Reducing childbirth-related intrusive memories and PTSD symptoms via a single-session behavioural intervention including a visuospatial task: A proof-of-principle study.

Intrusive memories (IMs) of traumatic events are a key symptom of posttraumatic stress disorder (PTSD), and contribute to its maintenance. This translational proof-of-principle study tested whether a single-session behavioural intervention reduced the number of childbirth-related IMs (CB-IMs) and childbirth-related PTSD (CB-PTSD) symptoms, in women traumatised by childbirth. The intervention was assumed to disrupt trauma memory reconsolidation. In this pre-post study, 18 participants, whose traumatic childbirth had occurred between seven months and 6.9 years before, received an intervention combining childbirth-related reminder cues (including the return to maternity unit) with a visuospatial task. They recorded their daily CB-IMs in the two weeks pre-intervention (diary 1), the two weeks post-intervention (diary 2; primary outcome), and in week 5 and 6 post-intervention (diary 3). CB-PTSD symptom severity was assessed five days pre-intervention and one month post-intervention. Compared to diary 1, 15/18 participants had ≥ 50% fewer CB-IMs in diary 2. The median (IQR) reduction of the number of CB-IMs was 81.89% (39.58%) in diary 2, and persisted in diary 3 (n = 17). At one month post-intervention, CB-PTSD symptom severity was reduced by ≥ 50% in 10/18 participants. Of the 8 participants with a CB-PTSD diagnosis pre-intervention, none met diagnostic criteria post-intervention. The intervention was rated as highly acceptable. The design limits the causal interpretation of observed improvements. This is the first time such a single-session behavioural intervention was tested for old and real-life single-event trauma. The promising results justify a randomized controlled trial, and may be a first step toward an innovative CB-PTSD treatment

Prenatal insomnia and childbirth-related PTSD symptoms: A prospective population-based cohort study.

Certain populations are at high risk of experiencing a traumatic event and developing post-traumatic stress disorder (PTSD). Yet, primary preventive interventions against PTSD are lacking. It is therefore crucial to identify pre-traumatic risk factors, which could be targeted with such interventions. Insomnia may be a good candidate, but studies on civilians are sparse. Furthermore, the mechanisms at stake in the relationship between pre-traumatic insomnia and PTSD symptoms are unclear. This prospective population-based cohort study (n = 1,610) examined the relationship between insomnia symptoms at 32 weeks of pregnancy and childbirth-related PTSD (CB-PTSD) symptoms at eight weeks postpartum. Postnatal insomnia symptoms, prenatal psychological symptoms (depression, anxiety, PTSD, fear of childbirth), subjective birth experience (SBE) and birth medical severity were included as covariates in the analyses, which were based on a Piecewise Structural Equation Modelling approach. The relationship between prenatal insomnia and CB-PTSD symptoms was mediated by negative SBE and postnatal insomnia symptoms. All relationships involving insomnia symptoms had small or very small effect sizes. This study used self-report questionnaires. Postnatal insomnia and CB-PTSD symptoms were concurrently measured. Prenatal insomnia symptoms may impair the ability to cope with a difficult birth experience and contribute to postnatal insomnia, a risk factor for CB-PTSD. Thus, prenatal insomnia symptoms may be a promising target for CB-PTSD primary preventive interventions, although other prenatal psychological symptoms could also be considered. Even beyond the perinatal context, future studies on pre-traumatic insomnia and PTSD should include post-traumatic insomnia as a covariate

Document image segmentation using a multiresolution approach. Accurate text line extraction

