</em>² testom je ustanovljeno da postoje značajne razlike nivoa folne kiseline u krvi u odnosu na pol. Snižen nivo folne kiseline je zastupljeniji kod osoba mu&scaron;kog pola. Pacijenati sa sniženim nivoom folne kiseline su imali inicijalno značajno vi&scaron;e skorove na skalama kliničke procene i izostanak adekvatnog terapijskog odgovora u četvrtoj nedelji lečenja. U osmoj nedelji lečenja se ta razlika u terapijskom odgovoru izgubila. Utvrđena je statistički značajna razlika u skorovima na HAMD (17) i MADRS u tri merenja u zavisnosti od nivoa folne kiseline i nadoknade uz upotrebu vi&scaron;esmerne me&scaron;ovite analize varijanse (ANOVA). Utvrđeno je da postoji značajan glavni efekat merenja (skorovi se značajno razlikuju od merenja do merenja), i značajan efekat interakcije merenja i nadoknade.</p> / <p>The aim of this paper is to establish the levels of folic acid in serum (physiological values is from 16.31 to 34.88 nmol/l) and the assessment of seriousness of clinical picture by clinical assessment instruments (HAMD 17 and 21, MADRS and CGI scales) in the population of hospitalized patients suffering from severe depressive episodes, or recurrent depressive disorder, and their response to the initial anti-depressant therapy administered according to national guidelines. The response to anti-depressant therapy was determined after four or eight weeks of treatment in relation to the levels of folic acid and according to recuperation of folic acid in the dose of 15 mg daily (in patients who did not react adequately to the therapy). It was believed that the anti-depressive response was satisfying in case of the established score reduction on HAMD (17, 21) and MADRS for 50%. The research encircled 102 patients (69 of whom female patients and 33 males) aged between 18 and 70. A reduced level of folic acid in blood was found in 41.2% of the patients. By<em> X</em>² test determined that there were significant differences in the levels of folic acid in relation to the patient gender. A reduced level was more found in male patients. The patients with reduced levels of folic acid had initially significantly higher scores on clinical assessment scales and the lack of an adequate therapeutic response in the fourth week of the treatment. In the eighth week of the treatment that difference vanished in therapeutic response. A statistically significant difference was determined on HAMD (17) and MADRS during three measurements depending on the levels of folic acid and its recuperation by using a multiway diverse analysis of variance (ANOVA). It was determined that there is a significant central effect of measurements (scores significantly differ from measurement to measurement), as well as an effect of interaction of measurements and the recuperation.</p>

<p>Hronične inflamatorne bolesti disajnih organa su&nbsp;jedan od vodećih uzroka morbiditeta i mortaliteta&nbsp;&scaron;irom sveta. I pored stalnog napretka u naučnim&nbsp;istraživanjima, u otkrivanju molekularnih i ćelijskihmehanizama koji doprinose progresiji bolesti, uvođenju novih prognostičkih biomarkera, novim&nbsp;metodama detektovanja infektivnih uzročnika,&nbsp;primeni novih moćnih bronhodilatatornih,&nbsp;antiniflamatornih i antiinfektivnih lekova, hronične&nbsp;plućne bolesti i danas u dvadeset prvom veku beleže&nbsp;stalan porast broja obolelih i umrlih. Prema savremenom tumačenju HOBP je&nbsp; heterogena bolest koja je udružena sa brojnim komorbiditetima i&nbsp;sistemskim manifestacijama. Zajednički faktori rizika&nbsp;su osnova za javljanje udruženih hroničnih bolesti. Komorbiditeti i akutne egzacerbacije doprinose&nbsp;ukupnoj težini bolesti . S obzirom da se HOBP&nbsp;manifestuje i izvan pluća kod svakog pacijenta je&nbsp;potrebno proceniti postojanje sistemskih&nbsp;manifestacija&nbsp; i tragati za komorbiditetima. U reviziji&nbsp;&bdquo;Globalne strategije za dijagnozu, lečenje i prevenciju hronične opstruktivne bolesti pluća H GOLD&ldquo;&nbsp; iz 2011. godine navedene sledeće pridružene bolesti za&nbsp;kojima je potrebno aktivno tragati: kardiovaskularne&nbsp;bolesti, disfunkcija skeletnih mi&scaron;ića, metabolički&nbsp;sindrom, osteoporoza, depresija i karcinom pluća.&nbsp;Bronhiektazije sepredstavljaju hronično oboljenje&nbsp;pluća koje se karakteri&scaron;e abnormalnim pro&scaron;irenjem&nbsp;lumena bronha koje je uzrokovano slabljenjem ili&nbsp;destrukcijom mi&scaron;ićnih i elastičnih komponenti&nbsp;bronhijalnog zida, smanjenim klirensom mukusa i&nbsp;čestim infekcijama respiratornog trakta. Bronhiektazije se nekim svojim&nbsp; kliničkim&nbsp;karakteristikama preklapaju&nbsp; sa hroničnom opstruktivnom bolesti pluća. Metabolički sindrom&nbsp;predstavlja skup metaboličkih poremećaja koji&nbsp;povećavaju rizik za razvoj kardiovaskularnih bolesti i tipa 2 &scaron;ećerne bolesti. Za na&scaron;e istraživanje smo&nbsp;koristili definiciju NCEPHATPIII prema kojoj se metabolički sindrom zasniva na prisustvu tri od pet&nbsp;komponenti: Abdominalna gojaznost (obim struka&nbsp;preko 102 cm za&nbsp; mu&scaron;karce i preko 88 cm za žene),&nbsp;povi&scaron;ene vrednosti triglicerida na&scaron;te preko 1,7 mmol/l ili od ranije lečen poremećaj, snižen nivo HDL&nbsp;holesterola manje od 1,03 mmol/l za mu&scaron;karce i&nbsp;manje od 1,29 mmol/l za žene ili već lečen&nbsp;poremećaj, povi&scaron;en sistolni krvni pritisak preko 130 mmHg i/ili dijastolni preko 85 mmHg ili već lečena&nbsp;hipertenzija, povi&scaron;en nivo glukoze na&scaron;te preko 5,6 mmol/l ili već postojeći tip 2 &scaron;ećerne bolesti.&nbsp;Istraživenje je sprovedeno u Institutu za plućne&nbsp;bolesti Vojvodine u Sremskoj Kamenici. Cilj je bio&nbsp;da se utvrdi učestalost metaboličkog sindroma i&nbsp;komponenti među bolesnicima sa HOBP i&nbsp;bronhiektazijama. Sledeći cilj je bio da analizira&nbsp;i uporedi&nbsp; zastupljenosti metaboličkog sindroma i pojedinih komponenti među ispitivanim grupama u&nbsp;odnosu na pol, starost bolesnika i dužinu lečenja&nbsp;HOBP. Bilo je uključeno ukupno 193 ispitanika. Od&nbsp;ovog broja 163 su činili bolesnici od HOBP i&nbsp;bronhiektazija&nbsp; koji su bili podeljeni u tri grupe:&nbsp;pacijenti oboleli od hronične opstruktivne bolesti&nbsp;pluća (n=55, grupa 1), pacijenti oboleli od bronhiektazija (n=50, grupa 2) i pacijenti sa&nbsp;udruženom hroničnom opstruktivnom bolesti pluća i&nbsp;bronhiektazijama (n=58, grupa 3). Kontrolna grupa,&nbsp;koja je označena kao grupa 4, formirana je od 30&nbsp;ispitanika bez bronhiektazija i hronične opstruktivne bolesti pluća, tako da je ukupan broj ispitanika u&nbsp;istraživanju bio 193. Učestalost metaboličkog&nbsp;sindroma prema kriterijumuma NCEP/ATP III kod&nbsp;bolesnika hroničnim bolestima respiratornog sistema&nbsp;(hroničnom opstruktivnom bolesti pluća,&nbsp;bronhiektazijama i udružena ova dva oboljenja) je&nbsp;iznosila je kod 37,3 % . Metabolički sindrom je bio&nbsp;učestaliji kod ispitanika sa hroničnim opstruktivnom<br />bolesti pluća i/ili bronhiektazijama u odnosu na&nbsp;ispitanike iz kontrolne grupe bez&nbsp; hroničnih bolesti&nbsp;respiratornog trakta. Kod bolesnika sa hroničnom&nbsp;opstruktivnom bolesti pluća dokazano je prisustvo&nbsp;metaboličkog sindroma kod 38,2%&nbsp; ispitanika, kod&nbsp;bolesnika sa bronhiektazijama kod 54% ispitanika i&nbsp;IV kod pacijenata sa udruženom hroničnom&nbsp;opstruktivnom bolesti pluća i bronhiektazijama kod&nbsp;36,2% ispitanika. Prosečan broj komponenti&nbsp;metaboličkog sindroma kod bolesnika sa hroničnom&nbsp;opstruktivnom bolesti pluća je iznosio 2,18, kod&nbsp;bolesnika sa bronhiektazijama je bio 2,56, a kod&nbsp;bolesnika sa udružena ova dva oboljenja 2,1.