Microbiome Dynamics and Functional Composition in Coelopa frigida (Diptera, Coelopidae): Insights into Trophic Specialization of Kelp Flies.

Coelopidae (Diptera), known as kelp flies, exhibit an ecological association with beached kelp and other rotting seaweeds. This unique trophic specialization necessitates significant adaptations to overcome the limitations of an algal diet. We aimed to investigate whether the flies' microbiome could be one of these adaptive mechanisms. Our analysis focused on assessing composition and diversity of adult and larval microbiota of the kelp fly Coelopa frigida. Feeding habits of the larvae of this species have been subject of numerous studies, with debates whether they directly consume kelp or primarily feed on associated bacteria. By using a 16S rRNA metabarcoding approach, we found that the larval microbiota displayed considerably less diversity than adults, heavily dominated by only four operational taxonomic units (OTUs). Phylogenetic placement recovered the most dominant OTU of the larval microbiome, which is the source of more than half of all metabarcoding sequence reads, as an undescribed genus of Orbaceae (Gammaproteobacteria). Interestingly, this OTU is barely found among the 15 most abundant taxa of the adult microbiome, where it is responsible for less than 2% of the metabarcoding sequence reads. The other three OTUs dominating the larval microbiome have been assigned as Psychrobacter (Gammaproteobacteria), Wohlfahrtiimonas (Gammaproteobacteria), and Cetobacterium (Fusobacteriota). Moreover, we also uncovered a distinct shift in the functional composition between the larval and adult stages, where our taxonomic profiling suggests a significant decrease in functional diversity in larval samples. Our study offers insights into the microbiome dynamics and functional composition of Coelopa frigida.

Self-Observation and Peer Feedback as a Faculty Development Approach for Problem-Based Learning Tutors: A Program Evaluation.

PROBLEM: Good teaching requires spontaneous, immediate, and appropriate action in response to various situations. It is even more crucial in problem-based learning (PBL) tutorials, as the tutors, while directing students toward the identification and attainment of learning objectives, must stimulate them to contribute to the process and provide them with constructive feedback. PBL tutors in medicine lack opportunities to receive feedback from their peers on their teaching strategies. Moreover, as tutorials provide little or no time to stop and think, more could be learned by reflecting on the experience than from the experience itself. We designed and evaluated a faculty development approach to developing PBL tutors that combined self-reflection and peer feedback processes, both powerful techniques for improving performance in education. INTERVENTION: We developed an observation instrument for PBL facilitation to be used both by tutors to self-observe and reflect on own teaching strategies and by peers to observe and provide feedback to tutors. Twenty PBL sessions were video-recorded. Tutors completed the instrument immediately after their PBL session and again while watching their video-recorded session (self-observation). A group of three observers completed the instrument while watching each recorded session and provided feedback to each tutor (peer observation and feedback). We investigated tutors' perceptions of the feasibility and acceptability of the approach and gathered data on its effectiveness in enhancing tutors' facilitation skills. CONTEXT: The preclinical medical curriculum at the University of Geneva is essentially taught by PBL. A new program of faculty development based on self-observation and peer feedback was offered to voluntary tutors and evaluated. OUTCOME: Our results suggest that self-observation and peer feedback, supported by an instrument, can be effective in enhancing tutors' facilitation skills. Reflection on self-observation raised teachers' awareness of the effectiveness of the strategies they used to foster student learning. This motivated a need to change their teaching practice. However, for the changes to become operative, peer feedback was required, providing the cues and strategies needed to improve the facilitation skills. LESSONS LEARNED: Peer coaching was considered feasible and useful to improve tutors' facilitation skills. Evaluating the program made it possible to assess tutors' needs and the reasons underlying their difficulties, and this in turn provided the basis for advanced workshops. Nonetheless, aspects related to logistics and the time constraints of such an individualized approach, as well as the cultural appropriation of peer coaching, might be obstacles that need to be addressed.

Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report.

BACKGROUND: The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism. CASE: A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy. CONCLUSION: The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation.

"Jack-of-all-trades" is parthenogenetic.

