Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy.

With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses.

Estradiol-mediated regulation of hepatic iNOS in obese rats: Impact of Src, ERK1/2, AMPKα, and miR-221.

PURPOSE: This study aimed to investigate in vivo effects of estradiol on the regulation of hepatic inducible nitric oxide synthase (iNOS) expression in the high fat (HF) diet-induced obesity. Also, we aimed to investigate whether activation of the extracellular signal-regulated kinase (ERK1/2), adenosine monophosphate-activated protein kinase (AMPK), Src kinase, and miR-221 is involved in estradiol-mediated regulation of iNOS in the liver of obese male Wistar rats. Male Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. Half of HF rats were treated with estradiol intraperitoneally (40 µg/kg), whereas the other half were placebo-treated 24 H before euthanasia. Results show that estradiol treatment of HF rats decreased hepatic iNOS mRNA (P < 0.05) and protein expression (P < 0.01), the protein levels of p65 subunit of nuclear factor κB (P < 0.05) and ERα (P < 0.05), ERK1/2 phosphorylation (P < 0.001), and ERα/Src kinase association (P < 0.05). By contrast, hepatic Src protein level (P < 0.05), AMPKα phosphorylation (P < 0.05), and miR-221 expression (P < 0.05) were increased in HF rats after estradiol treatment. Our results indicate that estradiol in vivo regulates hepatic iNOS expression in obese rats via molecular mechanisms involving ERK1/2, AMPK, Src, and miR-221 signaling.

A preliminary evaluation of influence of body mass index on in vitro fertilization outcome in non-obese endometriosis patients.

BACKGROUND/AIMS: Obese and overweight women experience a lower probability for pregnancy after IVF. However, despite the increasing prevalence of obesity, the large majority of infertile women are non-obese. One of the most common indications for IVF is endometriosis. Thought-provoking inverse correlation has been established between BMI and endometriosis. Lower BMI is a risk factor for development of endometriosis and a predictive factor for severe endometriosis. Since severe endometriosis carries lower reproductive chances, even after IVF, we preliminary tested a hypothesis that higher BMI among non-obese endometriosis patients improves IVF outcomes. METHODS: Preliminary retrospective observational cross-sectional study was performed in women with endometriosis as a sole infertility cause who underwent IVF. During analyzed period we performed 2782 IVF procedures. In order to achieve highly homogenous study sample and to eliminate almost all confound factors that could lead to bias, we implemented strict study criteria. The number of eligible subjects was 156 and they were divided into underweight, normal weight and overweight groups. Primary outcomes were number of retrieved oocytes, good quality oocytes, embryos, and the rates of biochemical, clinical and ongoing pregnancies. For group comparisons, we used parametric test, analysis of variance, and non-parametric tests (Kruskal-Wallis test, Chi-square test). Logistic regression and General linear model was used to assess correlation between BMI and dependent variables (outcome and stimulation duration) when adjusted for age. RESULTS: Endometriosis as a single infertility factor among IVF couples had prevalence of 5.61%. Underweight women accounted for 10.26%, normal weight 71.15% and overweight 18.59% of study population. Significant differences were not found in number of retrieved oocytes (p = 0.880), good quality oocytes (p = 0.476), obtained embryos (p = 0.706), and biochemical (p = 0.298), clinical (p = 0.770) and ongoing (p = 0.822) pregnancy rates between study groups. CONCLUSION: Although preliminary results do not support our hypothesis, increase in BMI did not adversely affect the outcome of IVF in non-obese endometriosis patients, which is in contrast to literature data as regards general population of infertile women undergoing IVF. Prospective studies with large number of patients with endometriosis or prospective case-control studies should address these issues and provide more comprehensive counseling of infertile endometriosis patients regarding achievement of optimal BMI prior to IVF with the intention of achievement higher pregnancy rates.

Cross-cultural adaptation and validation of the Serbian version of the ICS SF male questionnaire.

