Attachment style and coping in relation to posttraumatic stress disorder symptoms among adults living with HIV/AIDS

Research indicates that a significant proportion of people living with HIV/AIDS report symptoms of posttraumatic stress disorder (PTSD). Moreover, attachment style has been associated with psychological and behavioral outcomes among persons living with HIV/AIDS. Attachment style may influence the ability to cope with traumatic stress and affect PTSD symptoms. To examine the association between attachment style and coping with PTSD symptoms, we assessed 94 HIV-positive adults on self-report measures of posttraumatic stress, coping, and attachment style. In multiple regression analysis, avoidant attachment and emotion-focused coping were positively and significantly associated with greater PTSD symptomatology. Support was also found for the moderating effects of avoidant and insecure attachment styles on emotion-focused coping in relation to greater PTSD symptoms. Taken altogether, these results suggest that interventions that develop adaptive coping skills and focus on the underlying construct of attachment may be particularly effective in reducing trauma-related symptoms in adults living with HIV/AIDS.     

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with ¹¹C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.     

Effects of aging on neural connectivity underlying selective memory for emotional scenes

Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults' encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults' connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item.     

The differential dependence of abstract and concrete words upon associative and similarity-based information: Complementary semantic interference and facilitation effects

We report mirror-image effects of interference and facilitation in the semantic processing of identical sets of abstract and concrete words in a patient F.B.I. with global aphasia following a large left middle cerebral artery stroke. Interference was elicited when the tasks involved comprehending the spoken form of each word, but facilitation was found when the patient read aloud the written forms of the same words. More importantly, irrespective of whether the dynamic effect was one of facilitation or interference, effects of semantic association were observed for abstract words, whilst effects primarily of semantic similarity were observed for concrete words. These results offer further neuropsychological evidence that the more abstract a word, the greater its dependence upon associative information and the smaller its dependence upon similarity-based information. The investigations also contribute to a converging body of evidence that suggests that this theory generalizes across different experimental paradigms, stimuli, and participants and also across different cognitive processes within individual patients. The data support a graded rather than binary or ungraded model of the relationships between concreteness, association, and similarity, and the basis for concrete words’ greater dependence upon similarity-based information is discussed in terms of the development of taxonomic structures and categorical thought in young children.     

FAK inhibition decreases cell invasion, migration and metastasis in MYCN amplified neuroblastoma

Neuroblastoma, the most common extracranial solid tumor of childhood, is responsible for over 15 % of pediatric cancer deaths. We have shown that neuroblastoma cell lines overexpress focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase that controls a number of tumorigenic pathways. In this study, we hypothesized that inhibition of FAK would result in decreased cellular migration and invasion in neuroblastoma cell lines, and decrease metastasis in a murine model. We utilized non-isogenic and isogenic MYCN human neuroblastoma cell lines and parallel methods of FAK inhibition. Cell viability, migration, and invasion assays were employed to assess the effects of FAK inhibition in vitro. A nude mouse model was utilized to determine the effects of FAK inhibition on in vivo liver metastasis. FAK knockdown with siRNA resulted in decreased invasion and migration in neuroblastoma cell lines, and the effects of siRNA-induced FAK inhibition were more pronounced in MYCN amplified cell lines. In addition, abrogation of FAK with a small molecule inhibitors resulted in decreased cell survival, migration and invasion in neuroblastoma cell lines, again most pronounced in cell lines with MYCN amplification. Finally, small molecule FAK inhibition in a nude mouse model resulted in a significant decrease in metastatic tumor burden in SK-N-BE(2) injected animals. We believe that FAK plays an important role in maintaining and propagating the metastatic phenotype of neuroblastoma cells, and this driver role is exaggerated in cell lines that overexpress MYCN. FAK inhibition warrants further investigation as a potential therapeutic target in the treatment of aggressive neuroblastoma.     

Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood–brain barrier during extravasation and brain invasion

It is not yet known how tumour cells traverse the blood–brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p < 0.05) and SP immunoreactivity (p < 0.01) and significantly reduced endothelial barrier antigen labelling of microvessels when compared to culture medium control animals (p < 0.001). By day 9 after tumour cell inoculation, 100 % of animals developed large intracranial neoplasms that had significantly increased albumin in the peri-tumoral area (p < 0.001). The increased SP immunoreactivity and altered BBB properties at 3 days post-inoculation that coincided with early tumour invasion may be indicative of a mechanism for tumour cell extravasation into the brain. Thus, extravasation of tumour cells into the brain to form cerebral metastases may be a SP-mediated process.