<br />Komponente metaboličkog sindroma nisu učestalije i&nbsp;nisu statistički vi&scaron;e kod bolesnika sa udruženom&nbsp;hroničnom opstruktivnom bolesti pluća i&nbsp;bronhiektazijama u odnosu na obolele sa HOBP i&nbsp;bronhiektazijama kao samostalnim oboljenjima.<br />Razlika u pojedinačnim vrednostima komoponenti&nbsp;metaboličkog sindroma i učestalosti pojedinih&nbsp;komponenti među posmatranim grupama bolesnika sa<br />hroničnim plućnim bolestima nije statistički značajna.&nbsp;Učestalost metaboličkog sindroma kod bolesnika sa&nbsp;hroničnim bolestima respiratornog sistema nije u vezi sa polom i ne zavisi od starosti ispitanika. Nije&nbsp;dokazano da je metabolički sindrom učestaliji kod&nbsp;mu&scaron;karaca i i nije dokazano da je učestaliji kod&nbsp;ispitanika koji imaju vi&scaron;e od &scaron;esdeset i pet godina&nbsp;u odnosu na mlađe bolesnike među ispitivanim.&nbsp;Učestalost metaboličkog sindroma kod ispitanika sa&nbsp;hroničnom opstruktivnom bolesti pluća ne zavisi od&nbsp;dužine lečenja hronične opstruktivne bolesti pluća.&nbsp;Dokazano je da učestalost&nbsp; metaboličkog sindoma&nbsp;nije veća kod bolesnika kojima je dijagnoza bolesti postavljena pre vi&scaron;e od pet godina i koji se od HOBP&nbsp;leče duže od pet godina. Na osnovu rezultata koje&nbsp;smo dobili u na&scaron;em istraživanju zaključili smo da&nbsp;hronične plućne bolesti, bronhiektazije i hronična&nbsp;opstruktivna bolest pluća, predstavljaju stanja sa povi&scaron;enim kardiometaboličkim rizikom.</p><p>&nbsp;</p> / <p>Chronic inflammatory diseases of the respiratory&nbsp;organs are one of the leading morbidity and&nbsp;mortality causes all over the world. Despite the&nbsp;steady advance in scientific research, discovery&nbsp;of&nbsp; the disease-progression-contributing molecular<br />and cellular mechanisms, introduction of novel&nbsp;prognostic biomarkers, new detection methods of&nbsp;infectious agents, application of&nbsp; new, potent&nbsp;bronchodilation, anti-inflammatory and anti-infectious drugs,&nbsp; a constant&nbsp; increase in&nbsp; the&nbsp;number of the affected and deceased from chronic&nbsp;pulmonary diseases has still been permanently<br />evidenced in the 21st century. In a modern&nbsp;concept, the chronic obstructive pulmonary<br />disease (COPD) is understood as a heterogenous&nbsp;disorder associated with numerous comorbidities&nbsp;and systemic manifestations. Common risk factors&nbsp;represent the basis for concomitant chronic&nbsp;diseases to develop. Comorbidities and acute&nbsp;exacerbations contribute to the overall disease&nbsp;severity. As a COPD may develop extrapulmonary manifestations as well, each&nbsp;patient should be evaluated for systemic&nbsp;manifestations and comorbidities. The 2011&nbsp;update of the &bdquo;Global Strategy for Chronic&nbsp;Obstructive Lung Disease Diagnosis,&nbsp;Management, and Prevention &ndash;GOLD&rdquo; lists the&nbsp;following comorbidities to be actively searched&nbsp;for: cardiovascular diseases, skeletal muscle<br />dysfunction, metabolic syndrome, osteoporosis,&nbsp;depression, and lung cancer. Bronchiectases&nbsp;represent a chronic lung disorder marked by&nbsp;VII excessively dilated bronchial lumen&nbsp; induced by&nbsp;weakened or destructed muscular and elastic&nbsp;components of the bronchial wall, reduced mucus&nbsp;clearance, and recurrent respiratory infections.&nbsp;Bronchiectases and COPD have some clinical&nbsp;features in common. The metabolic syndrome is a&nbsp;group of metabolic disorders which increase the&nbsp;risk of&nbsp; cardiovascular diseases and type 2&nbsp;diabetes. In our investigation, we utilized the&nbsp;NCEP HATPIII definition of the metabolic&nbsp;syndrome based on the presence of three of five&nbsp;components: abdominal obesity (&gt; 102 cm and &gt;<br />88 cm waist&nbsp; measure for males and females&nbsp;respectively), elevated (&gt;1.7 mmol/l) triglyceride&nbsp;levels on an empty stomach, or a former history of&nbsp;the disorder treatment, reduced&nbsp; HDL cholesterol&nbsp;(&lt; 1.03 mmol/l and &lt;1.29 mmol/l for males and&nbsp;females respectively), or a former history of the&nbsp;disorder treatment, elevated systolic blood<br />pressure of &gt;130 mmHg and/or diastolic blood&nbsp;pressure of &gt; 85 mmHg, or a former history of&nbsp;treated hypertension, elevated glucose levels&nbsp; (&gt;5.6 mmol/l), or already existing type 2 diabetes&nbsp;mellitus. The investigation has been carried out in<br />the Institute for Pulmonary Diseases of&nbsp;Vojvodina, Sremska Kamenica, aimed at 1)<br />establishing the frequency of the metabolic&nbsp;syndrome and its components among the patients&nbsp;with COPD and bronchiectases; 2) analyze and&nbsp;compare the frequency of metabolic syndrome&nbsp;and its components in the examined groups related&nbsp;to the patients&rsquo; sex, age, and COPD treatment&nbsp;length. The study included 193 subjects, 163 of&nbsp;whom suffered from COPD and bronchiectases,&nbsp;classified into three groups: COPD patients (n=55,&nbsp;Group 1), patients with bronchiectases (n=50,&nbsp;Group 2), and patients with concurrent COPD and&nbsp;bronchiectases (n=58, Group 3). The control&nbsp;group, designated as Group 4, included 30&nbsp;subjects&nbsp; free of bronchiectases and COPD, so the&nbsp;total of 193 subjects were included in the&nbsp;investigation. The NCEP/ATP III criteria<br />established metabolic syndrome frequency among&nbsp;the patients with chronic respiratory diseases&nbsp;(COPD, bronchiectases, and concomitant COPD&nbsp;and bronchiectases) amounted to 37.3 % . The&nbsp;metabolic syndrome was more frequent in the&nbsp;patients with COPD and/or bronchiectases than in&nbsp;the control group patients free of any chronic&nbsp;respiratory disease. The metabolic syndrome was&nbsp;VIII confirmed in 38.2% of COPD patients, 54% of the&nbsp;patients with bronchiectases, and in 36.2% of the<br />patients with&nbsp; concomitant COPD and&nbsp;bronchiectases. The mean number of the<br />metabolic syndrome components was&nbsp; 2.18 in&nbsp;COPD patients,&nbsp;&nbsp; 2.56 in patients with<br />bronchiectases, and 2.1 in patients with&nbsp;concomitant COPD and bronchiectases. The<br />metabolic syndrome components were neither&nbsp;more frequent, nor statistically higher in the&nbsp;patients with concomitant COPD and&nbsp;bronchiectases as compared to the patients with a&nbsp;single presence of