Sex is evolutionarily more costly than parthenogenesis, evolutionary ecologists therefore wonder why sex is much more frequent than parthenogenesis in the majority of animal lineages. Intriguingly, parthenogenetic individuals and species are as common as or even more common than sexuals in some major and putative ancient animal lineages such as oribatid mites and rotifers. Here, we analyzed oribatid mites (Acari: Oribatida) as a model group because these mites are ancient (early Paleozoic), widely distributed around the globe, and include a high number of parthenogenetic species, which often co-exist with sexual oribatid mite species. There is evidence that the reproductive mode is phylogenetically conserved in oribatid mites, which makes them an ideal model to test hypotheses on the relationship between reproductive mode and species' ecological strategies. We used oribatid mites to test the frozen niche variation hypothesis; we hypothesized that parthenogenetic oribatid mites occupy narrow specialized ecological niches. We used the geographic range of species as a proxy for specialization as specialized species typically do have narrower geographic ranges than generalistic species. After correcting for phylogenetic signal in reproductive mode and demonstrating that geographic range size has no phylogenetic signal, we found that parthenogenetic lineages have a higher probability to have broader geographic ranges than sexual species arguing against the frozen niche variation hypothesis. Rather, the results suggest that parthenogenetic oribatid mite species are more generalistic than sexual species supporting the general-purpose genotype hypothesis. The reason why parthenogenetic oribatid mite species are generalists with wide geographic range sizes might be that they are of ancient origin reflecting that they adapted to varying environmental conditions during evolutionary history. Overall, our findings indicate that parthenogenetic oribatid mite species possess a widely adapted general-purpose genotype and therefore might be viewed as "Jack-of-all-trades."

Role of decidua in trophoblastic invasion.

OBJECTIVE: Proliferation, migration and invasion of trophoblastic cells into the maternal endometrium are essential steps in human embryo implantation and placentation. Trophoblast invasion is normally limited in time, only during first and early second trimester of pregnancy, and in space, limited to the endometrium and the proximal third of myometrium. This process requires among other factors: the metalloproteinases (MMP) 2 and 9. Shallow trophoblast invasion is associated with pathologies including preeclampsia and fetal growth restriction whereas unlimited invasion is associated with hydatidiform moles and choriocarcinomas. METHODS: In order to understand the role of decidua in this endometrial invasion by trophoblastic cells, we have developed a model of coculture of decidual and cytotrophoblastic cells in which we can evaluate the effect of each partner on the proliferative and invasive properties of the other. RESULTS: Surprisingly, decidual cells secrete highest levels of MMPs, and their invasive potential seems to be increased in presence of cytotrophoblast (CTB). In contrast, invasive properties of CTB are not modified by decidual cells. CONCLUSION: CTB secrete factors that favour invasion whereas decidua seems not to play a major role in regulating CTB invasion in vitro. Moreover, it is interesting to note that decidual cells could have potent invasive capacity which could explain, at least in part, endometriosis.

Alteration of circulating Placental Leucine Aminopeptidase (P-LAP) activity in preeclampsia.

OBJECTIVE: Placental Leucine Aminopeptiadse (P-LAP) also known as oxytocinase, is secreted by syncytiotrophoblast and increases gradually during pregnancy until delivery. It is a regulator of uterine contractions, of vascular resistance and of volume of the retroplacental blood pool. Recently, it was shown that it could also regulate metalloproteinase 9 activity and thus, invasiveness of trophoblastic cells. Since development of preeclampsia could be initiated by decreased cytotrophoblastic invasion of spiral arterioles and a reduced uteroplacental perfusion, we speculate that circulating P-LAP activity could be decreased during preeclampsia. MATERIALS AND METHODS: Case-control study was evaluated in 84 women. P-LAP activity was measured in n=51 healthy pregnant women at term, and compared with n=16 normotensive women delivering preterm and n=17 women diagnosed with pre-eclampsia. P-LAP activity was determined by colorimetry in plasma samples using L-Leucine-p-nitroanilide as substrate. RESULTS: P-LAP activity was significantly lower in sera of preeclamptic women (0.91+/-0.122 mDO/min) as compared to normotensive controls (1.41+/-0.103 mDO/min; p=0.003) irrespective of time of delivery. CONCLUSIONS: These findings confirm the probable involvement of P-LAP in trophoblast invasion and development of preeclampsia.

Glucose-regulated protein 78: a new partner of p53 in trophoblast.

