The association of PTSD with physical and mental health functioning and disability (VA Cooperative Study #569: the course and consequences of posttraumatic stress disorder in Vietnam-era Veteran twins)

Purpose

To assess the relationship of posttraumatic stress disorder (PTSD) with health functioning and disability in Vietnam-era Veterans.

Methods

A cross-sectional study of functioning and disability in male Vietnam-era Veteran twins. PTSD was measured by the Composite International Diagnostic Interview; health functioning and disability were assessed using the Veterans RAND 36-Item Health Survey (VR-36) and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). All data collection took place between 2010 and 2012.

Results

Average age of the 5,574 participating Veterans (2,102 Vietnam theater and 3,472 non-theater) was 61.0 years. Veterans with PTSD had poorer health functioning across all domains of VR-36 and increased disability for all subscales of WHODAS 2.0 (all p < .001) compared with Veterans without PTSD. Veterans with PTSD were in poorer overall health on the VR-36 physical composite summary (PCS) (effect size = 0.31 in theater and 0.47 in non-theater Veterans; p < .001 for both) and mental composite summary (MCS) (effect size = 0.99 in theater and 0.78 in non-theater Veterans; p < .001 for both) and had increased disability on the WHODAS 2.0 summary score (effect size = 1.02 in theater and 0.96 in non-theater Veterans; p < .001 for both). Combat exposure, independent of PTSD status, was associated with lower PCS and MCS scores and increased disability (all p < .05, for trend). Within-pair analyses in twins discordant for PTSD produced consistent findings.

Conclusions

Vietnam-era Veterans with PTSD have diminished functioning and increased disability. The poor functional status of aging combat-exposed Veterans is of particular concern.     

The Associations Of Maternal Emotion Dysregulation And Early Child Dissociative Behaviors

ABSTRACT

Although dissociation is believed to develop in early childhood, there is little research prospectively examining childhood dissociation or parental contributions related to its development. The current study sought to examine parent factors prospectively related to changes in dissociation symptoms in childhood. The current study sampled 68 mother-child dyads at two time points, when children were 3–4 and then 5–6 years, in which mothers with emotion dysregulation were oversampled. Maternal emotion dysregulation was assessed at both time points. Maternal dissociation was assessed only at time two. Child dissociation was assessed at each time point using a modified subscale of the Child Behavioral Checklist. Results showed moderate stability in childhood dissociation across time points. Further, maternal emotion dysregulation and dissociation were both significantly correlated with children’s dissociation. Accounting for several covariates, time one maternal emotion dysregulation was prospectively associated with preschoolers’ dissociative behaviors at 5–6 years old. The present work suggests that symptoms of dissociation can be observed early in childhood and that maternal factors play an early role in the development of dissociation in children.     

Potential for Use of the Seegene Anyplex MTB/NTM Real-Time Detection Assay in a Regional Reference Laboratory

Requests for direct molecular diagnosis of mycobacterial disease are increasingly warranted. The Anyplex MTB/NTM assay demonstrates sensitivities, specificities, and positive and negative predictive values of 1.00, 0.96, 0.93, and 1.00 for Mycobacterium tuberculosis complex (MTBC) and 1.00, 0.97, 0.75, and 1.00 for nontuberculous mycobacteria (NTM) detection, respectively, making it a suitable screening test for mycobacterial detection.     

Integrin-directed modulation of macrophage responses to biomaterials

Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (α_Mβ₂) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (∼30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (∼45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials.     

UBQLN2 mutations are not a frequent cause of amyotrophic lateral sclerosis in Ireland

Mutations in UBQLN2 have been shown to be a cause of dominant X-linked amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary across ALS populations. We screened UBQLN2 for mutations in a final cohort of 150 Irish ALS patients. Individuals who were from families with male-to-male transmission or who carried pathogenic hexanucleotide repeat expansions in C9orf72 were excluded. Apart from common synonymous variation, no sequence variants in UBQLN2 were observed. Mutations in UBQLN2 are therefore not a frequent cause of ALS in the Irish population.     

Age-related decline in white matter integrity in a mouse model of tauopathy: an in vivo diffusion tensor magnetic resonance imaging study

Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion anisotropy indices in a mouse model of human tauopathy (rTg4510) and nontransgenic (nonTg) control mice at the age of 2.5, 4.5, and 8 months. Similar to previous DT-MRI studies in AD subjects, 8-month-old rTg4510 mice showed lower fractional anisotropy (FA) values in WM structures than nonTg. The low WM FA in rTg4510 mice was observed in the genu and splenium of the corpus callosum, anterior commissure, fimbria, and internal capsule and was associated with a higher radial diffusivity than nonTg. Interestingly, rTg4510 mice showed lower estimates for the mode of anisotropy than controls at 2.5 months suggesting that changes in this diffusivity metric are detectable at an early stage preceding severe tauopathy. Immunogold electron microscopy partly supports our diffusion tensor imaging findings. At the age of 4 months, rTg4510 mice show axonal tau inclusions and unmyelinated processes. At later ages (12 months and 14 months) we observed inclusions in myelin sheath, axons, and unmyelinated processes, and a “disorganized” pattern of myelinated fiber arrangement with enlarged inter-axonal spaces in rTg4510 but not in nonTg mice. Our data support a role for the progression of tau pathology in reduced WM integrity measured by DT-MRI. Further in vivo DT-MRI studies in the rTg4510 mouse should help better discern the detailed mechanisms of reduced FA and anisotropy mode, and the specific role of tau during neurodegeneration.     

A Lifecycle Approach to HIV Prevention in African Women and Children

Effective biomedical and structural HIV prevention approaches are being implemented throughout sub-Saharan Africa. A “lifecycle approach” to HIV prevention recognizes the interconnectedness of the health of women, children and adolescents, and prioritizes interventions that have benefits across these populations. We review new biomedical prevention strategies for women, adolescents and children, structural prevention approaches, and new modalities for eliminating infant HIV infection, and discuss the implications of a lifecycle approach for the success of these methods. Some examples of the lifecycle approach include evaluating education and HIV prevention strategies among adolescent girls not only for their role in reducing risk of HIV infection and early pregnancy, but also to promote healthy adolescents who will have healthier future children. Similarly, early childhood interventions such as exclusive breastfeeding not only prevent HIV, but also contribute to better child and adolescent health outcomes. The most ambitious biomedical infant HIV prevention effort, Option B+, also represents a lifecycle approach by leveraging the prevention benefits of optimal HIV treatment for mothers; maternal survival benefits from Option B+ may have ultimately more health impact on children than the prevention of infant HIV in isolation. The potential for synergistic and additive benefits of lifecycle interventions should be considered when scaling up HIV prevention efforts in sub-Saharan Africa.