any of the two diseases. The&nbsp;difference in the single values of the metabolic&nbsp;syndrome components and the frequency of&nbsp;certain components in the examined groups of the&nbsp;patients with chronic pulmonary diseases was not&nbsp;statistically significant. Among the patients with&nbsp;chronic respiratory diseases, no correlation was&nbsp;observed between the metabolic syndrome&nbsp;frequency and the patients&rsquo; sex or age. The&nbsp;metabolic syndrome was not confirmed to be&nbsp;more frequent in males, or in&nbsp;&nbsp; &gt;65 yr old patients,&nbsp;as compared to younger patients. Among COPD<br />patients, no correlation was registered between the&nbsp;metabolic syndrome frequency and&nbsp;&nbsp; COPD&nbsp;treatment duration. It was confirmed that the&nbsp;metabolic syndrome frequency was not higher in&nbsp;the patients with &lt;5Hyear long COPD treatment<br />than in those treated for COPD longer. On the&nbsp;basis of the results obtained in our investigation,&nbsp;we conclude that chronic respiratory diseases,&nbsp;COPD and &nbsp;bronchiectases, are the conditions with&nbsp;a higher cardiometobolic risk.</p>

<p>Uvod: Bronhopulmonalna displazija (BPD) je najče&scaron;ća i najteža respiratorna posledica prematuriteta. Utvrđivanje najznačajnijih faktora rizika za nastanak BPD kod novorođenčadi porođajne mase (PM) ispod 1500g može omogućiti procenu rizika za&nbsp; nastanak bolesti i identifikaciju novorođenčadi u visokom riziku, &scaron;to je važno za pružanje informacija roditeljima o prognozi,&nbsp; planiranje preventivnih i terapijskih mera i stratifikovanje novorođenčadi koja su u riziku za sprovođenje budućih istraživanja. Cilj: Utvrđivanje incidencije, stepena težine BPD, smrtnosti, identifikacija najznačajnijih prenatalnih i postnatalnih faktora rizika za nastanak BPD, konstrukcije modela predikcije za nastanak BPD. Materijal i metode: Istraživanje je sprovedeno na 504&nbsp; prevremeno rođene novorođenčadi PM&lt;1500g koja su rođena u porodili&scaron;tima u AP Vojvodini i lečena u tercijarnom Centru za neonatologiju i intenzivnu negu i terapiju, na Institutu za zdravstvenu za&scaron;titu dece i omladine Vojvodine u periodu od&nbsp; 2006.-2011. godine. Retrospektivno je analizirano prisustvo BPD, prema stepenima težine, smrtnost. Podaci su izdvojeni iz&nbsp; istorija bolesti za svako novorođenče, 30 potencijalnih prenatalnih i postnatalnih faktora je opisano deskriptivnom i univarijantnom statistikom. Statstički najznačajniji faktori su uneti u multifaktorsku logističku regresionu analizu u cilju&nbsp; konstrukcije prediktivnih modela za nastanak BPD u 1.,14. i 21. danu neonatalnog života. Podaci su obrađeni u StatSoft-ovom&nbsp; programskom paketu Statistica 10.0.&nbsp; Validacija modela predikcije je sprovedena u prospektivnom delu istraživanja, na 100&nbsp;&nbsp;&nbsp; prevremeno rođene novorođenčadi&lt;1500g, u periodu od 2012-2013. godine. Rezultati: U retrospektivnom delu&nbsp; istraživanja,&nbsp; od 504&nbsp; novorođenčeta PM&lt;1500 grama, umrlo je 17.65%, BPD je imalo 45.43% (blagu BPD 19.44%, srednje te&scaron;ku 19.84%,&nbsp; te&scaron;ku&nbsp; 6.15%), srednje te&scaron;ku i&nbsp; te&scaron;ku 25.99%.Antenatalna primena kortikosteroida je zastupljena u 47.02%, surfaktant&nbsp;&nbsp; je&nbsp;&nbsp; primenjen kod 69.78% novorođenčadi. Najznačajniji prenatalni prediktivni faktor rizika za nastanak BPD/smrtnog ishoda je horioamnionitis (OR 5.72; 95% CI 3.42-9.62), dok su protektivni faktori: prenatalna primene kortikosteroida (OR&nbsp; 0.41;&nbsp; 95%CI&nbsp; 0.29-0.60), porođaj carskim rezom (OR&nbsp; 0.24; 95% CI 0.16-0.36). Najznačajniji&nbsp; postnatalni prediktivni faktori rizika su: GS&nbsp; (p&asymp;0.00), PM (p&asymp;0.00), reanimacija u porođajnoj sali (OR 7.01; 95% CI 4.12-12.01), rana&nbsp; neonatalna&nbsp; sepsa&nbsp; (OR&nbsp; 7.35;&nbsp; 95%CI&nbsp; 3.79-14.58), RDS&nbsp; (p&asymp;0.00), primena surfaktanta (OR13,3;95%CI 8,2 - 21,67), DAP (OR 4.12; 95%CI&nbsp; 2.47-6.89),&nbsp; dok&nbsp; je&nbsp; ženski&nbsp; pol&nbsp; protektivan (OR&nbsp; 0.61; 95% CI 0.42-0.89). FiO2 i IPPV su u svim posmatranim danima značajni faktori rizika. Primena IPPV u 1. danu (OR 10.71;&nbsp; 95% CI 6.67-17.26); u ostalim danima rizik od BPD raste prema rastućoj invazivnosti respiratorne&nbsp; potpore.&nbsp; Konstruisani su modeli&nbsp; predikcije za 1, 14 i 21. dan života, modeli imaju visoku prediktivnu vrednost: ukupan procenat uspe&scaron;nosti&nbsp; modela je 84.26%-90.80%, modeli sa ne&scaron;to većim uspehom predviđaju&nbsp;&nbsp; prisustvo (85.36%-94.12%), nego odusustvo BPD (81.72-86.56%). OR modela je 28.07-103.04. Modeli su uspe&scaron;no validirani&nbsp; na 102 pacijenta sa ukupnim procentom uspe&scaron;nosti (82-90%), PPV (0.86-0.94) i NPV (0.76-0.87). Zaključak:&nbsp; Kori&scaron;ćenjem&nbsp; prenatalnih i postnatalnih kliničkih podataka moguće je predvideti nastanak BPD ili smrtnog ishoda.</p> / <p>Introduction: Bronchopulmonary dysplasia (BPD) is the most common serious pulmonary morbidity in very low birth weight (VLBW) infants. It is of clinical importance to determine clinical variables that are associated with BPD in order to identify infants who are at risk of developing BPD; it contributes to BPD prevention, may enable prognostic information for parents and future studies design. Objective: The aim of this study was to determine the incidence and severity of BPD, mortality rate in VLBW infants, to identify prenatal and postnatal predictive risk factors for bronchopulmonary dysplasia and competing outcome of death and to develop predictive models. Materials and Methods: Study was conducted in 504 VLBW infants born in the maternity hospitals in Vojvodina and admitted to tertiary Center for newborn and neonatal intensive care at the Institute for Child and Youth Health Care of Vojvodina, from January 2006. to December 2011. Data were retrospectively collected from clinical records for outcomes BPD or death; prenatal and postnatal factors associated with BPD were collected at three postnatal ages and examined by descriptive and univariate statistics; factors that were significantly associated with BPD and/or death were entered into a multivariate logistic regression analysis for develop predictive models. Data were analyzed using StatSoft&#39;s software package Statistica 10.0. Validation of the models were conducted in a prospective study in 102 VLBW infants born from January 2012. to December 2013. Results: There were 504 very low birth weight infants who were eligible for this study, 17.65% died, 45.43% developed BPD (mild BPD 19.44%, moderate 19.84%, severe 6.15%), moderate and severe 25.99%. The mean birth weight for the cohort was 1125.6&plusmn;280.9g, the mean gestation age was GS 28,78&plusmn;3,01, 49.21% were male. Surfactant received 69.78%, antenatal steroids 47.02% newborns. Key risk factors for BPD and/or death were: chorioamnionitis and maternal infections at delivery (OR 5.72; 95% CI 3.42-9.62); protective prenatal factors were: antenatal corticosteroid