Although wild-type p53 protein is overexpressed in first trimester trophoblast, it is inactive towards its target genes Metalloproteinase 2 and 9. This seems to be due to a complex mechanism of inactivation and stabilization of p53 relying on the formation of protein complexes involving the N-terminus of p53. To detect the proteins associated with this sequence, we incubated biotinylated p53 N-terminal peptide in cytotrophoblastic cell medium 24 h before lysis of cells. We purified the proteins retained on biotinylated peptide using a neutravidin affinity column. Proteins were then identified by peptide mass finger printing followed or not by peptide fragmentation sequencing. Among these proteins, we identified glucose-regulated protein 78 (GRP78) and verified its interaction with p53 in trophoblastic cells by immunoprecipitation and Western blot analysis. Moreover, the decreased expression of GRP78 induced by GRP78siRNA or versipelostatin decreased the formation of high molecular weight p53 complexes and p53 monomer and increased trophoblastic invasion. These results suggest that GRP78 is involved in inactivation and stabilization of p53 and in the regulation of trophoblastic invasion.

Coculture of decidua and trophoblast to study proliferation and invasion.

Proliferation, migration, and invasion of trophoblastic cells into the maternal endometrium are essential steps of human embryo implantation and placentation. Trophoblast invasion is normally limited in time (first trimester) and space (to the endometrium and to the proximal third of myometrium). Temporal and spatial regulation of trophoblast invasion is mediated in an autocrine way by trophoblastic factors and in a paracrine way by uterine factors. Shallow trophoblast invasion is associated with pathologies including preeclampsia and fetal growth restriction whereas unlimited invasion is associated with hydatidiform moles and choriocarcinomas. In order to understand this important biological process and to characterize some of its regulatory factors, we have developed a model of coculture of decidual and cytotrophoblastic cells in which we can evaluate the effect of each partner on the proliferative and invasive properties of the other.

Hemodynamic effect of angiotensin II receptor blockade in postmenopausal women on a high-sodium diet: A double-blind, randomized, placebo-controlled study.

BACKGROUND: Hypertension becomes increasingly prevalent after menopause. Postmenopausal women are more responsive to salt than premenopausal women, and they have been reported to develop marked renal vasoconstriction on a high-sodium diet. OBJECTIVE: The aim of this study was to assess whether angiotensin II receptor blockade can restore a normal pattern of renal response to salt in postmenopausal women on a high-sodium diet. We also assessed segmental renal sodium handling in that population. METHODS: Normotensive and hypertensive postmenopausal women not receiving hormone replacement therapy were enrolled in this prospective, double-blind, placebo-controlled, crossover study. They were assigned to receive irbesartan 150 mg or placebo for 6 weeks; the sequence in which they received irbesartan or placebo was randomized. During the last week of treatment, they received a high-sodium diet (250 mmol/d). Ambulatory blood pressure (ABP), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were measured using sinistrin and para-amino-hippurate clearances. Renal sodium handling was assessed by measuring endogenous lithium clearance on day 7 of the high-salt diet. RESULTS: Nineteen women (mean age, 54.7 years; range, 43-72 years; 7 normotensive subjects [mean age, 53.4 years; range, 47-61 years] and 12 hypertensive subjects [mean age, 55.4 years; range, 43-72 years]) were included in the study. When the data for all 19 subjects were pooled, ABP was significantly lower with irbesartan than placebo both during the day (120 [3]/79 [2] vs 127 [3]/85 [2] mm Hg; both, P < 0.01) and at night (systolic BP, 107 [4] vs 111 [4] mm Hg [P < 0.01] and diastolic BP, 71 [2] vs 75 [2] mm Hg [P < 0.05]). Compared with placebo, irbesartan was not associated with a significant change in GFR in either the normotensive or the hypertensive women. When the data for all 19 subjects were pooled, irbesartan was associated with a significant increase in ERPF compared with placebo (372 [21] vs324 [18] mL/min · 1.73 m(2); P < 0.05). When the hypertensive and normotensive women were considered separately, the effect was more pronounced in the hypertensive women than in the normotensive women, but the changes did not reach statistical significance. When the data for all subjects were pooled, irbesartan was associated with a significant increase in daytime urinary sodium excretion compared with placebo (135 [13] vs 106 [13] µmol/min; P < 0.05) and a significant decrease at night (109 [13] vs 136 [19] µmol/min; P < 0.05). Fractional excretion of lithium (FELi), an inverse marker of proximal sodium reabsorption, increased significantly during the daytime with irbesartan compared with placebo (47% [6.5%] vs 35% [4.7%]; P < 0.05). At nighttime, FELi was significantly higher in the hypertensive subjects receiving irbesartan compared with placebo (43% [7.2%] vs 29% [6.5%]; P < 0.05). The fractional distal reabsorption of sodium did not change significantly with irbesartan compared with placebo. CONCLUSIONS: The results from this study suggest that angiotensin II receptor blockade had a favorable impact on BP, renal hemodynamics, and renal sodium handling in these salt-replete postmenopausal women. Blockade of the renin-angiotensin system restored the normal pattern of renal response to high sodium intake in these women.

Identification of BARD1 splice-isoforms involved in human trophoblast invasion.

The tumor suppressor protein BARD1, originally discovered as BRCA1-binding protein, acts in conjunction with BRCA1 as ubiquitin ligase. BARD1 and BRCA1 form a stable heterodimer and dimerization, which is required for most tumor suppressor functions attributed to BRCA1. In addition, BARD1 has BRCA1-independent functions in apoptosis, and a role in control of tissue homeostasis was suggested. However, cancer-associated mutations of BARD1 are rare; on the contrary, overexpression of truncated BARD1 was found in breast and ovarian cancer and correlated with poor prognosis. Here we report that human cytotrophoblasts, which show a strong similarity with cancer cells in respect of their invasive behavior and capacity of matrix metalloprotease production, overexpress isoforms of BARD1 derived from differential splicing. We demonstrate that expression of BARD1 and its isoforms is temporally and spatially regulated by human chorionic gonadotropin and by hypoxia, both factors known to regulate the invasive phase and proliferation of cytotrophoblasts. Interestingly, we found a subset of BARD1 isoforms secreted by cytotrophoblasts. BARD1 repression by siRNAs, mitigates the interference of cytotrophoblasts with cell adhesion of collagen matrix-dependent epithelial cells, suggesting a role of BARD1 isoforms in extracellular matrix remodelling and in cytotrophoblasts invasion.

Factors regulating trophoblast invasion.

Implantation in the human is unique. This uniqueness is characterized on the maternal side by a spontaneous and massive decidualization of the endometrium and on the embryonic side by an almost unlimited invasive potential. Human embryos express an intrinsic invasive potential, which allows them to implant almost anywhere except in the endometrium because it protects itself from implantation. Human implantation is thus only possible during a limited period of time known as the implantation window. This mini review stresses the importance of studying trophoblast invasion into the endometrium as a model for human implantation. Cytotrophoblastic cells (CTB) can easily be isolated from first-trimester legal abortions and retain their invasive behavior when cultured in vitro. This model shows that matrix metalloproteinases (MMPs) are produced by CTB and are instrumental to their invasive behavior. Embryo implantation and tumor invasion use these same biochemical mediators for invasion. However, in contrast to tumor invasion, trophoblast invasion is limited both in time and space: it occurs during the first trimester of pregnancy and invasion does not go beyond the proximal third of the myometrium. Factors regulating MMP expression are of maternal and fetal origin.

The human cytotrophoblastic cell, a mononuclear chameleon.

The human placenta represents an abundant; easily accessible and unlimited study material (at birth a human placenta provides about 500 g of trophoblast). Cytotrophoblastic cells (CTB) are one constituent of the human placenta and represent epithelial cells with fascinating properties: They are able to fuse to form syncytia, can behave like immotile polarized epithelial cells, can phenocopy stromal fibroblasts or endothelial cells or undergo a mesenchymal-like transformation that converts them into non proliferative and highly invasive cells. Like a chameleon, CTB are thus able to adapt to their immediate environment by phenocopying their neighbor cells. This review describes the different routes that CTB follow during their differentiation pathways, the regulation of these at the molecular level, it gives also an overview of the pathologies associated with faulty pathways and describes the usual phenotypic markers used to identify the different CTB subsets. This review is intended to stimulate investigators not acquainted with the field of placental biology to use CTB as a model to study important biological functions in vitro, such as cell fusion, cell invasion and cell transformation.

Control of MMP-9 expression at the maternal-fetal interface.

Cytotrophoblastic cells (CTB) from first trimester placenta form columns of invasive CTB. This invasive behaviour is due to the ability of CTB to secrete matrix metalloproteinases (MMPs) since tissue inhibitor of MMP (TIMP) inhibits their invasiveness. Although CTB behave like metastatic cells, in vivo they are only transiently invasive (first trimester) and their invasion is normally limited only to the endometrium and to the proximal third of the myometrium. This temporal and spatial regulation of trophoblast invasion is believed to be mediated in an autocrine way by trophoblastic factors and in a paracrine way by uterine factors. Several types of regulators have been investigated: hormones, extra-cellular matrix glycoproteins and cytokines or growth factors. This review is not intended to be an exhaustive catalogue of potential regulators of trophoblastic MMP-9 secretion but is aimed at summarising the most important signalling pathways involved in MMP-9 regulation.

Localization and cellular distribution of pregnancy-associated plasma protein-a and major basic protein in human ovary and corpora lutea throughout the menstrual cycle.

OBJECTIVE: To assess the expression and cellular distribution of pregnancy-associated plasma protein-A (PAPP-A) and major basic protein (MBP) in human ovarian tissue during the menstrual cycle. DESIGN: Ovarian tissues (n = 50) and corpora lutea (n = 18) were obtained from patients undergoing hysterectomy/oophorectomy for benign conditions and tissue sections were immunostained for MBP and PAPP-A. SETTING: University medical center. INTERVENTION(S): Immunostaining of tissue sections using antibodies to PAPP-A and MBP. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence, distribution, and cellular co-localization of MBP and PAPP-A and to describe any variations in their expression during the menstrual cycle. RESULT(S): Major basic protein (MBP) is found in several ovarian cell types throughout the menstrual cycle. The MBP immunostaining of ovarian follicles varied depending on the size, with primordial follicles staining in the ooplasm with a lack of staining in the granulosa and theca cells. In the intermediate/mature follicles, MBP was immunolocalized in theca, but not in granulosa cells except in the mature follicles. Pregnancy-associated plasma protein-A (PAPP-A) was immunolocalized in primordial follicle ooplasm, theca externa of intermediate/mature follicles, and in granulosa cells with increased intensity as luteinization progressed. The luteal tissue is the major site of MBP and PAPP-A with highest intensity found during the midluteal phase associated with both small and large luteal cells. CONCLUSION(S): The expression and distinct pattern of MBP and PAPP-A cellular localization in human ovarian tissue during folliculogenesis and in luteal tissue suggest that their individual and combined actions in a cell specific fashion may play a role in growth and differentiation of theca, granulosa, and luteal cells.

Effect of hydrosalpinx fluid on secretion of trophoblastic matrix metalloproteinases.

OBJECTIVE: To determine if hydrosalpinx fluid affects trophoblastic metalloproteinases (MMPs) secretion. DESIGN: Measurement of the effect of hydrosalpinx and peritoneal fluids (as controls) added to the medium on the MMPs secreted by cytotrophoblastic cells. SETTING: Academic research center. PATIENT(S): Five samples of hydrosalpinx fluid were obtained at the time of ovocyte retrieval. Three samples of peritoneal fluids were collected at laparoscopic sterilization. MAIN OUTCOME MEASURE(S): The concentration and activity of MMP-2 and MMP-9, the concentration of the tissue inhibitor of metalloproteinases (TIMP-1), and the total gelatinolytic activity of the cytotrophoblastic cells were measured in the culture medium. RESULT(S): Hydrosalpinx significantly stimulated MMP-2, MMP-9, and TIMP-1. The net result was a significant stimulation of the total gelatinolytic activity. Peritoneal fluids increased MMP-2, MMP-9, and TIMP-1 concentrations, but the total gelatinolytic activity was not modified. CONCLUSION(S): In contrast to peritoneal fluids, hydrosalpinx stimulates the total gelatinolytic activity of cytotrophoblastic cells. This might indicate that the effect of hydrosalpinx on implantation rates may not be due to an inhibition of the capacity of an embryo to invade the endometrium. However, the stimulatory effect of hydrosalpinx on the net gelatinolytic activity could partly explain the increased incidence of ectopic pregnancies that have been described in the presence of hydrosalpinx.

Apoptosis in the first trimester human placenta: the role in maintaining immune privilege at the maternal-foetal interface and in the trophoblast remodelling.

Apoptosis has been proposed as a mechanism for maintaining immune privilege. Expression of Fas ligand (FasL) by the human trophoblast has been recently accepted as a mechanism providing protection against the lytic action of activated decidual immune cells expressing Fas receptor (FasR). Therefore, the purpose of this review was to determine the role of apoptosis in early pregnancy maintenance according to the latest literature. We used Medline literature search. The data suggest that apoptosis may serve as a previously unsuspected mechanism that induces tolerance of the foetal allograft against maternal immune system. Apoptosis of activated maternal immune cells occurs in the human decidua mainly through Fas-FasL or receptor for TNF-related apoptosis-inducing ligand (TRAIL-R)-TNF-related apoptosis-inducing ligand (TRAIL) signalling. This might be a defence mechanism against rejection of the foetal allograft by the maternal immune system. In addition, in this review contribution of programmed cell death to placental cell turnover and remodelling during first trimester of pregnancy is also discussed.

First trimester screening for trisomy 21; Do the parameters used detect more pathologies than just Down syndrome?

OBJECTIVE: To assess the value of first trimester maternal serum free beta human chorionic gonadotropin (beta hCG), pregnancy-associated plasma protein (PAPP-A) concentrations and nuchal translucency (NT) as predictors of pregnancy complications. DESIGN: A retrospective collaborative study of beta hCG, PAPP-A and NT between 10 and 14 weeks of pregnancy in patients in whom pregnancy was followed to term. Nuchal translucency, maternal serum PAPP-A and free beta hCG concentrations were measured in 1779 women with singleton pregnancies and without aneuploidies. Individual values were expressed as multiple of medians (MoM). Normal and abnormal pregnancies were compared for these parameters. RESULTS: Irrespective of the presence or absence of pregnancy-associated pathologies; there was no change in the median MoM for NT. The median MoM for free beta hCG was significantly increased in women with threatened abortions whereas the median MoMs for PAPP-A in women with spontaneous abortions or with pre-term deliveries were decreased significantly compared to normal pregnancies. These parameters have however no clinical usefulness as determined by receiver operator characteristics curves. CONCLUSION: Since PAPP-A is a protease that specifically degrades insulin-like growth factor binding proteins we would conclude that the control of the insulin-like growth factor system in the first trimester of pregnancy might play a key role in determining subsequent pregnancy outcome.

Accuracy of single measurements of pregnancy-associated plasma protein-A, human chorionic gonadotropin and progesterone in the diagnosis of early pregnancy failure.

BACKGROUND: Circulating human chorionic gonadotropin (hCG) and progesterone are commonly used as markers of abnormal pregnancies. Previous studies have shown that pregnancy-associated plasma protein-A (PAPP-A) was also depressed in extrauterine pregnancies (EUP). Previously, PAPP-A was measured with polyclonal antibodies which were later shown to recognise also the pro-form of major basic protein (pro-MBP). OBJECTIVE: To evaluate the clinical usefulness of PAPP-A measurements in early pregnancy. STUDY DESIGN: Circulating PAPP-A, hCG and progesterone were measured in patients with EUP (n=68), abnormal intrauterine pregnancies (abIUP, n=31) and normal intrauterine pregnancies (nIUP, n=72). Gestational age was 30-70 days from the last menstruation. RESULTS: For PAPP-A and hCG, a steep increase was observed from day 30 after last menstrual period onwards, this increase being much less important for abIUP and EUP. The values of PAPP-A and hCG were significantly decreased in abIUP and EUP, from 42 days after LMP onwards. There were no significant differences between abIUP and EUP. Progesterone concentration does not vary with amenorrhoea and was significantly lower in abIUP and EUP. Values in abIUP were significantly (P=0.02) lower compared with EUP for amenorrhoea above 42 days. ROC curves were constructed for amenorrhoea above 42 days. For a specificity of 99%, the sensitivity of PAPP-A, hCG and progesterone were 64.5, 93.3 and 76%, respectively. The threshold values were 14.3mIU/l, 10,400IU/l and 10.1ng/ml for PAPP-A, hCG and progesterone. CONCLUSION: We confirm the decrease of PAPP-A concentrations in pregnancy failure, but hCG and progesterone remain the best clinical tools.

Hemispheric specialization varies with EEG brain resting states and phase of menstrual cycle.

A growing body of behavioral studies has demonstrated that women's hemispheric specialization varies as a function of their menstrual cycle, with hemispheric specialization enhanced during their menstruation period. Our recent high-density electroencephalogram (EEG) study with lateralized emotional versus neutral words extended these behavioral results by showing that hemispheric specialization in men, but not in women under birth-control, depends upon specific EEG resting brain states at stimulus arrival, suggesting that hemispheric specialization may be pre-determined at the moment of the stimulus onset. To investigate whether EEG brain resting state for hemispheric specialization could vary as a function of the menstrual phase, we tested 12 right-handed healthy women over different phases of their menstrual cycle combining high-density EEG recordings and the same lateralized lexical decision paradigm with emotional versus neutral words. Results showed the presence of specific EEG resting brain states, associated with hemispheric specialization for emotional words, at the moment of the stimulus onset during the menstruation period only. These results suggest that the pre-stimulus EEG pattern influencing hemispheric specialization is modulated by the hormonal state.