The experience of mental death: the core feature of complex posttraumatic stress disorder

Exposure to extreme interpersonal stress, exemplified by the experience of torture, represents a threat to the psychological integrity of the victim. The experience is likely to result in mental death, in the loss of the victim's pretrauma identity. Mental death is characterized by loss of core beliefs and values, distrust, and alienation from others, shame and guilt, and a sense of being permanently damaged. Mental death is a primary feature of a distinct posttrauma syndrome, complex posttraumatic stress disorder (PTSD), which is refractory to standard exposure therapies. We identify cognitive mechanisms that mediate the symptoms of complex PTSD, and suggest how current treatments need to be modified to obtain enhanced treatment outcomes.     

BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses

Binding of the TNF family member, B cell activating factor (BAFF), to its receptor (BAFF-R, TNFRSF13C) is required for generation and maintenance of mature B cells, but there are no data as to any role for the BAFF/BAFF-R pathway in T cell functions. We report that the binding of BAFF to BAFF-R expressed by a subset of primarily CD4(+) T cells costimulates T cell activation and allo-proliferation in vitro and in vivo, and that mice with a mutation in the BAFF-R, or with a targeted deletion of BAFF, show prolonged cardiac allograft survival as compared to wild-type or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)(-/-) controls. Taken together, these data indicate the BAFF/BAFF-R pathway contributes to both T and B cell responses and may be an attractive target for control of acute and chronic allograft rejection.     

ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease-like cerebral amyloidosis

Epidemiological studies suggest links between cholesterol metabolism and Alzheimer's disease (AD), with hypercholesterolemia associated with increased AD risk, and use of cholesterol-lowering drugs associated with decreased risk. Animal models using cholesterol-modifying dietary or pharmacological interventions demonstrate similar findings. Proposed mechanisms include effects of cholesterol on the metabolism of amyloid-beta (Abeta), the protein that deposits in AD brain. To investigate the effect of genetic alterations in plasma cholesterol on Abeta pathology, we crossed the PDAPP transgenic mouse model of AD-like cerebral amyloidosis to apolipoprotein AI-null mice that have markedly reduced plasma cholesterol levels due to a virtual absence of high density lipoproteins, the primary lipoprotein in mice. Interestingly and in contrast to models using non-physiological high fat diets or cholesterol-lowering drugs to modify plasma cholesterol, we observed no differences in Abeta pathology in PDAPP mice of the various apoAI genotypes despite robust differences in plasma cholesterol levels between the groups. Absence of apoAI also resulted in reductions in brain but not cerebrospinal fluid cholesterol, but had no effect on brain apolipoprotein E levels. These and other data suggest that it is perhaps the level of brain apolipoprotein E, not cholesterol per se, that plays a primary role in brain Abeta metabolism.     

Performance of commercially available enzyme immunoassays for detection of antibodies against herpes simplex virus type 2 in African populations

Data are accumulating on the performance of enzyme immunoassays (EIAs) for the detection of herpes simplex virus type 2 (HSV-2) infection in North America and Europe, but little is known about their performance in other populations. Nine test kits were evaluated with 330 serum samples from sub-Saharan Africa. The tests were first compared to the monoclonal antibody (MAb) EIA (Central Public Health Laboratory, London, United Kingdom). Samples that gave discordant results in the MAb EIA and in the three tests that performed best compared to the MAb EIA were tested by Western blotting (University of Washington, Seattle). A random sample of concordant samples was also tested, and the sensitivities and specificities of the different tests were calculated, taking into account this sampling strategy. The sensitivities of the tests ranged from 86 to 100%; the specificities ranged from 47 to 99%. The tests that performed best were the Gull Premier EIA (sensitivity, 86.3%; specificity, 97.6%) and the Kalon Biological (sensitivity, 92.3%; specificity, 97.7%) and Biokit (sensitivity, 86.7%; specificity, 92.6%) tests. It cannot be assumed that enzyme immunoassays for the detection of HSV-2 infection that perform well in industrialized countries will perform equally well in other populations.     