therapy (OR 0.41; 95%CI 0.29-0.60), cesarean delivery (OR 0.24; 95% CI 0.16-0.36). Postnatal rick factors were: GS (p&asymp;0.00), birth weight (p&asymp;0.00), delivery room resuscitation (OR 7.01; 95% CI 4.12-12.01), early neonatal sepsis (OR 7.35; 95%CI 3.79-14.58), RDS (p&asymp;0.00), surfactant (OR13,3;95%CI 8,2 - 21,67), DAP (OR4.12; 95% CI 2.47-6.89), while female gender was protective (OR 0.61; 95% CI 0.42-0.89). At each time point studied, FiO2 was significantly higher in BPD/death, as well as respiratory support; on the first day invasive respiratory support was significantly associated with BPD/death (IPPV and HFOV) (OR 10.71; 95% CI 6.67-17.26), in other days BPD was associated with increasing invasiveness of respiratory support. In multifactorial logistic regression analysis separately predictive models were developed at three postnatal ages, at 1st, 14th and 21st day. Models had high predictive performance: total success of the models were 84.26% - 90.80%, models successfully predicted the presence of BPD in 85.36% -94.12%, absence of the BPD in 81.72 - 86.56% cases. OR of models were 28.07-103.04. The models were successfully validated on 102 patients with a total percentage of success 82 - 90%, with PPV 0.86-0.94 and NPV 0.76-0.87. Conclusion: Using prenatal and postnatal clinical data it is possible to predict the development of BPD and/or death in very low birth weight infants. It is very important to identify risk factors for BPD development in order to decrease the incidence of BPD and mortality rate.</p>

<p>Predmet istraživanja ovog rada je ambijent ekonomije znanja i<br />poslovanje malih i srednjih preduzeća u tom ambijentu. Problem<br />istraživanja je analiza faktora koji utiču na uspešnost malih i<br />srednjih preduzeća. Cilj istraživanja je da se utvrde ključni faktori<br />uspešnosti malih i srednjih preduzeća u Srbiji kako bi se<br />definisale mere za povećanje konkurentnosti ovog sektora i razvio<br />model upravljanja malim i srednjim preduzećima u ekonomiji znanja na<br />bazi ključnih faktora uspešnosti. Vrednost dobijenih rezultata<br />proističe iz cilja istraživanja u okviru ove disertacije, koji u širem<br />smislu podrazumeva pružanje informacija naučnoj i stručnoj javnosti<br />koje mogu doprineti daljem razvoju sektora MSP i boljem upravljanju<br />na bazi ključnih faktora uspešnosti.</p> / <p>The subject of this work is the environment of the knowledge economy and<br />the business of small and medium enterprises in this environment. The<br />problem of this research is to analyze the factors affecting the performance<br />of small and medium-sized enterprises. The aim of the research is to identify<br />the key success factors of small and medium-sized enterprises in Serbia in<br />order to define measures to increase the competitiveness of the sector and<br />developed a model of management of small and medium enterprises in the<br />knowledge economy based on the key factors of success. The value of the<br />results of this study arises from the research objectives within the framework<br />of this thesis, which in a broader sense means providing information to the<br />scientific and professional community that can contribute to the further<br />development of the SME sector and better management of SMEs on the<br />basis of the key success factors</p>

<p>Uvod. Kardiovaskularne bolesti kao deo grupe hroničnih nezaraznih bolesti predstavljale su i predstavljaju vodeći uzrok obolevanja i umiranja u svetu. Brojni naučni dokazi potvrđuju da je arterijska hipertenzija glavni kardiovaskularni faktor rizika, a da postignute vrednosti krvnog pritiska niže od 140/90mmHg značajno smanjuju kardiovaskularni rizik, odnosno pojavu kardiovaskularnih događaja, prvenstveno infarkta miokarda i moždanog udara. Arterijska hipertenzija je najzastupljenije stanje koje se viđa u ustanovama primarne zdravstvene za&scaron;tite, a mere prevencije, rano dijagnostikovanje, lečenje i kontrola arterijske hipertenzije predstavljaju javno-zdravstveni izazov u svim zemljama sveta. Ciljevi. Ciljevi istraživanja su utvrđivanje prevalencije arterijske hipertenzije koja je pod kontrolom; utvrđivanje prevalencije i povezanosti metaboličkih faktora sa ishodom u kontroli krvnog pritiska; utvrđivanje prevalencije i povezanosti nezdravih stilova života sa ishodom u kontroli krvnog pritiska; utvrđivanje prediktora lo&scaron;e kontrole krvnog pritiska i izračunavanje 10-godi&scaron;enjeg kardivaskularnog rizika. Metode. U studiju preseka (prevalencije) uključeno je 373 ispitanika oba pola starosti od 45 do 75 godina sa dijagnozom arterijske hipertenzije u kartonu koji su u periodu od oktobra 2015. godine do februara 2016. godine dolazili kod svog izabranog lekara. Prikupljanje podataka obavljeno je merenjem krvnog pritiska, antropometrijskim merenjima, biohemijskim analizama i anketiranjem popunjavanjem upitnika. Rezultati. Uzorak ispitanika je činilo 55% žena i 45% mu&scaron;karaca prosečne starosti 59&plusmn;6,3 godine. Utvrđena je niska učestalost arterijske hipertenzije pod kontrolom od 39,1%, a visoka učestalost metaboličkih faktora (44,5% predgojaznosti, 34% gojaznosti, 29% &scaron;ećerne bolesti, 88,2% povi&scaron;enih masnoća i 41,8% metaboličkog sindroma) kao i njihova povezanost sa ishodom u kontroli krvnog pritiska jer su ispitanici sa nekontrolisanim krvnim pritiskom najče&scaron;će imali dva faktora rizika (40,5%), dok su ispitanici sa kontrolisanim krvnim pritiskom najče&scaron;će imali jedan faktor rizika (45,9%). Utvrđeno je da su prosečne vrednosti sistolnog, dijastolnog pritiska i pulsa bile značajno (p&lt;0,001) niže u grupi sa kontrolisanim pritiskom kao i da su ispitanici sa nekontrolisanim pritiskom imali značajno veći obim struka (p=0,006), metabolički sindrom (p&lt;0,001) i značajno če&scaron;će pili veći broj lekova (p&lt;0,001). Utvrđena je visoka učestalost pu&scaron;enja (26,3%) i visoka učestalost sedentarnog načina života (76,7%) kao i da znanja, stavovi i pona&scaron;anja ispitanika u vezi faktora rizika (pu&scaron;enja, konzumiranja alkohola, fizičke neaktvnosti i prekomerne upotrebe soli) nisu na zadovoljavajućem nivou. Kao nezavisni prediktori arterijske hipertenzije koja nije pod kontrolom dobijeni su obim struka, telesna masa, indeks telesne mase, starost, vrednost pulsa, broj lekova koje ispitanici piju, pasivno pu&scaron;enje, nesvesnost o postojanju arterijske hipertenzije, neznanje o &scaron;tetnosti konzumiranja prekomerne količine alkohola, nepreležan infarkt miokarda i moždani udar. Izračunato je da je u visokom i veoma visokom riziku od neželjenih kardiovaskularnih događaja u desetogodi&scaron;njem periodu 2,7% ispitanika sa arterijskom hipertenzijom bez dijabetesa i 22,2% hipertenzivnih ispitanika sa dijabetesom. Zaključak. Potrebno je sprovođenje javno-zdravstveno vaspitnih i promotivnih aktivnosti u cilju povećanja znanja, promene stavova i pona&scaron;anja kod populacije sa arterijskom hipertenzijom usled lo&scaron;e kontrole krvnog pritiska i prisustva visoke učestalosti pridruženih faktora rizika koji utiču na njegovu kontrolu.