DOES OVARIAN AUTOIMMUNITY PLAY A ROLE IN THE PATHPHYSIOLOGY OF PREMATURE OVARIAN INSUFFICIENCY

Premature ovarian failure (POF) is a term usually used to describe women younger than 40 years of age who present with amenorrhea. Diagnosis of POF is on the basis of follicle stimulating hormone level in the menopausal range associated with amenorrhea before the age of 40. Women diagnosed with the POF suffered from anovulation and hypoestrogenism and presented with primary or secondary amenorrhea, infertility, sex steroid deficiency, and elevated gonadotrophins [1, p. 245] POF is the causative factor in 10-28% of women presenting with amenorrhea and in 4-18% with secondary amenorrhea [2, p. 236; 3, p. 45]. The course of POF is poorly defined [4, p. 112]. Perhaps 50% of spontaneously affected woman have the evidence of follicular activity and probably 25% ovulate even before the diagnosis is established. Some of these women even conceive. It is increasingly felt that it may be appropriate to refer to them as patients with «primary ovarian insufficiency.» The term primary ovarian insufficiency (POI) originally suggested by Albright appropriately describes a continuation of impaired ovarian function and is also less stigmatizing than the terms used previously [5, p. 38]. Two mechanisms are probably involved in POI, namely follicle dysfunction and follicle depletion [6, p. 253]. The existing follicles in the ovary, in follicle dysfunction, do not function normally due to some pathological process such as for e.g. FSH-receptor mutation [7, p. 86]. On the other hand, in women with follicle depletion there are no primordial follicles probably due to inadequate initial pool of primordial follicles or destruction of follicles due to toxins or autoimmune mechanisms [5, p.39]. The primary goal of the scientists working in this area should be to focus on the etiology of POI [8, p. 99] Some of the causes can lead to complete absence of oocytes, and others can lead to inability of follicles to mature or to disordered folliculogenesis. The causes could be chromosomal, genetic, autoimmune, metabolic (galactosemia), infection (mumps), and iatrogenic [9, p. 123]. Among the several mechanisms that account for the pathogenesis of spontaneous POI, genetic and autoimmune mechanisms play a major role. X-chromosome abnormalities have been systematically reviewed by Persani et al [10, p. 96]/ Normal ovarian function requires two functioning X chromosomes. In the Turner Syndrome, there is a complete loss of the second chromosome resulting in the most severe and irreversible POI often clinically evident prior to menarche [11, p. 176]. Prevalence of other genetic defects causing POI has been difficult to determine. Gene for blepharophimosis/ ptosis/POI syndrome has been recently reported but has not been seen commonly in patients with POI. Of the various knock out mice models created with deficient ovarian function, the most interesting one is a heterozygous FSH receptor knock out mouse, which has exhibited a reduced follicle reserve and early ovarian depletion [11, p.29]. In this review, we will focus on the role of autoimmunity in the pathophysiology of POI. The human ovary can be a target for an autoimmune attack under various circumstances. Clinically, the ensuing ovarian dysfunction often results in premature ovarian insufficiency characterized by amenorrhea lasting 4-6 months and is classically defined as secondary amenorrhea accompanied by a hypergonadotropic-hypoestrogenic condition before the age of 40 years [12, p. 49]. It has long been recognized that POI could be associated with nearly all organ-specific and non-organ-specific autoimmune diseases, and its association with the endocrine glands such as the thyroid, pancreas, and adrenal glands has been reported [13, p. 68]. Vallotton and Forbes [14, p. 66] were the first to describe the presence of antibodies to rabbit ova cytoplasm using sera from POI patients. Autoimmune POI (AI-POI) is characterized by organ-specific targeting of the immune response accompanied by tissue destruction, which can have widespread systemic complications in severe cases. The disease affects 1% of the general population [15, p. 78]). There could be several reasons for the differences among the study results. First, study design elements, such as antibody test format and antigen preparation and criteria for study and comparison groups differ. Second, there may be several antigenic targets, and often only one may have been assessed. Moncayo et al [19, p. 58]/ developed an ELISA using microsomes from bovine corpora lutea as the antigen. Luborsky et al. [17, p. 39] developed an ELISA kit using total human ovary/ oocytes as antigen and showed that sera from 71% of women with POF in their study had antibodies either to whole ovary or to oocytes. Wheatcroft et al [20, p. 66]/ reported an incidence ranging from 24% to 60%, depending on the source of ovarian antigen. This difference was attributed to a cyclical variation in antigenic proteins. A review published in 2006 reported that autoantigens and specific autoantibodies for the diagnosis of autoimmune POF remain to be determined [23, p. 245]. Antibodies to several potential ovarian antigens were proposed as markers of ovarian autoimmunity. They were LH receptor, [24, p. 58] FSH receptor [25, p. 36; 26, p. 56] zona pellucida (ZP), [27, p. 56] and several other antigens [22, p. 56]. In the context of POI, a false-positive report indicating autoimmunity as the mechanism of spontaneous POI could put young women at risk of inappropriate therapy, with serious consequences such as development of osteonecrosis due to glucocorticoid therapy [33, p. 48]. As the clinicians' diagnosis will be based exclusively and extensively on the detection of the presence or absence of ovarian antibodies, it is crucial that the diagnosis is a foolproof. An early and specific diagnosis of POI (especially AI-POI) is now possible with the test developed by us [30, p. 49]. This will be extremely useful for diagnosis as well as therapy for these women. The test enabled specific detection of antiovarian antibodies (AOAs) along with the identification of different molecular and cellular antigenic targets in the ovary [16, p.56]. This is important because [1, p. 133] it will help identify antigenic targets that will lead to the development of reagents to screen for AOAs that could serve as an analytical tool to detect the disease and consequently design a drug regimen for treatment [2, p. 49]. Results from laboratory clearly showed that there are specific AOAs in the sera of patients with POF. In patients who had failed at IVF-ET, AOA positivity as detected by western blotting and immunohistochemistry (IHC), could be involved in POI [29, p. 29]. Reactivity of AOAs to ovarian cell types has been shown by indirect immu-noflourescence (IIF) [19, p. 44]. Reactivity of POF patient sera with ZP has been reported [27, p. 63; 11, p. 187]. It was suggested that Zp could be an important ovarian antigen. However, our data clearly indicated that, besides ZP, several proteins from other cellular targets such as oocytes, corpus luteum, theca, and granulosa cells are also involved in ovarian autoimmunity, and therefore, there cannot be a diagnostic test on the basis of one single biomarker [28, p. 68]. It is possible that inpatients showing reactivity to oocytes and granulosa cells the antibodies may damage the bidirectional communication which is necessary for proper folliculogenesis as reported recently. [21, p. 94]. A specific noninvasive test is particularly important for a reliable diagnosis of an autoimmune etiology and is essential to detect concomitant or future associated disorders, as well as to select the patients in whom immune-modulating therapy may restore, at least temporarily, ovarian function and fertility. Glucocorticoid therapy has been suggested to restore ovarian function [13, p. 66]. A prospective, randomized controlled study of alternate prednisone therapy for AI-POF was taken up at clinical center of the National Institutes of Health. However, lack of a noninvasive diagnostic serum marker necessitated histological confirmation of the disease using biopsy before prednisone administration. Repeated IVF attempts are likely to induce production of AOAs because of repeated hormonal stimulation [19, p. 45] and repeated microtrauma during oocyte retrieval [24, p. 88]. It has been shown by these researchers that these antibodies could affect egg development and embryo development and could be responsible for implantation failures. There are the reports showing higher prevalence of these antibodies in patients with IVF failures than those with IVF success [25, p. 87]. It has also been stressed that follicular aspiration may not be the cause for antiovarian autoimmunization [26, p. 69]. Moreover, in some cases, AOAs appear after follicular aspiration, whereas in other cases, preexisting AOA levels increase with the number of IVF attempts [27, p. 69] Therefore, testing for the presence of AOAs in women before initiation into the IVF-ET program should be recommended because this would help to counsel the patients regarding the reproductive outcome with iVf. We also propose that the AOA test should be a part of the battery of tests included for infertility treatment and management. Very little is known about the precise nature of the ovarian antigens that are recognized by the antibodies in sera. Antigens of oocyte, [14, p. 238] corpus luteum, [17, p. 69] granulosa cells, [16, p. 128] and ZP [21,p. 62] have been reported to act as autoantigens; however, their molecular identity and pathophysiologic significance remain obscure. The oocyte seems to be the most often targeted cell of AOA detected in cases of ovarian diseases as well as in women with poor assisted reproductive technologies (ART) outcomes [22, p. 89]. A thorough literature review on infertility with autoimmune involvement has indicated that very few proteins have been formally identified and characterized using sera of women with infertility [28, p. 146]. One report demonstrated autoantibodies to a-enolase, [30, p. 66] and several reports have shown the presence of circulating antibodies directed toward different ovarian structures [16, p. 49; 17, p. 57; 22, p. 86] Identification and systematic characterization of target antigens are the prerequisites for elucidation of the underlying immunologic mechanisms and also for devising better approaches for the diagnosis and treatment of POI leading to infertility [36, p. 89]. Once their identity has been established, they could be used for simple, noninvasive diagnostic tests to screen large populations of women with infertility or repeated implantation failures as well as to screen patients before and after enrollment in an IVF-ET program. Although a number of tests have been developed to detect these antibodies, neither their specificity nor their diagnostic relevance has been established