INTRODUCTION: The objective of this study was to cross-culturally adapt and validate ICS male SF questionnaire to Serbian language. MATERIALS AND METHODS: This study included 91 male patients with lower urinary tract symptoms and 24 men with similar age and with confirmed absence of LUTS. ICS male SF questionnaire was translated from English to Serbian language and then back-translated to English. RESULTS: Internal consistency was high in both dimensions, voiding (Cronbach's alpha = 0.916) and incontinence (Cronbach's alpha = 0.763). Comparison of the average scores between patients and controls revealed significant differences in both dimensions: voiding (med = 8 versus med = 0; P < 0.001) and incontinence (med = 3 versus med = 0; P < 0.001). Interclass correlation revealed high testretest validity in both dimensions, voiding ICC = 0.992 (P < 0.001) and incontinece ICC = 0.989 (P < 0.001). Correlation analysis revealed high agreement between ICS male SF voiding dimension and IPSS questionnaire (ρ = 0.943; P < 0.001). CONCLUSION: The Serbian version of male ICS SF questionnaire showed acceptable reliability and validity. The ICS male SF questionnaire could be used in routine practice as an easy and comprehensive tool for assessment of LUTS.

Nuclear entropy, angular second moment, variance and texture correlation of thymus cortical and medullar lymphocytes: grey level co-occurrence matrix analysis.

Grey level co-occurrence matrix analysis (GLCM) is a well-known mathematical method for quantification of cell and tissue textural properties, such as homogeneity, complexity and level of disorder. Recently, it was demonstrated that this method is capable of evaluating fine structural changes in nuclear structure that otherwise are undetectable during standard microscopy analysis. In this article, we present the results indicating that entropy, angular second moment, variance, and texture correlation of lymphocyte nuclear structure determined by GLCM method are different in thymus cortex when compared to medulla. A total of 300 thymus lymphocyte nuclei from 10 one-month-old mice were analyzed: 150 nuclei from cortex and 150 nuclei from medullar regions of thymus. Nuclear GLCM analysis was carried out using National Institutes of Health ImageJ software. For each nucleus, entropy, angular second moment, variance and texture correlation were determined. Cortical lymphocytes had significantly higher chromatin angular second moment (p < 0.001) and texture correlation (p < 0.05) compared to medullar lymphocytes. Nuclear GLCM entropy and variance of cortical lymphocytes were on the other hand significantly lower than in medullar lymphocytes (p < 0.001). These results suggest that GLCM as a method might have a certain potential in detecting discrete changes in nuclear structure associated with lymphocyte migration and maturation in thymus.

Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carcinoma.

OBJECTIVE: This study was aimed at analyzing alterations in K-ras gene and SMAD4 gene promoter in endometrial carcinoma tissue in Serbian patients. METHODS/MATERIALS: The study has encompassed 36 patients whose endometrial cancer tissue samples and peripheral blood samples were analyzed for the presence of alterations in the K-ras gene and the SMAD4 gene promoter. The detection of K-ras codon 12 mutation was performed by polymerase chain reaction restriction fragment length polymorphism technique. Analysis of mononucleotide repeat variants at -462T(15) and -4T(12) of the SMAD4 gene promoter was performed by capillary electrophoresis analysis of DNA fragments fluorescently labeled by polymerase chain reaction. RESULTS: Mutation in codon 12 of the K-ras gene was detected with relatively high frequency of 75.0% (27 of 36 cases). Analysis of 2 mononucleotide repeats in the SMAD4 gene promoter showed that in most cases, haplotypes -462T(15)/-4T(12) and -462T(16)/-4T(12) were present; whereas in one case, a novel haplotype -462T(15)/-4T(10) was detected. CONCLUSIONS: Findings on the role and potential significance of the K-ras codon 12 mutation and SMAD4 gene promoter variants in patients with endometrial carcinoma remain controversial, and their occurrence in this type of cancer should be further investigated.

Levels of non-essential trace metals and their impact on placental health: a review.

According to recent research, even low levels of environmental chemicals, particularly heavy metals, can considerably disrupt placental homeostasis. This review aims to explore the profile of non-essential trace metals in placental tissues across the globe and to specify trace metal(s) that can be candidates for impaired placental health. Accordingly, we conducted an extensive survey on relevant databases of peer-reviewed papers published in the last two decades. Among a considerable number of non-essential trace metals, arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg) were identified as the most detrimental to placental health. Comparative analysis showed remarkable differences in placental levels of these trace metals worldwide. Based on current data reported across the globe, a median (min-max) range from 0.55 to 15 ng/g for placental As levels could be deemed safe. The placental Cd and Pb levels were markedly higher in smokers than in non-smokers. Occupationally exposed pregnant women had several orders of magnitude higher Cd, Pb, and Hg levels in placental tissues than non-occupationally exposed women. Also, we concluded that even low-level exposure to As, Cd, Pb, and Hg could be deleterious to proper fetal development. This review implies the need to reduce exposure to non-essential trace metals to preserve placental health and prevent numerous poor pregnancy outcomes. Overall, the information presented is expected to help plan future fundamental and applied investigations on the placental toxicity of As, Cd, Pb, and Hg.

