Effects of cognitive processing therapy on PTSD-related negative cognitions in veterans with military sexual trauma.

Treating post-traumatic stress disorder (PTSD) related to military sexual trauma (MST) continues to be a priority in veteran populations. Because negative cognitions (NCs) contribute to PTSD severity and treatment, further understanding of how PTSD and related NCs can be addressed and changed within an MST sample is important. Our study analyzed 45 participants who received either cognitive processing therapy (n = 32) or present centered therapy (n = 13). Participants who received cognitive processing therapy had significantly lower NCs scores post-treatment and at follow-up sessions than participants in the present centered therapy condition (p < 0.05). In addition, NCs were positively correlated with PTSD severity (p < 0.05). Implications for future research are discussed for both MST-related and non-MST-related PTSD.

Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts.

UNLABELLED: Intron-containing mRNAs are subject to restricted nuclear export in higher eukaryotes. Retroviral replication requires the nucleocytoplasmic transport of both spliced and unspliced RNA transcripts, and RNA export mechanisms of gammaretroviruses are poorly characterized. Here, we report the involvement of the nuclear export receptor NXF1/TAP in the nuclear export of gammaretroviral RNA transcripts. We identified a conserved cis-acting element in the pol gene of gammaretroviruses, including murine leukemia virus (MLV) and xenotropic murine leukemia virus (XMRV), named the CAE (cytoplasmic accumulation element). The CAE enhanced the cytoplasmic accumulation of viral RNA transcripts and the expression of viral proteins without significantly affecting the stability, splicing, or translation efficiency of the transcripts. Insertion of the CAE sequence also facilitated Rev-independent HIV Gag expression. We found that the CAE sequence interacted with NXF1, whereas disruption of NXF1 ablated CAE function. Thus, the CAE sequence mediates the cytoplasmic accumulation of gammaretroviral transcripts in an NXF1-dependent manner. Disruption of NXF1 expression impaired cytoplasmic accumulations of both spliced and unspliced RNA transcripts of XMRV and MLV, resulting in their nuclear retention or degradation. Thus, our results demonstrate that gammaretroviruses use NXF1 for the cytoplasmic accumulation of both spliced and nonspliced viral RNA transcripts. IMPORTANCE: Murine leukemia virus (MLV) has been studied as one of the classic models of retrovirology. Although unspliced host messenger RNAs are rarely exported from the nucleus, MLV actively exports unspliced viral RNAs to the cytoplasm. Despite extensive studies, how MLV achieves this difficult task has remained a mystery. Here, we have studied the RNA export mechanism of MLV and found that (i) the genome contains a sequence which supports the efficient nuclear export of viral RNAs, (ii) the cellular factor NXF1 is involved in the nuclear export of both spliced and unspliced viral RNAs, and, finally, (iii) depletion of NXF1 results in nuclear retention or degradation of viral RNAs. Our study provides a novel insight into MLV nuclear export.

A randomized clinical trial of cognitive processing therapy for veterans with PTSD related to military sexual trauma.

In this randomized controlled clinical trial, the authors evaluated the effectiveness of cognitive processing therapy (CPT) in the treatment of self-reported and clinician-assessed posttraumatic stress disorder (PTSD) related to military sexual trauma (MST), along with depressive symptoms. Eighty-six veterans (73 female, 13 male) randomly assigned to receive 12 individual sessions of either CPT or present-centered therapy (PCT) were included in analyses. Blinded assessments occurred at baseline, posttreatment, and 2, 4, and 6 months posttreatment. Mixed-effects model analysis revealed a significant interaction between groups (p = .05, d = -0.85): At posttreatment, veterans who received CPT had a significantly greater reduction in self-reported, but not clinician-assessed, PTSD symptom severity compared to veterans who received PCT. All three primary outcome measures improved significantly, both clinically and statistically, across time in both treatment groups. Pre- and posttreatment effect sizes were mostly moderate to large (d = 0.30-1.02) and trended larger in the CPT group. Although the study was impacted by treatment fidelity issues, results provide preliminary evidence for the effectiveness of CPT in reducing self-reported PTSD symptoms in a population of veterans with MST, expanding on established literature that has demonstrated the effectiveness of CPT in treating PTSD related to sexual assault in civilian populations.