Řízení výkonnosti podniku v době krize

V příspěvku byly diskutovány současné nástroje pro řízení výkonnosti. Pozornost byla nejvíce zaměřena na moderní nástroje jako ekonomická přidaná hodnota a její propojení s konceptem Balanced Scorecard. V další části byly charakterizovány dopady krize na výkonnost podniku. Znalost dopadů krize byla základem pro diskuzi, zda současné či tradiční přístupy stačí na řízení výkonnosti v době krize. Tradiční finanční metody neposkytují včasné a přesné údaje nutné pro řízení výkonnosti. Pro úspěšné řízení výkonnosti v období krize je nutné využívat více nástrojů, které budou schopny reagovat na dopady krize. Zejména lze doporučit využití nástrojů jako je EVA+BSC, kalkulace nákladů pomocí ABC a řízení rizik.In this article the present tools for performance management were discussed. The focus was aimed on modern tools such as economic value added and its link to concept Balanced Scorecard. In the next part the impacts of crisis on company performance were charterized. The knowledge of impacts of crisis was essential for the discussion whether the current or traditional tools suit in a period of crisis. The traditional financial methods don’t provide timely and accurate information, which is necessary for performance management. In a period of crisis it is necessary to use for success more tools, which will be able to respond on impacts of crisis. Particularly it is possible to use such tools as EVA+BSC, as calculating the costs with ABC and as risk management

Izazovi izbegličke krize u Srbiji

U radu su razmatrani ekonomski i pravni aspekti izbegličke krize nastale zbog rata u Siriji. Cilj rada jeste da pokaže kompleksnost problema izbegličke krize na teritoriji Republike Srbije. Početak istraživanja obuhvata analizu izbegličke krize u Srbiji koja se odnosi na broj izbeglica koji su izrazili nameru da traže azil i strukturu izbeglica prema zemlji porekla. Nakon toga, procenjen je deo direktnih troškova države kao i ukupna potrošnja izbeglica pri prolasku kroz Srbiju u 2015. godini. Identifikovani su troškovi koji se nalaze u operativnom planu Vlade Republike Srbije, troškovi prihvatnih i azilantskih centara, kao i izvori finansiranja direktnih troškova. Dodatno je analiziran Zakon o azilu u svim zemljama bivše Jugoslavije i utvrđene su tačke konvergencije i divergencije u ovim zakonima