</p> / <p>Introduction. Cardiovascular diseases, as part of a group of chronic noncommunicable diseases, have been and still are the leading cause of morbidity and mortality in the world. Numerous scientific proofs confirm that arterial hypertension is a major cardiovascular risk factor and that the achieved blood pressure values lower than 140/90mmHg significantly reduce cardio-vascular risk, or the appearance of cardio-vascular events, mainly myocardial infarction and stroke. Arterial hypertension is the most common condition that is seen in primary health care institutions and preventive measures, early diagnosis, treatment and control of arterial hypertension are a public health challenge in all countries of the world. Objectives. The objectives of the research were to determine the prevalence of arterial hypertension which is controlled; to determine the prevalence and correlation of the metabolic factors with the outcome in blood pressure control; to determine the prevalence and correlation of unhealthy lifestyles with the outcome in blood pressure control; to determine the predictors of poor blood pressure control and calculate a 10-year cardiovascular risk. Methods. The cross-sectional study (of prevalence) included 373 respondents of both sexes aged 45 to 75 years diagnosed with arterial hypertension who in the period from October 2015 to February 2016 visited their chosen doctor. Data collection was performed by measuring blood pressure, anthropometric measurements, biochemical analyses and surveying by filling out a questionnaire. Results. The sample consisted of 55% women and 45% men, of mean age of 59&plusmn;6.3 years. The results showed low incidence of arterial hypertension under control of 39.1%, and high incidence of metabolic factors (44.5% of overweight, 34% of obesity, 29% of diabetes mellitus, 88.2% of elevated fat and 41.8% of the metabolic syndrome) as well as their association with the outcome in blood pressure control as the respondents with uncontrolled blood pressure usually had two risk factors (40.5%), while the group with controlled blood pressure usually had one risk factor (45.9%). It was found that the average values of systolic, diastolic blood pressure and heart rate were significantly (p&lt;0.001) lower in the group with controlled blood pressure, as well as that the respondents with uncontrolled pressure had a significantly greater waist circumference (p=0.006), the metabolic syndrome (p&lt;0.001) and more often drunk greater number of medicines (p&lt;0.001). There was a high prevalence of smoking (26.3%) and a high incidence of sedentary lifestyle (76.7%) and it was found that knowledge, attitudes, and behaviors of the respondents related to risk factors (smoking, alcohol consumption, physical inactivity and excessive use of salt) were not satisfactory. As independent predictors of arterial hypertension which was not under the control, the study obtained waist circumference, body weight, body mass index, age, heart rate value, the number of medicines that the respondents drunk, second-hand smoking, unawareness of the existence of arterial hypertension, inexperience on the harmful effects of excessive amounts of alcohol, not overcome myocardial infarction and stroke. It was calculated that 22.2% of hypertensive respondents with diabetes and 2.7% of respondents with arterial hypertension without diabetes were in the high and very high risk of adverse&nbsp; Conclusion. It is necessary to implement public-health educational and promotional activities in order to increase the knowledge, changes in the attitudes and behavior of the population with arterial hypertension due to the poor control of blood pressure and the presence of the high incidence of associated risk factors affecting its control.</p>

<p>Uvod: Kardiovaskularne bolesti predstavljaju vodeći uzrok obolevanja i umiranja savremenog čoveka i vodeći su javno-zdravstveni problem u svetu i kod nas. Brojna istraživanja sugeri&scaron;u da se mediteranski način ishrane povezuje sa smanjenjem rizika za nastanak i razvoj kardiovaskularnih bolesti i drugih masovnih nezaraznih bolesti kao i smanjenjem stope ukupnog mortaliteta. Cilj istraživanja: Utvrditi stepen pridržavanja mediteranskom načinu ishrane kod obolelih od akutnog koronarnog sindroma i kod osoba sa utvrđenim rizikom za nastanak kardiovaskularnih bolesti, upotrebom validovanog skora mediteranske ishrane &ndash; MedDiet skora. Takođe, cilj istraživanja je bio da se utvrdi da li postoji značajna razlika u vrednostima biohemijskih i kliničkih faktora rizika za razvoj kardiovaskularnih bolesti između dve posmatrane grupe ispitanika, kao i da se odredi granična vrednost MedDiet skora između poželjnog i rizičnog načina ishrane za nastanak akutnog koronarnog sindroma. Metod: Istraživanje je sprovedeno kao analitička studija preseka na uzorku od 294 ispitanika (146 žena i 148 mu&scaron;karaca), starosti od 30 do 82 godine. Istraživanje je sprovedeno u vremenskom periodu od 07.02.2016. godine do 16.03.2017. godine. Prvu grupu činili su ispitanici kod kojih je&nbsp; dijagnostikovan akutni koronarni sindrom, koji su hospitalizovani u Institutu za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici, dok su drugu grupu činili ispitanici kod kojih je utvrđeno prisustvo najmanje jednog faktora rizika za nastanak kardiovaskularnih bolesti, bez klinički manifestne koronarne bolesti, koji su se javili na pregled u Savetovali&scaron;te za pravilnu ishranu, Instituta za javno zdravlje Vojvodine u Novom Sadu. Kod svih učesnika u studiji izvr&scaron;ena su: antropometrijska merenja, merenje arterijskog krvnog pritiska, odgovarajuće biohemijske analize, EKG i anketiranje upotrebom posebno pripremljenog upitnika, u čijem sastavu se nalazio i MedDiet skor &ndash; validovan skor system za procenu stepena zastupljenosti mediteranskog načina ishrane kod pojedinca. Rezultati istraživanja: Srednja vrednost MedDiet skora ispitanika bez akutnog koronarnog sindroma bila je 27,48&plusmn;6,59, dok je srednja vrednost MedDiet skora ispitanika sa akutnim koronarnim sindromom bila 20,53&plusmn;4,01. Razlika srednjih vrednosti MedDiet skora između dve grupe ispitanika bila je statistički značajna (p=0,029). Ispitivanjem prediktivnih vrednosti pojedinih varijabli utvrđeno je da su MedDiet skor i glikemija na&scaron;te odlični markeri za akutni koronarni sindrom (AUROC=0,815, p&lt;0,0005 i AUROC=0,829, p&lt;0,0005, respektivno). Rezultati istraživanja su pokazali da konzumiranje pojedinih namirnica iz kategorija definisanih MedDiet skorom (voće, povrće, živinsko meso i maslinovo ulje) može doprineti smanjenju rizika za nastanak akutnog koronarnog sindroma. Konzumiranje crvenog mesa i mesnih prerađevina povećava rizik od pojave akutnog koronarnog sindroma. Utvrđena granična vrednost MedDiet skora iznosila je 22,5. Vrednosti MedDiet skora &le;22,5 predstavljaju faktor rizika za nastanak akutnog koronarnog