Elemental profiling of human semen with confirmed normozoospermia: Baseline levels for 44 elements.

BACKGROUND: As a consequence of the progressive decline in human semen quality in recent decades, modern epidemiological investigations have identified several trace elements that could be responsible for this phenomenon. However, their levels in semen have not been clearly elucidated, particularly for elements present in ultra-trace levels. METHODS: We aimed to determine the levels of 39 (ultra)trace elements and 5 macroelements in human semen samples with confirmed normozoospermia using ICP-based techniques. The research was amplified by analyzing blood samples from the same participants. RESULTS: Among the analyzed (ultra)trace elements in semen samples, Zn is the most and Tm is the least prominent. Zn levels in semen are so high that Zn should be considered as a macroelement in this matrix. The levels of Zn, Rh, Sm, Re, Ir, Tl, Na, and Ca were significantly higher in semen, while the levels of Cu, As, Rb, Gd, Sb, Tb, Tm, Lu, K, and Fe were significantly higher in blood. Correlation analysis of the levels of 44 individual elements in paired semen and blood samples revealed positive correlations between 43 of the elements, particularly for Tl and Pt. An exception was the negative correlation for Cu, which showed that its high level in semen is associated with a low level in blood and contrariwise. CONCLUSION: The reported data can be used as baseline levels/reference values for 44 elements in human semen. Furthermore, the findings of this study could be relevant for further consideration of male infertility.

Analysis of essential, toxic, rare earth, and noble elements in maternal and umbilical cord blood.

Progressive industrialization in recent decades has contributed to the increase of metal levels in the environment, which has a dangerous impact on human health, primarily pregnant women. In this study, we aimed to compare levels of various elements in maternal and umbilical cord (UC) plasma samples collected from 125 healthy pregnant women, conduct correlation analysis among paired plasma samples, and compare our data with other populations worldwide. The study design included the following elements: essential (Mn, Co, Cu, Zn, Se, Mo), non-essential (Be, Al, Ni, As, Rb, Sr, Cd, Sb, Pb, U), rare earth (La, Pr, Ce, Nd, Sm, Eu, Gd, Dy, Ho, Er), and noble metals (Ru, Rh, Re, Pt). Levels of 30 elements were higher in maternal plasma than in UC plasma samples. However, no disparities at the statistically significant level were found for Be, Zn, Rb, Cd, Ce, and Ho. Correlation analysis among paired plasma samples revealed only positive/synergistic correlations of different strengths between most elements. Compared to other countries across the globe, our participants had considerably lower plasma levels of Zn and higher levels of Co, Ni, and As. This study provides not only a new and deeper comprehension, but also the first insight into the levels, correlation, distribution, and potential transplacental transfer of 30 elements.

Combined hereditary thrombophilias are responsible for poor placental vascularization development and low molecular weight heparins (LMWH) prevent adverse pregnancy outcomes in these patients.

BACKGROUND: Even though thrombophilias are associated with negative pregnancy outcomes (PO), there is not a consensus of when thrombophilias should be screened for, or how they affect placental vascularization during pregnancy. Therefore, the main aim of this study was to discover inherited thrombophilias (IHT) in the first trimester in women with otherwise no indications for thrombophilia screening, based on their vascularization parameters. LMWH treatment in improvement of placental vascularization and PO was also assessed. Finally, the classification of thrombophilias based on observed obstetric risks was proposed. METHODS: Women were included in study based on their poor gestational sac and later utero-placental juncture vascularization signal and screening for inherited thrombophilias. LMWH were then initiated and Resistance index of Uterine artery (RIAU) was followed alongside PO (preterm birth, preeclampsia, placental abruption, intrauterine growth reduction). Study group consisted of women with combined inherited thrombophilias. Control group consisted of patients with inherited thrombophilias who have received LMWH therapy since pregnancy beginning. FINDINGS: Out of 219 women, 93 had IHT, and 43 had combined IHT. All pregnancies both in both groups ended up with live births. Vaginal birth was more present in the control group (p < .001), and all women in study group delivered by CS. Premature birth was present in 8.4% of patients in control group, and in 32.55% of the patients in the study (p < .001). PE wasn't noted, and only 1 case of PA in control group. In the control group, 6.5% patients had IUGR, and 32.55% in the study group (p < .05). Based on RIAU and PO, thrombophilia categories were established: S (severe), MO (moderate), MI (mild) and L (low). Higher risk thrombophilias had higher RIAU later in the pregnancy, earlier pregnancy termination and Intrauterine Growth Reduction (IUGR). CONCLUSIONS: Thrombophilias should be considered and screened when poor vascularization is noted early in the pregnancy with Doppler sonography. Intervention with LMWH prevents adverse PO in these patients.