GLOBALNA KRIZA, OPORAVAK I SVIJET KOJI SE MIJENJA

The global economic crisis that lasted mostly during the years 2008 and 2009 has been the worst since the Great depression. Although statisti-cally the crisis seems to be over in most regions, the way to recovery rea-ching the pre-crisis levels will be long, painful and uncertain. It has to be pointed out that in some countries around the globe not even by the year 2010 the crisis was not over. On the overall the rebound had been weak and globally uneven. There seems to be under way a strong shift of economic activities towards Asian countries. This is more than evident in the case of China and India. In order to evaluate the process of global development well, an under-standing of this process prior to the crisis, the sources of the crisis, the effects of the crisis and the recovery path should be analyzed. In this paper the focus is on some of those issues.In the fi rst chapter of the paper the global situation prior to the crisis and the effects of the crisis since its outbreak are examined. The scope are the main regions of the world and signifi cant countries underlining the dif-ferences in development approaches, main factors of growth and the broad levels of global linkages facing them. The following chapter focuses on the aspects and implicit polarization outcomes. In a world in which inequalities of income distribution and poverty are as it seems on the rise and have been aggravated by the crisis, invite for the reexamination of the basic theories at hand. This is being presented it the third chapter. The theories and espe-cially the neo-liberal approach are being confronted by the facts offered by economic reality. The concluding remarks of the last chapter of the paper provide further questions on global federalism, the constraints and possibi-lities under the implicit assumption that they might develop without drastic confrontations and radical nationalistic outbursts.Globalna ekonomska kriza koja je bila očitija tijekom godine 2008. i godine 2009. bila je najteža od Velike svjetske krize. Iako statistički izgleda da je najteže razdoblje krize prošlo, put oporavka iz krize na razine iz predkriznih vremena po svemu sudeći biti će dugotrajan, bolan i neizvjestan. Pri tome valja istaknuti da neke države svijeta nisu izašle iz krize niti u godini 2010. Promatrano u cjelini dosadašnji globalni oporavak bio je slab i neujednačen. Diferencijacija globalnog ekonomskog rasta ukazuje da se odvija snažan pomak gospodarskih aktivnosti u pravcu zemalja Azije. To je najočitije kada se promatraju države poput Kine i Indije.Da bi se donio sud o procesu globalnog razvitka, potrebno je razumjeti procese razvitka u razdoblju prije krize, utvrditi bitna izvorišta krize kao i procijeniti učinke krize te razmotriti mjere izlaska iz krize. Ovaj rad usredotočio se je na neka od ovih pitanja. U prvom se dijelu rada razmatraju prilike prije izbijanja krize kao i učinci krize po njenom izbijanju. Promatraju se glavne ekonomske regije svijeta kao i ključne države sa ciljem da se ukaže na razlike u pristupu razvitku, na glavne čimbenike rasta i bitne razine globalnih odnosa koji su uspostavljeni. U drugom poglavlju rada se razmatra pojavu globalne polarizacije i njene učinke. U svijetu u kojem dohodovne nejednakosti i siromaštvo čine konstantu, s pojavom krize i njenim posljedicama ove su se najednakosti samo pogoršale. Takvo je stanje izazov za preispitivanje prevladavajućih razvojnih teorija, o čemu se razmatra u trećem dijelu rada. U tom se dijelu neo-liberalna teorija sučeljava sa činjenicama iz ekonomske stvarnosti te se ukazuje na potrebu i načine revizije takvog pristupa. Zaključni dio razmatra neke ideje s pogledom unaprijed u kojem se traži drugačiji pristup razvojnoj teoriji kao i jasniji odnos države odnosno nacije u njenom širem okruženju. Moguće rješenje vidi se u globalnom federalizmu u svjetlu ograničenja i mogućnosti koje se mogu pojaviti na tom putu, a da se pri tom izbjegnu drastične konfrontacije i radikalne nacionalističke tendencije

Investing in real astate projects in the company PV Invest d.o.o.