sindroma, dok vrednosti MedDiet skora &gt;22,5 ukazuju na smanjen rizik za nastanak akutnog koronarnog sindroma. Multivarijantnom regresionom analizom pokazano je da na pojavu akutnog koronarnog sindroma utiču sledeći faktori rizika: godine starosti 1,063 (1,270-1,819), mu&scaron;ki pol 4,071 (1,901-8,719), pu&scaron;enje 3,067 (1,322-7,114), indeks telesne mase 0,902 (0,839-0,970), sistolni pritisak 1,020 (1,003-1,037), glikemija na&scaron;te 1,520 (1,025-1,101) i MedDiet skor 0,783 (0,722-0,849). Zaključak: Akutni koronarni sindrom predstavlja značajan javno-zdravstveni problem odraslog stanovni&scaron;tva u Republici Srbiji na &scaron;ta ukazuju visoke prevalencije u populaciji. Rezultati sprovedenog istraživanja pokazuju da je i diskretnim povećanjem unosa namirnica koje predstavljaju osnovu mediteranskog načina ishrane moguće postići značajne zdravstvene koristi. Ovi rezultati mogu predstavljati okvir za razvoj lokalnog skoring sistema ishrane prikladnog za nemediteransko područje, kao i modela za procenu rizika za nastanak akutnog koronarnog sindroma u na&scaron;oj populaciji.</p> / <p>Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality of a modern society and are major public health problem in our country and also worldwide. Numerous studies suggest that the Mediterranean diet is associated with a reduction in the risk of developing cardiovascular diseases and other non-communicable diseases, as well as reduction in the overall mortality rate. Aim: To determine the degree of Mediterranean diet complience in subjects with acute coronary syndrome and subjects with an established risk for developing cardiovascular diseases, using validated Mediterranean diet score - MedDiet. Also, the aim of the study was to determine whether there is a significant difference in the values of the&nbsp; biochemical and clinical risk factors for the development of cardiovascular diseases between the two observed groups of subjects, and to determine the cut-off value of the MedDiet score between the favorable and unfavorable dietaty pattern for the development of acute coronary&nbsp; syndrome. Method: The study was conducted as an analytical cross-sectional study with enrollment of 294 subjects (146 women and 148 men), 30 to 82 years of age. The research was conducted during the period from 02/07/2016 until 03/16/2017. The first group of subjects consisted of patients diagnosed with acute coronary syndrome who were hospitalized at the Institute for Cardiovascular Diseases Vojvodina in Sremska Kamenica. The second group was comprised of subjects with established at least one major risk factor for the development of cardiovascular diseases but without clinically manifest coronary artery disease, who came to the medical examination of the Counseling Center for Proper Nutrition, Institute of Public Health of Vojvodina in Novi Sad. Among all participants in the study the following examinations were conducted: anthropometric measurements, arterial blood pressure measurements, appropriate biochemical analysis, ECG and surveys using a specially prepared questionnaire, which included MedDiet score - validated score system for assessing the degree of compliance with Mediterranean dietary pattern among subjects. Results of the study: The average value of the MedDiet score among subjects without acute coronary syndrome was 27.48 &plusmn; 6.59, while the average value of MedDiet score among subjects with acute coronary syndrome was 20.53 &plusmn; 4.01. The difference in MedDiet average values between the two groups of subjects was statistically significant (p = 0.029). By examining the predictive values of individual variables, it was shown that MedDiet score and fasting blood sugar were excellent markers for acute coronary syndrome (AUROC = 0.815, p&lt;0.0005 and AUROC = 0.829, p &lt;0.0005, respectively). The results of the study showed that the consumption of certain foods in the categories defined by MedDiet score (fruits, vegetables, poultry, and olive oil) can contribute to reduction of the risk for developing acute coronary syndrome. On the other hand, consuming red meat and meat products increased the risk of acute coronary syndrome. The established cut-off value for MedDiet score was 22.5. MedDiet score &le;22.5 practicaly indicated greater risk for the development of acute coronary syndrome, while MedDiet score&gt; 22.5 indicated reduced risk for the development of acute coronary syndrome. Multivariate regression analysis showed that acute coronary syndrome is affected by the following risk factors: age 1,063 (1,270-1,819), male gender 4,071 (1,901-8,719), smoking 3,067 (1,322-7,114), body mass index 0,902 (0.839-0.970 ), systolic blood pressure 1.020 (1.003-1.037), fasting blood sugar 1.520 (1.025-1.101) and MedDiet score 0.783 (0.722- 0.849). Conclusion: Acute coronary syndrome is a major public health problem in the adult population of the Republic of Serbia, as indicated by its high prevalence. The results of the conducted research show that discrete increase in food intakes of foods which represent the basis of the Mediterranean diet, can lead to significant health benefits. These results can represent a framework for the development of a local scoring system for a non-mediterranean area, and also for creation of risk assessment model for acute coronary syndrome in our population.</p>

<p>Tromboza danas, u većini razvijenih zemalja, predstavlja vodeći uzrok obolevanja i umiranja. Poslednjih godina veoma aktuelna su istraživanja venskog tromboembolizma, obzirom da je incidenca ovog oboljenja 2/1000 osoba godi&scaron;nje, a njegov razvoj posledica udruženog delovanja vi&scaron;e genetskih i stečenih faktora rizika. &Scaron;to preciznije prepoznavanje i sagledavanje &scaron;to većeg broja ovih faktora osnovni je cilj u borbi, kako protiv prve epizode venske tromboze, tako i protiv recidiva ove bolesti. Brojni faktori rizika već su prepoznati kao sastavne karike patofiziolo&scaron;kog lanca venskog trombotskog procesa, ali je evidentno da otkrića mnogih od njih tek predstoje. Među najaktulenijim istraživanjima na ovom polju nalazi se i ispitivanje uloge poremećaja fibrinoliznog mehanizma u venskoj tromboembolijskoj bolesti. Iako su već pruženi dokazi da suprimirana fibrinolizna aktivnost povećava rizik od nastanka ovog oboljenja, jo&scaron; uvek postoje brojna otvorena pitanja, koja se pre svega odnose na ulogu pojedinačnih činilaca fibrinoliznog mehanizma u venskoj trombozi, kao i na globalnu ulogu fibrinoliznog mehanizma u različitim tipovima i lokalizacijama venske trombotske bolesti. Pored toga, ispitivanje uticaja pojedinih genskih mutacija na pojadinačne činioce fibrinoliznog mehanizma, njegovu globalnu funkcionalnost i posredno na rizik za nastanak venske tromboze, takođe zaokuplja pažnju stručne javnosti, obzirom na nekonzistentnost rezultata dobijenih studijama koje se bave ovom problematikom. Cilj ovoga istraživanja je ispitivanje kako globalne funkcionalnosti fibrinoliznog mehanizma, tako i