An overall scheme and related algorithms performing accurate text lines extraction from an image of document are described in this paper The type of documents concerned here is very complex, with totally unconstrained data . Postal objects, especially the so-calledfiatobjects, i.e. : large envelopes, magazines, . . . are within this kind of documents. Three main phases have been considered to achieve the overall function . First of all, areas of interest are located using a multiresolution approach allowing to preserve from large variability of text features . This is performed directly on the gray-level image . A binarization stage, taking advantage of the results of the localization, is next performed to extract the lines . At last, a post-segmentation involving the located areas in the gray-level images and structural features extracted from the lines allows to deal with severe cases such as overlapping lines induced by handwritten texts . Examples related to text line extraction on postal objects are illustrating this paper.Cet article présente une méthodologie et des outils de traitement permettant de localiser puis d'extraire précisément les lignes de texte contenues dans l'image d'un document. La classe des documents visés est de type document très complexe, leurs contenus étant totalement non contraints. Globalement la méthodologie s'articule autour de trois étapes clés. La première est une localisation des zones d'intérêt. Elle est réalisée directement sur l'image en niveaux de gris et utilise une approche multirésolution garantissant une grande robustesse vis-à-vis de la très forte variabilité des textes: taille, disposition, présentation. Une étape de binarisation réalisée séparément pour chaque zone d'intérêt permet dans une seconde phase l'extraction proprement dite des lignes de texte. Enfin, une post-segmentation faisant coopérer la localisation initiale et des caractéristiques structurelles extraites de la ligne permet de traiter les cas très perturbants pour la lecture du chevauchement de lignes sur de l'écriture manuscrite. Des exemples relevant de la problématique de l'extraction des lignes du bloc adresse sur objets postaux (grandes lettres, magazines) illustrent cet article

The Lausanne Infant Crying Stress Paradigm: Validation of an Early Postpartum Stress Paradigm with Women at Low vs. High Risk of Childbirth-Related Posttraumatic Stress Disorder.

Stress reactivity is typically investigated in laboratory settings, which is inadequate for mothers in maternity settings. This study aimed at validating the Lausanne Infant Crying Stress Paradigm (LICSP) as a new psychosocial stress paradigm eliciting psychophysiological stress reactivity in early postpartum mothers (n = 52) and to compare stress reactivity in women at low (n = 28) vs. high risk (n = 24) of childbirth-related posttraumatic stress disorder (CB-PTSD). Stress reactivity was assessed at pre-, peri-, and post-stress levels through salivary cortisol, heart rate variability (high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio), and perceived stress via a visual analog scale. Significant time effects were observed for all stress reactivity outcomes in the total sample (all p < 0.01). When adjusting for perceived life threat for the infant during childbirth, high-risk mothers reported higher perceived stress (p < 0.001, d = 0.91) and had lower salivary cortisol release (p = 0.023, d = 0.53), lower LF/HF ratio (p < 0.001, d = 0.93), and marginally higher HF power (p = 0.07, d = 0.53) than low-risk women. In conclusion, the LICSP induces subjective stress and autonomic nervous system (ANS) reactivity in maternity settings. High-risk mothers showed higher perceived stress and altered ANS and hypothalamic-pituitary-adrenal reactivity when adjusting for infant life threat. Ultimately, the LICSP could stimulate (CB-)PTSD research

The relationship between early administration of morphine or nitrous oxide gas and PTSD symptom development.

Posttraumatic Stress Disorder (PTSD) is a debilitating mental health disorder. Certain drugs, such as morphine and nitrous oxide gas (N <sub>2</sub> O), are administered to individuals who just experienced a traumatic event (e.g., soldiers, injured civilians). It is therefore crucial to understand if they incidentally affect PTSD symptom development. Furthermore, such observations could pave the way for the development of pharmacological prevention strategies of PTSD. In this prospective population-based cohort study (n = 2,070), we examined the relationship between morphine or N <sub>2</sub> O administration during childbirth, and subsequent childbirth-related PTSD symptoms at eight weeks postpartum. Pain during labour, prior PTSD symptoms, and birth medical severity were included as covariates in the analyses. In women who developed PTSD symptoms, N <sub>2</sub> O administration during childbirth predicted reduced PTSD symptom severity (p < .001, small to medium effect size). A similar tendency was observed for morphine, but was not significant (p < .065, null to small effect size). Both drugs predicted increased PTSD symptoms when combined with severe pain during labour. This study was observational, thus drug administration was not randomised. Additionally, PTSD symptoms were self-reported. Peritraumatic N <sub>2</sub> O administration may reduce subsequent PTSD symptom severity and thus be a potential avenue for PTSD secondary prevention. This might also be the case for morphine. However, the role of severe peritraumatic pain in context of drug administration deserves further investigation

Control of Cognate Sense mRNA Translation by cis-Natural Antisense RNAs.

Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcribed from the opposite DNA strand, constitute an important group of noncoding RNAs. Whereas several examples of cis-NATs regulating the expression of their cognate sense gene are known, most cis-NATs function by altering the steady-state level or structure of mRNA via changes in transcription, mRNA stability, or splicing, and very few cases involve the regulation of sense mRNA translation. This study was designed to systematically search for cis-NATs influencing cognate sense mRNA translation in Arabidopsis (Arabidopsis thaliana). Establishment of a pipeline relying on sequencing of total polyA <sup>+</sup> and polysomal RNA from Arabidopsis grown under various conditions (i.e. nutrient deprivation and phytohormone treatments) allowed the identification of 14 cis-NATs whose expression correlated either positively or negatively with cognate sense mRNA translation. With use of a combination of cis-NAT stable over-expression in transgenic plants and transient expression in protoplasts, the impact of cis-NAT expression on mRNA translation was confirmed for 4 out of 5 tested cis-NAT:sense mRNA pairs. These results expand the number of cis-NATs known to regulate cognate sense mRNA translation and provide a foundation for future studies of their mode of action. Moreover, this study highlights the role of this class of noncoding RNAs in translation regulation

Single-session visuospatial task procedure to prevent childbirth-related posttraumatic stress disorder: a multicentre double-blind randomised controlled trial

Preventive evidence-based interventions for childbirth-related posttraumatic stress disorder (CB-PTSD) are lacking. Yet, 18.5% of women develop CB-PTSD symptoms following an unplanned caesarean section (UCS). This two-arm, multicentre, double-blind superiority trial tested the efficacy of an early single-session intervention including a visuospatial task on the prevention of maternal CB-PTSD symptoms. The intervention was delivered by trained maternity clinicians. Shortly after UCS, women were included if they gave birth to a live baby, provided consent, and perceived their childbirth as traumatic. Participants were randomly assigned to the intervention or attention-placebo group (allocation ratio 1:1). Assessments were done at birth, six weeks, and six months postpartum. Group differences in maternal CB-PTSD symptoms at six weeks (primary outcomes) and six months postpartum (secondary outcomes) were assessed with the self-report PTSD Checklist for DSM-5 (PCL-5) and by blinded research assessors with the Clinician-administered PTSD scale for DSM-5 (CAPS-5). Analysis was by intention-to-treat. The trial was prospectively registered (ClinicalTrials.gov, NCT03576586). Of the 2068 women assessed for eligibility, 166 were eligible and 146 were randomly assigned to the intervention (n = 74) or attention-placebo control group (n = 72). For the PCL-5, at six weeks, a marginally significant intervention effect was found on the total PCL-5 PTSD symptom count (β = -0.43, S.E. = 0.23, z = -1.88, p < 0.06), and on the intrusions (β = -0.73, S.E. = 0.38, z = -1.94, p < 0.0525) and arousal (β = -0.55, S.E. = 0.29, z = -1.92, p < 0.0552) clusters. At six months, a significant intervention effect on the total PCL-5 PTSD symptom count (β = -0.65, S.E. = 0.32, z = -2.04, p = 0.041, 95%CI[-1.27, -0.03]), on alterations in cognition and mood (β = -0.85, S.E. = 0.27, z = -3.15, p = 0.0016) and arousal (β = -0.56, S.E. = 0.26, z = -2.19, p < 0.0289, 95%CI[-1.07, -0.06]) clusters appeared. No group differences on the CAPS-5 emerged. Results provide evidence that this brief, single-session intervention carried out by trained clinicians can prevent the development of CB-PTSD symptoms up to six months postpartum

Th1 Disabled Function in Response to TLR4 Stimulation of Monocyte-Derived DC from Patients Chronically-Infected by Hepatitis C Virus

Background: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC) function has thus been suspected, but this remains a controversial issue. Methods and Findings: Here we show that monocyte-derived DC (MoDC) from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNc secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNc secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1b. Addition of MIP-1b on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1b secretion by HCV monocytes participates in the Th1 defect of DC. Conclusions: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. Thi

Human cell types important for Hepatitis C Virus replication in vivo and in vitro. Old assertions and current evidence

Hepatitis C Virus (HCV) is a single stranded RNA virus which produces negative strand RNA as a replicative intermediate. We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA. Studies using in situ hybridization, immunofluorescence, immunohistochemistry, and quasispecies analysis also demonstrated the presence of replicating HCV in various extrahepatic human tissues, and provide evidence that HCV replicates in macrophages, B cells, T cells, and other extrahepatic tissues. We also analyzed both short term and long term in vitro systems used to culture HCV. These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication. It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro