Clarifying the role of three-dimensional transvaginal sonography in reproductive medicine: an evidenced-based appraisal

This overview describes and illustrates the clinical applications of three-dimensional transvaginal sonography in reproductive medicine. Its main applications include assessment of uterine anomalies, intrauterine pathology, tubal patency, polycystic ovaries, ovarian follicular monitoring and endometrial receptivity. It is also useful for detailed evaluation of failed and/or ectopic pregnancy. Three-dimensional color Doppler sonography provides enhanced depiction of uterine, endometrial, and ovarian vascularity

Clinical approach for the classification of congenital uterine malformations

A more objective, accurate and non-invasive estimation of uterine morphology is nowadays feasible based on the use of modern imaging techniques. The validity of the current classification systems in effective categorization of the female genital malformations has been already challenged. A new clinical approach for the classification of uterine anomalies is proposed. Deviation from normal uterine anatomy is the basic characteristic used in analogy to the American Fertility Society classification. The embryological origin of the anomalies is used as a secondary parameter. Uterine anomalies are classified into the following classes: 0, normal uterus; I, dysmorphic uterus; II, septate uterus (absorption defect); III, dysfused uterus (fusion defect); IV, unilateral formed uterus (formation defect); V, aplastic or dysplastic uterus (formation defect); VI, for still unclassified cases. A subdivision of these main classes to further anatomical varieties with clinical significance is also presented. The new proposal has been designed taking into account the experience gained from the use of the currently available classification systems and intending to be as simple as possible, clear enough and accurate as well as open for further development. This proposal could be used as a starting point for a working group of experts in the field

Impact of discrimination on health among adolescent immigrant minorities in Europe: The role of perceived discrimination by police and security personnel

Previous research has shown negative effects of discrimination on ethnic minority members’ health and well-being. In this study, we examined cross-sectional and longitudinal effects of discrimination by members of the police and security personnel over and above other types of discrimination and ethnic victimization on the health of immigrant minority students from three different European countries (N = 4,334 immigrant students from 580 ethnically mixed school classes in Germany, the Netherlands, and Sweden). Results indicate that perceptions of ethnic victimization in the school (measured via social network data) as well as three types of discrimination outside school (discrimination in clubs, public transportation as well as by the police and private security) are associated with current and future negative health outcomes (i.e., psychosomatic problems) in immigrant minority students. Among the different types of discrimination, discrimination by the police and private security personnel was most common and had the most negative effect on immigrant minority students’ health. Practical and political implications of our findings as well as differences in discrimination and violence by the police between the US and Europe are discussed

Ketamine-Induced Dissociative Effect Associates with the Change of Mean Global Neuronal Activity

Background Ketamine-induced antidepressant effect has been reported in animal and human studies. The rapid efficacy of ketamine, a non-completive NMDA receptor antagonist, indicates different mechanisms compared to currently available drugs. However, the accompanying adverse effects and association to antidepressant properties remain unknown. This study investigated the change of mean global neuronal activity, also known as global signal (GS), 1h and 24h after ketamine infusion, and the relationship with the acute dissociative experience. Methods In a randomized, double-blind, placebo-controlled study, 81 healthy controls received single subanesthetic dose of ketamine (0.5 mg/kg within 40 min) or saline. For each subject, resting-state fMRI were acquired at baseline, 1h, and 24h post-infusion at 7T scanner. The dissociative side effects were evaluated using Clinician Administered Dissociative States Scale (CADSS) right after the infusion. EPI data were preprocessed using scripts from the 1000 functional connectome project (FCP, version 1.1-beta). GS was extracted and transformed into Z-Score, and its change was assessed by implementing Teager-kaiser operator. Thirty-two ketamine and thirty placebo subjects were tested at threshold p<0.05. Results Larger fluctuation of GS was found 1 hour after ketamine administration (t=2.09, p=0.04). Moreover, in ketamine group, the GS at 1 hour associated with total CADSS (r=−0.353, p=0.04), more specifically with subscale derealization (r=−0.466, p=0.007). Conclusions GS changes and associated adverse effects were observed only in the acute phase after ketamine administration. This could imply that long-term antidepressant results are downstream effects from the acute phase, and GS can be seen as an early marker of underlying neuronal activity induced by ketamine

