Changes in Sleep Disruption in the Treatment of Co‐Occurring Posttraumatic Stress Disorder and Substance Use Disorders

Sleep disruption appears not only to reflect a symptom of posttraumatic stress disorder (PTSD), but also a unique vulnerability for its development and maintenance. Studies examining the impact of psychosocial treatments for PTSD on sleep symptoms are few and no studies to date of which we are aware have examined this question in samples with co‐occurring substance use disorders. The current study is a secondary analysis of a large clinical trial comparing 2 psychological treatments for co‐occurring PTSD and substance use disorders. Women (N = 353) completed measures of PTSD at baseline, end of treatment, and 3‐, 6‐, and 12‐month follow‐ups. Results indicated that the prevalence of insomnia, but not nightmares, decreased during treatment, and that 63.8% of participants reported at least 1 clinical‐level sleep symptom at the end of treatment. Improvement in sleep symptoms during treatment was associated with better overall PTSD outcomes over time, χ²(1) = 33.81, p < .001. These results extend the existing literature to suggest that residual sleep disruption following PTSD treatment is common in women with co‐occurring PTSD and substance use disorders. Research on the benefits of adding sleep‐specific intervention for those with residual sleep disruption in this population may be a promising future direction.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis (sALS)

The aim of this study was to identify gene expression profiles in peripheral blood mononuclear cells (PBMCs) from sporadic amyotrophic lateral sclerosis (sALS) patients to gain insights into the pathogenesis of ALS. We found that upregulation of LPS/TLR4-signaling associated genes was observed in the PMBCs from sALS patients after short-term cultivation, and that elevated levels of gene expression correlated with degree of peripheral blood monocyte activation and plasma LPS levels in sALS. Similar patterns of gene expression were reproduced in LPS stimulated PBMCs from healthy controls. These data suggest that chronic monocyte/macrophage activation may be through LPS/TLR4-signaling pathways in ALS.     

Promising treatments for women with comorbid PTSD and substance use disorders

OBJECTIVE: The authors' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder (PTSD) and substance abuse (seeking safety) with a manualized cognitive behavior therapy that addresses only substance abuse (relapse prevention) and with standard community care for the treatment of comorbid posttraumatic stress disorder (PTSD) and substance use disorder. METHOD: One hundred seven women from an urban, low-income population who had comorbid PTSD and substance use disorder were randomly assigned to receive the two kinds of cognitive behavior therapy or received standard community treatment. Participants were recruited from both community and clinical populations and evaluated with structured clinical instruments. Forty-one women received seeking safety therapy, 34 received relapse prevention therapy, and 32 received standard community care. RESULTS: At the end of 3 months of treatment, participants in both cognitive behavior therapy conditions had significant reductions in substance use, PTSD, and psychiatric symptoms, but community care participants worsened over time. Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group. CONCLUSIONS: Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD, substance use disorder, and other psychiatric symptoms.     

Heart transplantation: echocardiographic assessment of morphology and function after more than 10 years of follow-up

BACKGROUND: Over recent years, heart transplantation (HTX) developed into a successful option for long-term treatment of end-stage heart failure. Ten-year survival ranges between 40% and 50%. Little is known, however, about function and morphology of transplanted hearts during follow-up of more than 10 years. METHODS: In a consecutive cohort of 65 patients (55 male, 54.6 +/- 12.1 years at the time of transplantation), graft function was assessed by color Doppler echocardiography 12.5 +/- 1.4 years after heart transplantation (10 to 15 years). RESULTS: Left atrial and ventricular dimensions were found in a normal range (LA 37.7 +/- 8.9 mm, LV enddiastolic 45.6 +/- 6.4 mm, 30 to 71 mm). Ejection fraction (EF) of 71 +/- 11.7% and a fractional shortening of 35.3 +/- 10.3% presented with normal values. Left ventricular mass (male 263.8 +/- 111.4 g, female 373.0 +/- 181.1 g) was slightly increased resulting in mild hypertrophy in women. Focused on right ventricular morphology, enlargement of both the right atrium and the right ventricle (RA 40.7 +/- 11.8 mm, RV 37.4 +/- 8.3 mm) was observed in the majority of the patients. Tricuspid valve insufficiency (> grade II) was present in 46 of 65 patients; 5 patients had previously undergone tricuspid valve replacement. Atrial filling waves were detectable in only 47 of 65 patients, thus, 28% of patients showed signs of LA-dysfunction. CONCLUSIONS: More than 10 years post-HTX, cardiac grafts were characterized by normal left ventricular dimensions and ejection fraction. LA-dysfunction and RV-enlargement associated with tricuspid insufficiency were frequent findings, however, not associated with clinical signs of congestive heart failure in the majority of patients.     

Assessment of the factors associated with flavivirus seroprevalence in a population in Southern Vietnam

Dengue and Japanese encephalitis flaviviruses cause severe disease and are hyperendemic in southern Vietnam. This study assesses associations between sociodemographic factors and flavivirus seroprevalence in this region. Sera were collected from 308 community and hospital-based subjects between April 1996 and August 1997 and tested with an indirect ELISA. The factors associated with seroprevalence were assessed using multivariate logistic regression. In this first report of adjusted prevalence odds ratios (POR) for flavivirus infection in Vietnam, seropositivity was associated with increasing age in children (multiple regression coefficients for a child compared to an adult = -4.975 and for age in children = 0.354) and residence in the city compared to surrounding rural districts. The association with age indicates that subjects were most likely to have acquired infection in early childhood. This is key to the design of Vietnamese health education and immunization programmes.