The purpose of the graduation thesis is to analyze investments in real estate projects in the company PV Invest d.o.o.. Two projects were chosen for the analysis: construction of a block of flats in the Municipality of Mozirje and construction of houses in the Municipality of Velenje. For this purpose, the residential real estate market analysis for the areas mentioned was conducted. Based on a comparison of already sold real estate properties in question, their average selling price for 2013 was calculated. Our analysis results were compared to the results of the analyses of the residential real estate advertising prices in the Savinja region and in Velenje as well as to the expected price of real estate projects in question. This price was calculated on the basis of costs needed for the project implementation. According to the results, the expected prices for the projects are relatively high in comparison to the estimated market values and average selling price of residential real estate in the region in question respectively. Investors and sellers respectively should keep up to date with happening in the real estate market, and, accordingly, make decisions on investing in construction and selling residential real estate respectively

Krizno komuniciranje i odnosi s javnostima s posebnim osvrtom na preuzimanje tvrtke „Pliva“

U suvremenom svijetu, kojega karakterizira sve jača globalizacija i stalan napredak tehnologije i tržišnog gospodarstva, krize su postale uobičajeni dio svakodnevice. Ukoliko je nepripremljena, organizacija može vrlo teško primiti nastanak krize i, kao posljedicu toga, borbu za vlastito preživljavanje. S druge strane, dobro pripremljena organizacija promatra krizu kao izazov koji može potaknuti analizu postojećih poslovnih rezultata i iznalaženje načina za njihovo poboljšanje. Uprava Plive se 2006. suočila s mogućnošću da preuzimanja tvrtke. Za vrijeme nadmetanja konkurenata za kupnju Plive njezin je menadžment komunicirao s dionicima tvrtke nepravilno i netransparentno. Uz već postojeću poslovnu krizu nastala je i ona komunikacijska. Provedena analiza objava pet mrežnih izdanja hrvatskih novina pokazala je da su događaji povezani s preuzimanjem Plive percipirani negativno od strane javnosti, ponajviše radi upletenosti politike u proces kao i nedostatka informacija iz tvrtke. Plivina nepripremljenost za djelovanje u uvjetima krize dodatno je zakomplicirala situaciju

Especially vulnerable groups in EU and Serbian labor market

The paper analyzes the situation of especially vulnerable groups both in EU and in the Serbian labour market. They include Roma as particularly vulnerable ethnic minority, refugees and displaced persons from Kosovo and Metohija (IDPs) and people with disabilities. The results of the analysis indicate that the position of these groups is particularly disadvantaged since their unemployment rate in Serbia is significantly higher than among the general population. It turned out that the high unemployment and low employment activity rates are the main causes of extreme poverty among the Roma and Romani women which are particularly affected by the problem of unemployment. The population of refugees and IDPs is different than in the general population of Serbia primarily in higher participation of self-employed and lower participation of persons who share the status of unpaid family members. Unemployment rate of persons with disabilities is close to the level of average unemployment rates due to high rates of inactivity. Roma and people with disabilities belong to category of highly vulnerable population, as long as the refugees and internally displaced persons belong to moderately vulnerable population. Due to the lack of data we could have not determined a solid indicator of change in their position during the economic crisis.Labour Market, Especially Vulnerable Groups, Unemployment

Nanook News, Vol. 04, No. 30 (May 16, 1963)

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Vpliv globalne krize na zunanjetrgovinske tokove

Svetovno gospodarstvo se sooča z globalno krizo, ki se je v zadnjem četrtletju leta 2008 iz finančnega sektorja razširila v realnega. Posledično sta se zmanjšala industrijska proizvodnja ter obseg naložb, opaziti je tudi precejšen upad globalnih trgovinskih tokov. V prispevku bomo opredelili razloge za zmanjšanje obsega globalne trgovine, analizirali spremembe v obsegu trgovinskih tokov, odzive držav v smislu sprememb na področju zunanjetrgovinskih politik (tudi v primerjavi s krizama leta 1929 in leta 1970) ter dejavnosti, ki jih v povezavi z globalno krizo in zunanjo trgovino izvajajo mednarodne institucije: Svetovna trgovinska organizacija (WTO), Organizacija za ekonomsko sodelovanje in razvoj (OECD), Mednarodni denarni sklad (IMF), Svetovna banka (WB) ter Evropska komisija (EK)