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

Critical Role of Transcript Cleavage in Arabidopsis RNA Polymerase II Transcriptional Elongation

Transcript elongation factors associate with elongating RNA polymerase II (RNAPII) to control the efficiency of mRNA synthesis and consequently modulate plant growth and development. Encountering obstacles during transcription such as nucleosomes or particular DNA sequences may cause backtracking and transcriptional arrest of RNAPII. The elongation factor TFIIS stimulates the intrinsic transcript cleavage activity of the polymerase, which is required for efficient rescue of backtracked/arrested RNAPII. A TFIIS mutant variant (TFIISmut) lacks the stimulatory activity to promote RNA cleavage, but instead efficiently inhibits unstimulated transcript cleavage by RNAPII. We could not recover viable Arabidopsis (Arabidopsis thaliana) tfIIs plants constitutively expressing TFIISmut. Induced, transient expression of TFIISmut in tfIIs plants provoked severe growth defects, transcriptomic changes and massive, transcription-related redistribution of elongating RNAPII within transcribed regions toward the transcriptional start site. The predominant site of RNAPII accumulation overlapped with the 11 nucleosome, suggesting that upon inhibition of RNA cleavage activity, RNAPII arrest prevalently occurs at this position. In the presence of TFIISmut, the amount of RNAPII was reduced, which could be reverted by inhibiting the proteasome, indicating proteasomal degradation of arrested RNAPII. Our findings suggest that polymerase backtracking/arrest frequently occurs in plant cells, and RNAPII-reactivation is essential for correct transcriptional output and proper growth/development

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

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

Secretion of Hepatitis C Virus Envelope Glycoproteins Depends on Assembly of Apolipoprotein B Positive Lipoproteins

The density of circulating hepatitis C virus (HCV) particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB) positive and triglyceride rich lipoproteins (TRL) likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP) containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1–E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed

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