Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors.

Fluorination of 13-epimeric estrones and their 17-deoxy counterparts was performed with Selectfluor as the reagent. In acetonitrile or trifluoroacetic acid (TFA), 10ß-fluoroestra-1,4-dien-3-ones were formed exclusively. Mechanistic investigations suggest that fluorinations occurred via SET in acetonitrile, but another mechanism was operative in TFA. Simultaneous application of N-chlorosuccinimide (NCS) and Selectfluor in TFA led to a 1.3:1 mixture of 10ß-fluoroestra-1,4-dien-3-one and 10ß-chloroestra-1,4-dien-3-one as the main products. The potential inhibitory action of the 10-fluoro- or 10-chloroestra-1,4-dien-3-one products on human aromatase was investigated via in vitro radiosubstrate incubation. The classical estrane conformation with trans ring anellations and a 13ß-methyl group seems to be crucial for the inhibition of the enzyme, while test compounds bearing the 13ß-methyl group exclusively displayed potent inhibitory action with submicromolar or micromolar IC50 values. Concerning molecular level explanation of biological activity or inactivity, computational simulations were performed. Docking studies reinforced that besides the well-known Met374 H-bond connection, the stereocenter in the 13 position has an important role in the binding affinity. The configuration inversion at C-13 results in weaker binding of 13α-estrone derivatives to the aromatase enzyme.

Neonates' responses to repeated exposure to a still face.

AIM: The main aims of the study were to examine whether human neonates' responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm. METHODS: The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day. RESULTS: Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase. CONCLUSION: After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern.

Pregnancy does not affect fecal calprotectin concentration in healthy women.

BACKGROUND/AIMS: Noninvasive activity markers are extremely important in conditions, such as pregnancy, when endoscopy is not recommended. The aim of this prospective study was to determine fecal calprotectin (FC) concentrations in healthy non-pregnant and pregnant women and in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: Healthy pregnant and non-pregnant women and patients with active and inactive IBD were prospectively enrolled in this study. Demographic and clinical parameters and clinical disease activity scores in patients with IBD were recorded. Blood and stool samples of every patient were obtained to determine C-reactive protein and FC levels. FC levels were measured with a quantitative lateral flow assay. RESULTS: One hundred and thirty-five subjects were enrolled in the study (24 non-pregnant and 48 pregnant healthy women, 40 non-pregnant patients with active IBD and 23 non-pregnant patients with inactive IBD). FC was significantly higher in active IBD patients than in pregnant (p<0.001) and non-pregnant healthy women (p<0.001). No difference could be detected in FC concentrations between pregnant and non-pregnant healthy women. CONCLUSION: Since FC levels remained unchanged during pregnancy, it may be a useful noninvasive diagnostic tool in pregnancy for monitoring mucosal inflammation.

Placental Volumetry by 2-D Sonography with a New Mathematical Formula: Prospective Study on the Shell of a Spherical Sector Model.

The aim of this study was to determine the utility of a new mathematical model in volumetric assessment of the placenta using 2-D ultrasound. Placental volumetry was performed in a prospective cross-sectional survey by virtual organ computer-aided analysis (VOCAL) with the help of a shell-off method in 346 uncomplicated pregnancies according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Furthermore, placental thickness, length and height were measured with the 2-D technique to estimate placental volume based on the mathematical formula for the volume of "the shell of the spherical sector." Fetal size was also assessed by 2-D sonography. The placental volumes measured by 2-D and 3-D techniques had a correlation of 0.86. In the first trimester, the correlation was 0.82, and later during pregnancy, it was 0.86. Placental volumetry using "the circle-shaped shell of the spherical sector" mathematical model with 2-D ultrasound technique may be introduced into everyday practice to screen for placental volume deviations associated with adverse pregnancy outcome.

Examination of placental three-dimensional power Doppler indices and perinatal outcome in pregnancies complicated by intrauterine growth restriction.

OBJECTIVE: To examine placental vascularization using three-dimensional power Doppler (3DPD) ultrasonography in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: The present prospective study was conducted at the University of Szeged (Szeged, Hungary) from February 2012 to March 2013. Women with a singleton pregnancy who attended the maternity outpatient ward in the second or third trimester were enrolled consecutively. Women were divided into two groups: those with a normal pregnancy and those with a pregnancy complicated by IUGR. Three 3DPD indices-vascularization index (VI), flow index (FI), and vascularization flow index (VFI)-were assessed. RESULTS: A total of 223 women were enrolled: 171 were in the control group and 52 in the IUGR group. Median VI was 3.7% (interquartile range [IQR] 3.2%-4.2%) in the IUGR group and 10.1% (IQR 8.6%-10.9%) in the control group (P=0.001). Median FI was 40.0 (IQR 39.7-42.5) in the IUGR group and 45.1 (IQR 44.1-53.1) in the control group (P=0.012). Median VFI was 2.2 (IQR 2.1-2.4) in the IUGR group and 4.8 (IQR 4.4-5.3) in the control group (P<0.001). CONCLUSION: Placental vascularization was reduced in pregnancies complicated by IUGR.

Adrenal haemorrhage in term neonates: a retrospective study from the period 2001-2013.

OBJECTIVE: To assess the incidence, risk factors and clinical presentations of neonatal adrenal haemorrhage (NAH) in uncomplicated, singleton and term deliveries. METHODS: A retrospective analysis of 26,416 term neonates delivered between 2001 and 2013, and screened with abdominal ultrasonography. RESULTS: Of the 26,416 neonates, 74 (0.28%) displayed NAH; the male/female ratio was 1.55:1. Vaginal delivery was significantly more frequent than caesarean section among them (71 versus 3; 95.9% versus 4.1%). Unilateral bleeding occurred on the right side in 36 (48.7%), and on the left in 34 (45.9%), without a significant difference; bilateral haematomas were found in four cases (5.4%). The most common risk factors were macrosomia (16, 21.6%) and fetal acidaemia (23, 31%), while four (5.4%) neonates exhibited pathological acidaemia. Clinical presentations included jaundice in 37 (50%), anaemia in six (8.1%) and an adrenal insufficiency in only one (1.3%) case. In three cases, neuroblastoma was diagnosed. CONCLUSIONS: Vaginal delivery, macrosomia and fetal acidaemia are the most important risk factors for NAH. The adrenal glands on both sides were similarly involved. In the healthy neonates with NAH, the clinical presentations were mild, with spontaneous regression. Differentiation of NAH from tumours is of considerable importance.

[Fetus, small for gestational age]. / A kis súlyú magzat.

A small for gestational age foetus is defined by the foetal weight below the 10th centile for the corresponding gestational age. However, the vast majority of these cases has no apparent underlying abnormality, while in other cases a serious causative pathological condition can be identified. The detection, follow-up and treatment of an intrauterine growth retarded, compromised foetus has great obstetric and neonatologic relevance. In this review, the causes, clinical aspects and screening methods of intrauterine growth retardation are summarized based on the most recent international guidelines. Furthermore, recommendations regarding the monitoring and the optimal timing of the labour induction of pregnancies complicated with intrauterine growth retardation are discussed.

Non-medical determinants of cesarean section in a medically dominated maternity system.

OBJECTIVE: To assess the contribution of non-medical factors to actual mode of delivery in a setting with high cesarean rates. DESIGN: Follow-up survey. SETTING: University department of obstetrics and gynecology. SAMPLE: Women with singleton pregnancies (n = 453) where there was no awareness of medical contradictions to vaginal delivery, attending for routine mid-pregnancy ultrasound examination in November 2011 to March 2012, and delivering between March and August 2012. METHODS: Structured questionnaire completed in gestational weeks 18-22. Information on subsequent delivery was obtained from patient files and through personal contact. MAIN OUTCOME MEASURES: Contribution of childbirth preference, Wijma Delivery Expectancy/Experience Questionnaire A score, socio-demographic characteristics, attitudes toward birth issues and circumstances of pregnancy/delivery to mode of delivery. RESULTS: The majority of respondents (410/453; 90.5%) preferred vaginal delivery; nevertheless, one-third (two-fifths of nulliparas) had a cesarean delivery. Among nulliparous respondents, a longer perceived interval from decision for pregnancy to conception, lower importance assigned to personal control, and the presence of an obstetrician with power to decide about cesarean delivery, were independent contributors to the binary logistic regression model explaining higher maternal cesarean risks. For parous respondents, corresponding factors were younger maternal age, perceived environmental influence towards cesarean section, the respondent's belief that cesarean is more beneficial than vaginal delivery and an older obstetrician attending the delivery. CONCLUSIONS: The results of this questionnaire survey contribute to the already existing evidence that against the background of high cesarean rates, non-medical factors, as much related to the obstetricians as to pregnant women's attitudes, play an important role.