Maternal and Fetal Outcomes among Pregnant Women with Diabetes.

The aim of this study was to examine the differences in pregnancy complications, delivery characteristics, and neonatal outcomes between women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This study included all pregnant women with diabetes in pregnancy in Belgrade, Serbia, between 2010 and 2020. The total sample consisted of 6737 patients. In total, 1318 (19.6%) patients had T1DM, 138 (2.0%) had T2DM, and 5281 patients (78.4%) had GDM. Multivariate logistic regression with the type of diabetes as an outcome variable showed that patients with T1DM had a lower likelihood of vaginal delivery (OR: 0.73, 95% CI: 0.64-0.83), gestational hypertension (OR: 0.47, 95% CI: 0.36-0.62), higher likelihood of chronic hypertension (OR: 1.88, 95% CI: 1.55-2.29),and a higher likelihood ofgestational age at delivery before 37 weeks (OR: 1.38, 95% CI: 1.18-1.63) compared to women with GDM. Multivariate logistic regression showed that patients with T2DM had a lower likelihood ofgestational hypertension compared to women with GDM (OR: 0.37, 95% CI: 0.15-0.92).Our results indicate that the highest percentage of diabetes in pregnancy is GDM, and the existence of differences in pregnancy complications, childbirth characteristics, and neonatal outcomes are predominantly between women with GDM and women with T1DM.

Human biomonitoring of essential, nonessential, rare earth, and noble elements in placental tissues.

Exposure to certain metals has been recognized as a risk factor for numerous complications in vulnerable population groups, particularly pregnant women. This investigation evaluated the levels of essential (Cr, Mn, Co, Cu, Zn, Se, Mo) and nonessential trace metals with recognized toxicity (Be, Al, Ti, V, Ni, Ga, As, Rb, Sr, Cd, Sb, Ba, Tl, Hg, Pb, Bi, Th, U), together with rare earth elements (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu), and noble metals (Ru, Rh, Pd, Re, Os, Ir, Pt, Au, Ag) in the placental tissues of healthy pregnant women (n = 105). The selection of participants was undertaken with special reference to specific confounding factors that could influence the trace element profiles. Among trace elements, Zn was the most abundant and Lu was the least abundant. Cd and Os placental levels show a tendency to increase with women's age. Compared with literature data, high levels of Ni were found. This is the first study that provides the composition levels of essential and toxic trace elements, rare earth elements, and noble metals in human placental tissues. Also, for the first time, normal (reference) ranges for 50 (ultra)trace elements in placental tissues are proposed. Reference ranges are especially important in biomonitoring studies, which nowadays give increasing importance to the analysis of solid tissues instead of body fluids. Overall, the information provided in this study can serve as a starting point for further clinical trials and/or prediction of potential risks to pregnancy.

Follicular and serum levels of vitamin D in women with unexplained infertility and their relationship with in vitro fertilization outcome: an observational pilot study.

INTRODUCTION: Follicular and serum vitamin D are considered potential markers of the oocyte and embryos' quality and predictors of in vitro fertilization (IVF) outcomes. METHODS: This retrospective cross-sectional study correlated vitamin D in sera and follicular fluid of women with unexplained infertility mutually and with IVF outcomes. ELISA was used for measuring vitamin D. RESULTS: The results show positive correlation only between follicular and serum levels of vitamin D (Rho = 0.615, p = 0.025), and between follicular levels of vitamin D and the percentage of embryo fragmentation (Rho = 0.544; p = 0.036). CONCLUSIONS: The results suggest that serum and follicular fluid vitamin D measurements could be complementary tools to the routine assessment of embryos.

Perinatal complications related to inherited thrombophilia: review of evidence in different regions of the world.