In vivo efficacy of a chimeric peptide derived from the conserved region of the M protein against group C and G streptococci.

The J8 peptide from the conserved region of the M protein protects against group A streptococcus infections. In this study, we demonstrate that vaccination with a J8-containing formulation induces IgG that recognizes and binds group C and G streptococci. Moreover, this formulation has the potential to provide protection against infections caused by these organisms.

Long-term infection and vertical transmission of a gammaretrovirus in a foreign host species.

Increasing evidence has indicated natural transspecies transmission of gammaretroviruses; however, viral-host interactions after initial xeno-exposure remain poorly understood. Potential association of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome has attracted broad interests in this topic. Although recent studies have indicated that XMRV is unlikely a human pathogen, further understanding of XMRV xenoinfection would allow in vivo modeling of the initial steps of gammaretroviral interspecies transmission, evolution and dissemination in a new host population. In this study, we monitored the long-term consequences of XMRV infection and its possible vertical transmission in a permissive foreign host, wild-derived Mus pahari mice. One year post-infection, XMRV-infected mice showed no notable pathological changes, while proviral DNA was detected in three out of eight mice. XMRV-infected mice remained seropositive throughout the study although the levels of gp70 Env- and p30 capsid-specific antibodies gradually decreased. When vertical XMRV transmission was assessed, no viremia, humoral immune responses nor endogenization were observed in nine offspring from infected mothers, yet one offspring was found PCR-positive for XMRV-specific sequences. Amplified viral sequences from the offspring showed several mutations, including one amino acid deletion in the receptor binding domain of Env SU. Our results therefore demonstrate long-term asymptomatic infection, low incidence of vertical transmission and limited evolution of XMRV upon transspecies infection of a permissive new host, Mus pahari.

Predictors of suicidal ideation in veterans with PTSD related to military sexual trauma.

Predictors of suicidal ideation (SI) were examined in a sample of veterans (N = 128) diagnosed with posttraumatic stress disorder (PTSD) related to military sexual trauma. Suicidal ideation was predicted by both depressive symptom severity and posttraumatic symptom severity in separate correlation analyses. When controlling for the effects of depressive and posttraumatic symptom severity on one another in the prediction of SI in a single multiple regression model, however, only depressive symptoms independently predicted SI. These analyses suggest that the contribution of PTSD symptom severity to the prediction of SI is reduced by adding depressive symptoms. Hyperarousal symptom severity, however, was found in a separate multiple regression model to contribute independently to the prediction of SI controlling for depressive symptom severity.

Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine.

Infection with Streptococcus pyogenes, commonly known as group A Streptococcus (GAS), is responsible for acute and postinfectious complications, including rheumatic fever and rheumatic heart disease (RHD). RHD is a global health burden, and Australia's indigenous population has one of the highest incidences of RHD worldwide. A potential peptide (J14) vaccine candidate has been previously identified from the C-terminal region of the M protein. However, such peptide-based vaccine development is hampered by a lack of carriers and adjuvants suitable for humans use. We have developed a fully synthetic peptide subunit vaccine candidate based on polyacrylate dendritic polymer. Intranasal administration of this nanoparticulate construct without additional adjuvant induced J14-specific IgG, which was also capable of in vitro opsonization of GAS, highlighting the potential of self-adjuvanting polyacrylate nanoparticle-based construct as a peptide vaccine delivery platform that may afford promising opportunities for treating systemic GAS infection. FROM THE CLINICAL EDITOR: Polyacrylate dendrimers offer a unique approach to a nasally administered vaccine for addressing rheumatic heart disease. This paper describes the delivery of the J14 peptide, a C-terminal derivative of M-protein in group A Streptococcus.