Brain-derived neurotrophic factor (BDNF) as a potential biomarker for resting-state network remodeling after ketamine infusion

Introduction Ketamine, an NMDAR antagonist, produces fast antidepressant response with a maximum efficacy 24h after infusion [1]. Animal studies showed that ketamine generates higher synaptic plasticity via induction of Brain-derived neurotrophic factor (BDNF) [2]. Patients with depression have lower blood level of BDNF and show an increase after ketamine infusion [4]. Besides, depressed patients have hyperconnectivity within the Default mode network (DMN) [5]. Ketamine decreases the Functional Connectivity (FC) in healthy subjects between posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC), two main regions within DMN [6], revealing possible mechanisms of the antidepressant effect. Methods In a double-blind study, 81 healthy subjects received infusion of either ketamine (0.5 mg/kg) or saline. In each subject, resting state fMR images (TR= 2.8s, voxel size= 2 × 2 × 2 mm3, 7T ) and plasma blood samples were acquired at baseline and 24h post-infusion. Ketamine (n=32) and placebo (n=30) groups were preprocessed using scripts developed in the functional connectome 1000 project. Dorsal PCC (dPCC) was chosen as a priori seed region [6] and FC maps were calculated. The mean FC value was extracted from clusters showing significant change after infusion. Extracted FC values were correlated with the plasma BDNF at 24h (n=45). Results 24h after infusion, ketamine treated subjects showed higher BDNF level compared to placebo (p=0.015). A decrease in FC between the dPCC and both dorsolateral PFC (p=0.005 FWE) and two cluster in mPFC (p=0.001 p=0.030 FWE) was observed 24h after infusion. Subjects with higher BDNF level after ketamine show significantly higher FC disconnection between dorsal PCC and mPFC (r= 0.64, p=0.006). Conclusions Ketamine decreases FC within the DMN and increases BDNF 24h after ketamine. Higher BDNF level correlates with stronger FC disconnection between anterior (mPFC) and posterior (dPCC) part of DMN. This finding highlights the role of BDNF as a potential biomarker for network remodeling in the brain. 1 Zarate et al. (2006) A Randomized Trial of an N-methyl-D- aspartate Antagonist in Treatment-Resistant Major Depression. 2 Duman et al. (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. 3 Haile (2013) Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. 4 Kaiser et al. (2015). Large-scale network dysfunction in major depressive disorder. 5 Scheidegger et al. (2012). Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action

Neuronal glutamatergic changes and peripheral markers of cytoskeleton dynamics change synchronically 24 h after sub-anaesthetic dose of ketamine in healthy subjects

Ketamine acts as a rapid–acting antidepressant by restoring glutamatergic deficits and activating synaptic plasticity processes, with peak activity 24 h after infusion. Microtubule dynamics are known to play a key role in modulation of cytoskeleton and synaptic plasticity, as well as in signalling events in peripheral blood cells. Here, we correlated ketamine-induced change in glutamate/creatinine (Glu/Cr) levels in the pregenual anterior cingulate cortex (pgACC) with peripheral markers of microtubule dynamics, namely acetylated α-tubulin (Acet-Tub), with particular attention to gender specificity. Eighty healthy controls (age = 25.89 ± 5.29, 33 women) were administered intravenous infusion of either ketamine (0.5 mg/kg) or placebo (saline). Blood samples were obtained at baseline and 24 h after infusion and plasma levels of Acet-Tub and transferrin (TRF; loading control) were measured via infrared western blotting. Glu/Cr levels were measured via high-field (7 T) proton magnetic resonance spectroscopy [1H-MRS] in the pgACC at the same time points. Gender differences were observed in baseline Acet–Tub/TRF levels (p < 0.001), and an interaction of time by treatment by gender (F = 5.13, p = 0.027) was found, with a significant increase in Acet–Tub/TRF for ketamine group in females only (p = 0.038). Ketamine-induced gender-independent Glu/Cr changes at 24 h (F(1, 69) = 4.08, p = 0.047), and changes in the pgACC were negatively correlated with the Acet-Tub/TRF expression (r= -0.464, p = 0.010) in the ketamine group, in which, separated by sex, only women showed significant correlation. Our findings indicate a temporal association between changes in central ketamine-induced glutamatergic effects and peripheral markers of cytoskeleton reorganization, particularly in females