The term thrombophilia describes disorders associated with an increased predisposition of developing venous thromboembolism (VTE). It may be acquired, like in those with antiphospholipid syndrome or inherited. The aim of this review was to compare the complications and outcomes of pregnancies in women with inherited thrombophilia between different populations, including the population of our country where the results of the research are scarce. The review of literature included all papers indexed on PubMed and Medline in the last 20 years, with different study design, including other reviews of literature, systematic reviews with meta-analysis and several case-control studies and population-based cohort studies. We aimed to cover as many geographic regions as possible with the aim to show the differences in the different parts of the world and including our country. Our analysis showed that types of thrombophilia differ in different geographic regions. Also, the differences exist between one particular type of thrombophilia in different regions. Nevertheless, no matter what the differences are between prevalence, all authors investigated the association between inherited thrombophilia and poor pregnancy outcome and managed to find some kind of association. The case with our own country is similar. Although we lack in studies with this issue and the design of published studies is not powerful enough, we may conclude that in our samples, women with thrombophilia are in potential risk of several poor pregnancy outcomes. Further and better analyses are necessary to prove this hypothesis not only on the level of study sample but also on general population. Given the fact that thrombophilia certainly affects the pregnancy and its outcome, the urge to perform screening tests in every woman suspected to have this kind of disorder and with respect to differences that exist in different world regions is inevitable.

Distribution of normal and pathological OGTTs among pregnant population and non-pregnant women with PCOS - the cross-sectional study.

ABSTRACT: Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition.We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B.The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P < .001) for abnormal OGTT results in pregnant women compared to non-pregnant women with PCOS.We might conclude that pregnancy could have a more challenging influence on glucose metabolism and that carries higher risks for abnormal glucose metabolism than PCOS. The awareness of obstetricians regarding physiological changes during pregnancy that predisposes abnormal glucose metabolism is decreasing over time and the compliance concerning OGTT testing of pregnant women is decreasing too.

Hamilton anxiety scale (HAMA) in infertile women with endometriosis and its correlation with magnesium levels in peritoneal fluid.

BACKGROUND: Endometriosis is a complex disease that can result in substantial morbidity, including chronic pain, dysmenorrhea and dyspareunia. There are contradictory reports regarding the connection between acute and chronic stress and magnesium levels in body fluids. SUBJECTS AND METHODS: A prospective study included 87 patients undergoing laparoscopy. The study group included 40 women with endometriosis and the control group consisted of 47 women with other causes of infertility. The levels of fright were determined using HAMA scale. The measurements of Mg levels were performed using biochemical analyzer "Monarch Plus". RESULTS: One day before the operation, HAMA score was 9.54+/-7.34 in the women with endometriosis, and 6.69+/-5.51 in the women without endometriosis. The morning before the operation, HAMA score was 8.64 +/- 8.10 in the women with endometriosis, and 4.29+/-2.29 in the women without endometriosis. The second postoperative day, HAMA score was 8.96+/-7.60 in the women with endometriosis and 6.92+/-5.16 in the women without endometriosis. Higher HAMA score in the women with endometriosis, in comparison with the control group, in all three time periods has been found, but the differences were not statistically significant (p>0.05). A negative correlation between the concentration of Mg in peritoneal fluid and HAMA score was found in the control group (p<0.01). CONCLUSIONS: In infertile women without endometriosis a correlation between Mg concentration in peritoneal fluid and HAMA score was found. No such correlation was found in the women with endometriosis, possibly due to a systemic disorder in endometriosis that might affect Mg transport through the cell membrane.

Comparison of 2 approaches in management of pregnant women with inherited trombophilias: Prospective analytical cohort study.

Previous adverse pregnancy outcomes (APO) in women with hereditary thrombophilia have emerged as new indications for prophylactic use of low-molecular-weight heparin (LMWH) during pregnancy. Recent meta-analysis conducted to establish if LMWH may prevent recurrent placenta-mediated pregnancy complications point to important therapeutic effect but these findings are absolutely not universal. Furthermore, previous studies regarding LMWH prophylaxis for APO in women with inherited thrombophilia were performed in high risk patients with previous adverse health outcomes in medical, family and/or obstetric history. Therefore, the aim of this study was to investigate the effects of LMWH prophylaxis on pregnancy outcomes in women with inherited thrombophilias regardless of the presence of previous adverse health outcomes in medical, family, and obstetric history.Prospective analytical cohort study included all referred women with inherited thrombophilia between 11 and 15 weeks of gestation and followed-up to delivery. Patients were allocated in group with LWMH prophylaxis (study group) and control group without LWMH prophylaxis. The groups were compared for laboratory parameters and Doppler flows of umbilical artery at 28 to 30th, 32nd to 34th and 36th to 38th gestational weeks (gw), and for obstetric and perinatal outcomes.The study group included 221 women and control group included 137 women. Mean resistance index of the umbilical artery Ri in 28 to 30, 32 to 34, and 36 to 38 gw were significantly higher in the control group compared to study group (0.71 ±â€Š0.02 vs 0.69 ±â€Š0.02; 0.67 ±â€Š0.03 vs 0.64 ±â€Š0.02; and 0.67 ±â€Š0.05 vs 0.54 ±â€Š0.08, respectively). Intrauterine fetal death (IUFD) and miscarriages were statistically significantly more frequent in control group compared to the patients in study (P < .001). The frequencies of fetal growth restriction (FGR) and APO were significantly higher in the control group compared to the study group (P = .008 and P < .001, respectively). In a multivariate regression model with APO as a dependent variable, only Ri was detected as a significant protective factor for APO, after adjusting for age and LMWH prophylaxis (P < .001).We have demonstrated better perinatal outcomes in women with LMWH prophylaxis for APO compared to untreated women.

Hypothesis regarding the effects of gonadotropins on the level of free fatty acids and phospholipids in serum and follicular fluid during controlled ovarian stimulation.

Controlled ovarian stimulation (COS) is used to augment the number of retrieved oocytes in in vitro fertilization (IVF). Follicular fluid (FF) contributes significantly to oocyte quality. Since the FF is composed of follicular secretions and plasma exudation, it reflects alterations in granulosa and thecal cells secretion as well as changes in the level of plasma constituents. Phospholipids (PL) and free fatty acids (FFA) are important constituents of both, FF and serum. Our hypothesis is that COS affects the level of PL and FFA in serum. Furthermore, since the level of PL and FFA in FF partially depends on their levels in serum, as a collaterally of our hypothesis is that the existing level of PL and FFA in serum correlates with the levels of PL and FFA in FF, and that the dose of applied gonadotropins during COS will correlate with the levels of PL and FFA in serum and FF. In addition, we assume that the level of PL and FFA in serum and in FF after COS will correlate with the retrieved number of GQ oocytes, one of the most important outcomes of COS. .

PCSK9 and Hypercholesterolemia: Therapeutic Approach.

Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of mortality and disability in the modern world. A significant contribution to the treatment of hypercholesterolemia was made by the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is responsible for the degradation of the low-density lipoprotein (LDL) receptor (LDLR) found at the surface of the plasma membrane in the liver and directly associated with serum LDL level. Limitations in standard therapy used in the treatment of lipid disorders have led to the development of new drugs, such as an inhibitor of PCSK9. Over the past years, the greatest achievement in discovering the PCSK9 inhibitor was made by designing monoclonal antibodies that disable PCSK9 to bind LDLR and RNA interference to reduce PCSK9 production, but one of the main disadvantages is costeffectiveness. In this review, we will summarize the most recent findings of basic and clinical studies which focus on PCSK9 function, regulation and therapeutic target for the treatment of hypercholesterolemia and associated cardiovascular diseases.

Association between walking, dysphoric mood and anxiety in late pregnancy: A cross-sectional study.

Relationship between physical activity and mental disorders in late pregnancy is unclear. In this work, we demonstrate that there is a significant association between the time spent on walking and symptoms of depression and anxiety in antenatal period. The cross-sectional study was done on a sample of 200 healthy women in 9th month of physiological pregnancy at Health center Kraljevo, Serbia during 2015. Each participant was given a questionnaire consisting of general questions regarding physical activity, pregnancy, and other parameters. Also, each participant completed a Beck depression inventory (BDI) and Zung anxiety scale (ZAS). There was a statistically significant negative correlation (p<0.05) between the BDI score and the daily time spent on walking. There was also a strong positive connection between the daily time spent on walking and level of anxiety (p<0.01). To our knowledge this is the first study to jointly test the relationship between scores of Beck depression inventory and Zung anxiety scale, and time spent on walking as physical activity in antenatal period. The results represent the basis for further research in the field of gynecological psychology, psychiatry and behavioral physiology.