njegovih pojedinačnih činilaca, kod bolesnika sa različitim tipovima i lokalizacijama venske tromboze i poređenje ovih parametara sa njihovim vrednostima u zdravoj populaciji. Pored toga, cilj istraživanja je i ispitivanje zastupljenosti 4G/5G PAI-1 polimorfizma kod bolesnika sa venskom trombozom u poređenju sa zdravim osobama. Ispitivanu grupu je sačinjavalo 100 bolesnika koji su doživeli trombozu dubokih vena a kontrolnu grupu je činilo 100 zdravih ispitanika, koji nikada nisu imali trombozni incident. Iz ispitivanja su isključene: osobe sa prethodno dokazanim poremećajem hemostaznog mehanizma, osobe koje uzimaju lekove za koje se zna da mogu imati uticaja na hemostazni mehanizam, osobe koje su imale akutnu bolest u momentu uzorkovanja krvi ili 6 nedelja pre toga, osobe sa malignitetom, trudnice, osobe sa težim du&scaron;evnim bolestima, bolestima jetre i bubrega, autoimunim bolestima, ispitanici koji su odbili da potpi&scaron;u pristanak informisanog ispitanika. Kao test za procenu globalne funkcionalnosti fibrinoliznog mehanizma kori&scaron;teno je euglobulinsko vreme lize koaguluma, dok su od pojedinačnih činilaca određivani: tkivni aktivator plazminogena (t-PA) i trombinom aktivi&scaron;ući fibrinolizni inhibitor (TAFI) - ELISA metodom, kao i inhibitor aktivatora plazminogena-1 (PAI-1) - metodom hromogenog substrata. Genetskim ispitivanjem je utvrđivano prisustvo PAI-1 4G/5G genskog polimorfizma. Prema rezultatima istraživanja kod 56% bolesnika bila je prisutna spontana venska tromboza, dok je 44% njih imalo trombozu provociranu jednim od priznatih faktora rizika. U odnosu na lokalizaciju venskog tromboznog procesa proksimalna venska tromboza bila je prisutna kod 63% bolesnika, izolovana distalna venska tromboza kod 29% bolesnika, a atipično lokalizovana venska tromboza kod 8% bolesnika. Posmatrajući zastupljenost pojedinih faktora rizika uočili smo da je značajno vi&scaron;i procenat osoba sa hipertenzijom bio prisutan u grupi bolesnika sa primarnom trombozom dubokih vena u odnosu na grupu bolesnika sa provociranom trombozom dubokih vena (61% vs.16%; p=0.000). &Scaron;to se funkcionalnosti fibrinoliznog mehanizma tiče, prema na&scaron;im rezultatima bolesnici koji su doživeli trombozu dubokih vena imaju značajno duže vreme lize koaguluma, odnosno suprimiranu funkcionalnost fibrinolize u poređenju sa zdravim kontrolama (204.34&plusmn;51.24 vs. 185.62&plusmn;42.30; p=0.011), a kada posmatramo podgrupe bolesnika u odnosu na lokalizaciju i vrstu venske tromboze uočavamo da podgrupa bolesnika sa izolovanom distalnom venskom trombozom ima značajno duže euglobulinsko vreme lize koaguluma u odnosu na kontrolnu grupu (218.32&plusmn;41.12 vs.185.62&plusmn;42.30: p=0.001), kao i bolesnici koji su imali provociranu vensku trombozu u poređenju sa kontrolama (208.18&plusmn;48.53 vs. 185.62&plusmn;42.30; p=0.018). Ispitivanjem pojedinačnih komponenti fibrinoliznog mehanizma do&scaron;li smo do rezultata da bolesnici koji su doživeli venski trombozni incident imaju značajno vi&scaron;e koncentracije TAFI u poređenju sa osobama koje nikada nisu imale vensku trombozu (19.70 ng/ml &plusmn; 5.17 vs.17.13 ng/ml &plusmn; 4.25; p=0.001). Poređenjem bolesnika sa provociranom trombozom dubokih vena i kontrolnih ispitanika uočili smo da bolesnici iz ove podgrupe imaju značajno vi&scaron;e vrednosti plazminogena u poređenju sa zdravim osobama (127.14 % &plusmn; 27.73 vs.117.09 % &plusmn; 24.49; p= 0.044), kao i značajno vi&scaron;e koncentracije t-PA (20.02 ng/ml &plusmn; 11.07 vs. 16.78 ng/ml &plusmn; 8.08; p=0.042). &Scaron;to se tiče TAFI, bolesnici sa distalnom trombozom dubokih vena u poređenju sa kontrolama (20.72 ng/ml &plusmn; 4.96 vs.17.13 ng/ml &plusmn; 4.25; p=0.001), kao i bolesnici sa proksimalnom trombozom dubokih vena u poređenju sa kontrolama (19.37 ng/ml &plusmn; 5.33 vs.17.13 ng/ml &plusmn; 4.25; p=0.013) imaju značajno vi&scaron;e koncentracije TAFI. Koncentracija ovog inhibitora fibrinoliznog procesa značajno je veća i kod bolesnika sa provociranom trombozom dubokih vena u poređenju s zdravim osobama (19.93 ng/ml &plusmn; 3.97 vs.17.13 ng/ml &plusmn; 4.25; p=0.000), kao i kod bolesnika sa primarnom trombozom dubokih vena u poređenju sa zdravim ispitanicima (19.53 ng/ml &plusmn; 5.97 vs.17.13 ng/ml &plusmn; 4.25; p=0.023). &Scaron;to se genetskih analiza tiče, u okviru grupe bolesnika imali smo 25% homozigotnih i 58% heterozigotnih nosilaca mutacije gena za PAI-1, dok 17% bolesnika nije imalo pomenutu gensku mutaciju. U okviru kontrolne grupe pak, bilo je 30% homozigotnih i 56% heterozigotnih nosilaca mutacije a 14% ispitanika nije imalo mutaciju. Nije uočena značajna razlika u zastupljenosti 4G/4G genotipa između bolesnika sa različitim lokalizacijama venskog trombotskog procesa (distalna DVT 29% vs. proksimalna DVT 21% vs. DVT retke lokalizacije 12%; p=0.501), kao ni u zastupljenosti ovoga genotipa kod provocirane i spontane tromboze dubokih vena (27% vs. 23%; p=0.642), niti kod izolovane tromboze dubokih vena u poređenju sa plućnom tromboembolijom (25% vs. 33%; p=0.735). Procena rizika za nastanak venske tromboze u odnosu na postojanje poremećaja globalne funkcionalnosti fibrinoliznog mehanizma, u odnosu na patolo&scaron;ke koncentracije pojedinih komponenti fibrinoliznog mehanizma, kao i u odnosu na postojanje 4G/4G mutacije u genu za PAI-1, pokazala je da suprimirana funkcionalnost fibrinoliznog mehanizma trostruko povećava rizik za nastanak tromboze dubokih vena (OR 3.02; CI 1.26-7.22), povi&scaron;en nivo PAI-1 nema uticaja na rizik od nastanka tromboze dubokih vena, na &scaron;ta ukazuje OR od 0.86 sa CI 0.59-1.25, povi&scaron;en nivo t-PA antigena ne utiče na rizik od nastanka tromboze dubokih vena (OR 1.53; CI 0.79-2.94), ali povi&scaron;ena koncentracija TAFI vi&scaron;e od dvostruko povećava ovaj rizik (OR 2.25; CI 1.16-4.35). Prema na&scaron;im rezultatima PAI-1 4G/4G genotip nema uticaja na rizik od nastanaka venske tromboze, &scaron;to potvrđuje OR koji iznosi 0.57 (0.27-1.20). Na osnovu dobijenih rezultata zaključujemo da bolesnici sa trombozom dubokih vena imaju suprimiranu funkcionalnost fibrinoliznog mehanizma u poređenju sa zdravim osobama, da je nivo t-PA antigena, kao i plazminogena značajno vi&scaron;i kod bolesnika sa provociranom venskom trombozom nego kod zdravih osoba, da nema razlike u koncentraciji PAI-1 između bolesnika sa venskom trombozom i zdravih osoba, ali da bolesnici sa trombozom dubokih vena, bez obzira na njenu lokalizaciju ili vrstu imaju značajno vi&scaron;e nivoe TAFI u poređenju sa zdravim ispitanicima. Pored toga možemo zaključiti da ne postoji razlika u zastupljenosti 4G/5G polimorfizma između bolesnika sa venskom trombozom i zdravih ispitanika. Konačno, možemo reći da na osnovu na&scaron;ih rezultata možemo zaključiti da suprimirana funkcionalnost fibrinoliznog mehanizma trostruko povećava rizik od nastanka tromboze dubokih vena, a povi&scaron;en nivo TAFI-a dvostruko povećava ovaj rizik, dok 4G/5G PAI-1 polimorfizam nema uticaja na rizik za nastanak venskog tromboembolizma.</p> / <p>Thrombosis is nowadays leading cause of morbidity and mortality worldwide. Lately, studies dealing with venous thromboembolism are very actual, since incidence of this disease is 2/1000 persons per year and its development is consequence of joint action of many different inherited and acquired risk factors. Precise recognition and understanding as many of those factors as possible represents imperative in fight against the first episode of venous thrombosis, and also against the recurrence of the disease. Numerous risk factors have been already recognized as constituent links of pathophysiological chain of venous thrombotic process, but it is also clear that the discovery of many of them are yet to come. Investigations of the role of fibrinolytic mechanism disorders in venous thrombosis are topical in the field. Although, we have some evidences that suppressed fibrinolytic activity increases the risk of this disease, still there are many open issues, especially those dealing with the role of individual factors of fibrinolytic mechanism in venous thrombosis, and with the role of global fibrinolytic function in different types and localizations of venous thrombotic disease. Further, investigation of the effects of gene mutations on individual fibrinolytic mechanism components, its global functionality and indirectly to the risk of venous thrombosis, also attracts the attention of experts, given the inconsistency of results obtained from studies dealing with this issue. The aim of this study was to evaluate fibrinolytic mechanism global functionality, as well as functionality of its integral individual components in patients with different venous thrombosis types and localizations, and to compare them with those of the healthy persons. In addition, the aim was to evaluate presence of 4G/5G PAI-1 polymorphism in patients with venous thrombosis compared with healthy subjects. The case group consisted of 100 patients with deep vein thrombosis and the control group consisted of 100 healthy subjects who had never had thrombotic incident. Exclusion criteria were: documented haemostatic disease, taking drugs proven to affect fibrinolytic function, acute illness within 6 weeks before blood sampling, malignancy, pregnancy, severe mental illness, kidney or liver diseases, autoimmune diseases, examinee refusal to sign the informed consent. We used euglobulin cloth lysis time test as test for global fibrinolytic mechanism function estimation, and also determined: t-PA and TAFI concentrations using ELISA method and PAI-1 concentrations using chromogenic substrate method. The presence of PAI-1 4G/5G gene polymorphism was determined by genetic testing. According to results 56% of patients had unprovoked and 44% had provoked venous thrombosis. Proximal venous thrombosis was present in 63% of cases, distal venous thrombosis in 29% of cases and atypical venous thrombosis in 8% of them. Significantly higher frequency of hypertension was present in patients with primary deep vein thrombosis than in the group of patients with provoked deep vein thrombosis (61% vs. 16%, p = 0.000). Patients who have experienced deep vein thrombosis had a significantly longer clot lysis time, and suppressed fibrinolysis function compared with healthy controls (204.34 &plusmn; 51.24 vs. 185.62 &plusmn; 42.30, p = 0.011). Also, this parameter was significantly longer in patients with isolated distal deep vein thrombosis compared with healthy controls (218.32&plusmn;41.12 vs. 185.62&plusmn;42.30: p=0.001), such as in patients with provoked venous thrombosis compared with controls (208.18&plusmn;48.53 vs. 185.62&plusmn;42.30; p=0.018). Patients with venous thrombosis had significantly higher TAFI concentrations in comparison with healthy volunteers (19.70 ng/ml &plusmn; 5.17 vs. 17.13 ng/ml &plusmn; 4.25; p=0.001). Patients with provoked venous thrombosis had significantly higher concentrations of plasminogen (127.14 % &plusmn; 27.73 vs. 117.09 % &plusmn; 24.49; p= 0.044) and t-PA (20.02 ng/ml &plusmn; 11.07 vs. 16.78 ng/ml &plusmn; 8.08; p=0.042), in comparison with controls. Regarding TAFI, we noticed that patients with isolated distal deep vein thrombosis have higher values of this parameter compered with healthy people (20.72 ng/ml &plusmn; 4.96 vs. 17.13 ng/ml &plusmn; 4.25; p=0.001), such as patients with proximal deep vein thrombosis (19.37 ng/ml &plusmn; 5.33 vs. 17.13 ng/ml &plusmn; 4.25; p=0.013). The same was obtained when compared patients with provoked venous thrombosis and controls (19.93 ng/ml &plusmn; 3.97 vs. 17.13 ng/ml &plusmn; 4.25; p=0.000), and patients with unprovoked venous thrombosis and controls (19.53 ng/ml &plusmn; 5.97 vs. 17.13 ng/ml &plusmn; 4.25; p=0.023). As far as genetic analysis, in the group of patients we had 25% homozygous and 58% heterozygous carriers of PAI-1 gene mutation, whereas 17% of patients did&#39;t have this mutation. In controls, we had 30% homozygous and 56% heterozygous carriers of mutation and 14% of those without mutation. There was no significant difference in the frequency of 4G/4G genotype between patients with different localization of venous thrombotic process (distal DVT 29% vs. proximal DVT 21% vs. rare localization DVT 12%, p = 0.501), as well as the representation of this genotype in provoked and unprovoked deep vein thrombosis (27% vs. 23%, p = 0.642), or in isolated deep vein thrombosis compared to pulmonary thromboembolism (25% vs. 33%, p = 0.735). Finaly, our results show that suppressed fibrinolytic functionality threefold increases risk of venous thrombosis (OR 3.02, CI 1.26-7.22), elevated levels of PAI-1 have no effect on the risk of deep vein thrombosis, as evidenced by OR of 0.86 with CI 0.59-1.25, elevated levels of t-PA antigen do not affect the risk of deep venous thrombosis (OR 1.53; CI 0.79-2.94), but increased concentration of TAFI increases more than twice this risk (OR 2.25; CI 1.16-4.35). PAI-1 4G/4G genotype does not affect venous thrombotic risk (OR 0.57; CI 0.27-1.20). Based on these results, we conclude that patients with deep vein thrombosis have suppressed fibrinolytic mechanism functionality compared to healthy subjects, the levels of t-PA antigen and plasminogen are significantly higher in patients with provoked venous thrombosis than in healthy subjects, there is no difference in PAI-1 concentration in patients with venous thrombosis and healthy persons, but the patients with deep vein thrombosis, regardless of its localisation or the type have a significantly higher level of TAFI as compared with healthy subjects. In addition, we can conclude that there is no difference in the prevalence of 4G/5G polymorphism in patients with venous thrombosis and healthy persons. Finally, we can say that suppressed fibrinolytic mechanism functionality threefold increases risk of deep vein thrombosis, elevated level of TAFI-a double increases this risk, while PAI-1 4G/5G polymorphism has no influence on the risk of venous thromboembolism.</p>