Linking chronic stress to insomnia symptoms in older adults: The role of stress co-occurrence during the pandemic

Studies examining the associations of chronic stressors with sleep health in older adults have shown conflicting results. While the COVID-19 pandemic increased perceived stress at the population level, less is known about chronic stressors experienced by older adults in the context of the COVID-19 pandemic and its impact on sleep health in an aging population. This study aims to examine the association of older adults' chronic stress with insomnia symptoms during the first year of the COVID-19 pandemic. A cross-sectional analysis was performed using early-release COVID-19 data from the Health and Retirement Study. Data on chronic stressors and insomnia symptoms in older adults (N = 2021; mean age = 68.8) were examined. Co-occurrence network analysis, latent class analysis, Rao–Scott χ² tests, and multivariable logistic regression were used to characterize the co-occurrence of chronic stressors and associations with insomnia symptoms. The most common co-occurring chronic stressors during the first year of the COVID-19 pandemic were self-health issues, family-health issues, and financial stress. Older adults experiencing frequent stress co-occurrence had 91% higher odds of difficulty initiating sleep (p < 0.001), 40% higher odds of frequent nocturnal awakening (p = 0.028), and 83% higher odds of nonrestorative sleep (p < 0.001). However, adjustment for health risk factors and COVID-19 concerns attenuated the effects, leaving strongest association for difficulty initiating sleep (odds ratio = 1.51, p = 0.010). Frequent stress co-occurrence plays an important role linking chronic stress to insomnia symptoms in an aging population. Ongoing research is needed to examine the lingering effects of frequent stress co-occurrence on older adults' sleep health in the post COVID-19 era.     

Diagnostic utility of an age‐specific cut‐off for d‐dimer for pulmonary embolism assessment when used with various pulmonary embolism risk scores

This retrospective cohort study compared the diagnostic utility (sensitivity, specificity and negative predictive value (NPV)) of the age‐times‐10 adjusted d‐dimer cut‐off used in combination with the original and simplified Well's pulmonary embolism (PE) scores and the original and simplified revised Geneva scores to identify patients in whom PE is classified as unlikely according to each score. The PE risk scores performed similarly with high sensitivity (97.6, 97.1, 96.9 and 97.1% respectively) and NPV (99.3, 99.3, 99.2 and 99.2% respectively). Each missed only one PE. The age‐times‐10 age‐adjusted d‐dimer assay cut‐off performed similarly with each of the clinical risk scores tested with high sensitivity and NPV.     

Differential changes in functional disability and pain intensity over the course of psychological treatment for children with chronic pain

Patients presenting for treatment of chronic pain often believe that pain reduction must be achieved before returning to normal functioning. However, treatment programs for chronic pain typically take a rehabilitative approach, emphasizing decreasing pain-related disability first with the expectation that pain reduction will follow. This information is routinely provided to patients, yet no studies have systematically examined the actual trajectories of pain and disability in a clinical care setting. In this study of youth with chronic pain (N = 94, 8 to 18 years), it was hypothesized that 1) functional disability and pain would decrease over the course of psychological treatment for chronic pain and 2) functional disability would decrease more quickly than pain intensity. Participants received cognitive behavioral therapy (CBT) for pain management (M = 5.6 sessions) plus standard medical care. The Functional Disability Inventory and a Numeric Rating Scale of average pain intensity were completed by the child at every CBT session. Hierarchical linear modeling was conducted to examine the longitudinal trajectories of disability and pain. Standardized estimates of the slopes of change were obtained to test differences in rates of change between pain and disability. Results showed an overall significant decline in functional disability over time. Although pain scores reduced slightly from pretreatment to posttreatment, the longitudinal decline over treatment was not statistically significant. As expected, the rate of change of disability was significantly more rapid than pain. Evidence for variability in treatment response was noted, suggesting the need for additional research into individual trajectories of change in pediatric pain treatment.