Learning to imitate individual finger movements by the human neonate.

Imitation in human neonates, unlike imitation in young infants, is still regarded as controversial. Four studies with 203 newborns are presented to examine the imitation of index finger, two- and three-finger movements in human neonates. Results found differential imitations of all three modelled gestures, a left-handed pattern, and a rapid learning mechanism. The lateralized behavioural pattern suggests the involvement of a right lateralized neural network, and the mechanisms described in this study - (i) the accurate imitation of all aspects of the model's movements, (ii) the rapid learning component, and the (iii) the early sensitive period might fulfil the criteria for filial imprinting.

Women's antenatal preferences for delivery route in a setting with high cesarean section rates and a medically dominated maternity system.

OBJECTIVE: To assess birth preferences in a sample of Hungarian pregnant women and identify determinants of ambivalence or clear choices for cesarean section throughout pregnancy. DESIGN: Follow-up two-point questionnaire survey. SETTING: University Department of Obstetrics and Gynecology in Hungary. SAMPLE: A total of 413 women with singleton pregnancies where there was no awareness of medical contradictions to vaginal delivery, attending for routine ultrasound examination in mid-pregnancy from November 2011 to March 2012. METHODS: Questionnaires completed in mid- and late pregnancy (gestational weeks 18-22 and 35-37) including the Wijma Delivery Expectancy/Experience Questionnaire A. MAIN OUTCOME MEASURES: Prevalence of women preferring cesarean section or being uncertain about what delivery route to choose, in case they had the choice; their demographic characteristics, attitudes toward birth issues and their Wijma Delivery Expectancy/Experience Questionnaire A scores, compared with women consistent in their preference for vaginal delivery. RESULTS: Of the 413 respondents, 365 (88.4%) were consistent in their preference for vaginal delivery. In logistic regression models the important contributors to describing preferences for cesarean section or uncertain preferences were previous cesarean section and maternal belief that cesarean section is more beneficial than vaginal delivery. CONCLUSIONS: The majority of pregnant women preferred vaginal delivery to cesarean section. Neither a higher Wijma Delivery Expectancy/Experience Questionnaire A score nor sociodemographic differences were important determinants of a preference for cesarean section or for an uncertain preference. On the other hand, previous cesarean section and certain preconceived maternal attitudes towards delivery were characteristic for these women.

Identification of causes of stillbirth through autopsy and placental examination reports.

The autopsy and placental histopathological examination results following fetal deaths were analyzed retrospectively in an attempt to explain the stillbirths that occurred from 1996 to 2010 at the Department of Obstetrics and Gynecology, University of Szeged. One hundred and forty fetal deaths were recorded in that period, i.e. a rate of 4.69 stillbirths per 1000 deliveries. The postmortem examination provided the exact cause of the fetal death in 57.9% of the cases. The most common causes were a placental insufficiency (46.9%) and an umbilical cord complication (25.9%). In the first half of the third trimester, a placental insufficiency predominated as the cause of stillbirth, whereas mainly umbilical cord complications occurred around term. In spite of the availability of the autopsy and histopathological examination results, the proportion of unexplained stillbirths in our sample was relatively high. A considerable proportion of stillbirth cases could probably be prevented by more effective screening of a placental insufficiency.

[Cesarean delivery on maternal request: survey among obstetricians/gynecologists in south-east Hungary]. / Császármetszés anyai kérésre - ahogyan a délkelet-magyarországi szülész-nogyógyászok látják.

INTRODUCTION: increased frequency of maternal request for cesarean delivery may be a contributing factor to the rising cesarean section rate in Hungary, although there is no formal indication that would allow Hungarian obstetricians to perform this procedure legally. Thus, it is difficult to estimate the role of maternal request in the rising cesarean rate. AIM: The aim of the authors was to assess the attitudes of obstetricians toward this procedure. METHOD: In early 2010 anonymous questionnaires were distributed to each of the 137 obstetricians working in the maternity wards of counties Bács-Kiskun, Békés and Csongrád, with a response rate of 74.5% (n = 102). RESULTS: More than half of the respondents refused the possibility of a legalized indication for this procedure in Hungary; however, in case it was legalized, 81 (79.4%) obstetricians would feel ready to perform it. CONCLUSIONS: The resistance of more than half of the obstetricians to an explicit indication for the procedure is in conflict with the theoretical willingness of the majority of them to perform it.

The Edinburgh Postnatal Depression Scale: translation and antepartum validation for a Hungarian sample.

OBJECTIVE: the Edinburgh Postnatal Depression Scale (EPDS) is an important screening instrument routinely used during the peripartum period for the identification of depression. The purpose of the study was to assess the validity of the 10-item EPDS in screening for antepartum depression (APD) in Hungary. DESIGN: validation study carried out between July and December 2010. SETTING: Department of Obstetrics and Gynecology, University of Szeged, Hungary. PARTICIPANTS: 219 women attending a routine check-up at 12 weeks antepartum. INTERVENTIONS: participants completed the newly translated Hungarian version of the EPDS and underwent a clinical assessment with the Structured Clinical Interview for DSM-IV disorders (SCID-I). MEASUREMENT AND FINDINGS: seven (3.2%) of the mothers were diagnosed with major antepartum depression and 15 persons (6.85%) with minor depression on the basis of the SCID. Internal consistency of the EPDS was satisfactory (Cronbach α coefficients ≥0.728). The best cut-off on the Hungarian version of the EPDS for major depression was 8/9, with a sensitivity of 71.4%, and a specificity of 91.5%. The area under the ROC curve was found significant for combined depression as well and at a cut-off of 6/7 indicated a sensitivity of 81.8% and a specificity of 83.2%. KEY CONCLUSIONS: the EPDS showed acceptable validity despite a considerable scatter in the total scores in our sample. IMPLICATION FOR PRACTICE: the EPDS is a reliable instrument for the screening of depressive disorders, especially major depressive disorder in early pregnancy among Hungarian women.

Magnetic resonance vs. sonographic imaging: diagnostics of a large congenital pulmonary airway malformation.

Sonographic scan revealed a homogenously hyperechogenic lesion in the right fetal lung with microcystic pattern by a primigravid women at 22nd weeks of gestation. A large congenital pulmonary airway malformation (CPAM) was suspected with a lesion-to-lung ratio over 90%. The microcystic image of this thoracic anomaly was moderately visible on magnetic resonance imaging (MRI) at that early stage of the pregnancy. Fetopsy confirmed the diagnosis as a pure microcystic CPAM following termination of pregnancy. A controlled prospective study could be performed to compare ultrasound as a diagnostic modality to the MRI, focusing on volumetry, signal characteristics, and follow-up/regression of fetal pulmonary malformations.

Management of severe idiopathic oligohydramnios: is antepartum transabdominal amnioinfusion really a treatment option?

OBJECTIVE: The aim of this study was an evaluation of the role of antepartum transabdominal amnioinfusion (APTA) in the management of severe idiopathic oligohydramnios with a view to improving the pregnancy outcome. METHODS: The study comprised an analysis of 20 pregnant women with severe oligohydramnios who were treated with APTA in 2009 and 2012. The pregnancy outcomes and the complications of the procedure were analysed. RESULTS: The mean gestational age at first treatment was 22 weeks 3 days. The preprocedure amniotic fluid index of <5 cm was restored by the treatment to 8 cm. More than a half of the pregnancies (66.7%, 8/12) treated with APTA finished with spontaneous abortion in the second trimester, mostly due to rupture of the membranes (as a consequence of retroamniotic filling with saline in four cases). The later the oligohydramnios developed, the higher the probability of a significant prolongation of the gestation. CONCLUSIONS: Although APTA is a useful procedure in the management of severe oligohydramnios, it may be followed by a relatively high rate of rupture of the membranes, particularly in the second trimester. Paradoxically, a higher volume of infused saline into the amniotic cavity is associated with a significantly lower risk of rupture.

Predictors of oral contraceptive use among teenaged girls in southeastern Hungary.

OBJECTIVE: To assess the main determinants of oral contraceptive (OC) use among teenaged girls in southeastern Hungary. METHODS: A questionnaire was self-administered by 332 participants aged 14 to 19 years seen at the Contraception Outpatient Clinic for Teenagers located in the Department of the Obstetrics and Gynecology of the University of Szeged from May 1, 2005, to March 31, 2006. RESULTS: Approximately half of the respondents (48.2%) used OCs, and only 21.9% of the OC users considered OC cost unimportant (vs 59% of the non-OC users). A considerable proportion in each group knew little about the fertile period of a menstrual cycle (43.1% vs 46.5%) and had an insufficient knowledge of the recommendations regarding pill use (66.6% vs 77.9%). Most (76.2%) of the participants intended to use OCs in the future. Intending to use OCs was strongly associated with the prevention of menstrual disorders (adjusted odds ratio [AOR], 4.73; 95% confidence interval [CI], 2.4-10.5) and the opinion that OCs did not interfere with sex life (AOR, 2.55; 95% CI, 1.3-5.1). CONCLUSION: The results demonstrate that the knowledge of teenaged girls concerning the correct use of OCs and the differences in fertility during the menstrual cycle is often inadequate and should be improved.

Obstetric and psychosocial risk factors for depressive symptoms during pregnancy.

We aimed to determine the psychosocial and obstetric correlates of depressive symptomatology during pregnancy in South-Eastern Hungary. A total of 1719 women were screened for depression in four counties in 2006 and 2007, based on a Leverton Questionnaire (LQ) score of ≥12 at 14-24 weeks of gestation. The LQ scores indicated a probable depressive illness (PDI) in 17.2% of the study group. The best predictors in a multiple regression analysis were history of major depression (adjusted odds ratio [AOR]=3.23), and major life events (AOR=2.43). A perceived lack of social support from partner (AOR=1.79) and lack of support by family (AOR=1.23) were also significant determinants. Lack of planning of pregnancy (AOR=1.12) and a history of unfavourable obstetric outcome (AOR=1.42) also seem to predispose to PDI. Overall, psychosocial factors appeared important in the prediction of PDI, whereas economic features did not.

Determinants of emergency contraceptive use after unprotected intercourse: who seeks emergency contraception and who seeks abortion?

OBJECTIVE: To compare differences in contraceptive characteristics and the knowledge of emergency contraception (EC) between women who used EC after unprotected intercourse and those who sought abortion. DESIGN: A questionnaire survey. SETTING: A Hungarian university hospital. SAMPLE: Two large clinical groups were enrolled: women who were prescribed EC after unprotected intercourse (n= 952) (EC group) and women who presented for termination of pregnancy who had not taken EC after a contraceptive failure despite being suitable candidates to take EC (n= 577) (control group). METHODS: Questionnaire evaluation. MAIN OUTCOME MEASURES: Knowledge concerning, previous use of, and other factors related to EC use. RESULTS: The EC group experienced a condom failure significantly more often (odds ratio (OR) = 3.07), while the control group reported more failures with the contraceptive pill (OR = 0.69) and with periodic abstinence (OR = 0.09). Use of EC depended on age, education level, place of residence, accurate knowledge of EC (OR = 3.87) and previous EC use (OR = 1.16). Awareness of EC was influenced by information obtained from healthcare providers (OR = 3.63) or by school education (OR = 1.28). CONCLUSIONS: Women who use less reliable contraceptive methods should be targeted for health education that stresses the importance of reliable contraception and provides more detailed knowledge on EC and when it should be used.