Classification of performance validity and symptom validity using the Trauma Symptom Inventory-2.

The Trauma Symptom Inventory-Second Edition (TSI-2) is garnering research interest as a symptom validity test in the evaluation of trauma-related disorders. However, there has been limited empirical validation of its validity scales in clinical and forensic real-world settings. This study evaluated the ability of the TSI-2 Atypical Response (ATR) scale to discriminate response bias in cognitive performance and symptom reporting in a large sample of disability and compensation-seeking claimants. This retrospective chart review included 296 adults with a known history of trauma exposure or claimed trauma-related psychological injury who underwent neuropsychological and/or comprehensive psychological assessment in a private neuropsychology clinic. The discriminability of the ATR scale to classify credible versus non-credible cognitive profiles and symptom reporting were analyzed by AUC-ROCs. Overall, the ATR scale demonstrated poor discriminability of assessment validity based on the Word Memory Test, Victoria Symptom Validity Test, and Minnesota Multiphasic Personality Inventory-2-Restructured Form. The ATR scale had fair discriminatory ability of only one of the over-reporting scales (F-r), with an ROC area of .73, p = .001. However, the test publisher's proposed ATR cut-offs of ≥8 for screening, research, and normal groups, and ≥15 in forensic and clinical settings revealed significant issues with sensitivity and specificity. These results suggest that the TSI-2 should be paired with other established performance validity and symptom validity tests in clinical assessments and not be used as the primary or sole indicator of assessment validity.

[Short version of a quality-of-life questionnaire in primary caregivers of children with atopic dermatitis (QPCAD): development and validation of QP9].

BACKGROUND: QPCAD (Quality of life in Primary Caregivers of children with Atopic Dermatitis) is a questionnaire with 19 items, which was developed to evaluate the QOL of primary caregivers of children with atopic dermatitis (AD). We developed an abbreviated version of QPCAD (QP9) to reduce the burden of respondents and to popularize the evaluation of QOL in clinical practice, and evaluated its reliability, validity, and responsiveness. METHODS: We applied factor analysis to the data of primary caregivers of AD children at the age of 0 to 6, tried to select the items of QP9. Next, we evaluated the reliability of QP9 based on the data of reliability analysis set of caregivers. We also examined the associations of scores of QP9 with background characteristics and the AD severity index for the validity analysis. In addition, we examined associations of the amount of change of scores with that of the AD severity index for the responsiveness analysis. RESULTS: We selected the items of QP9 consisting of 9 items based on the data of 529 primary caregivers. We confirmed sufficient reliability of the item scores. We found the expected associations between the scores and background characteristics and AD severity. We also found the association between the amount of change of pre- and post-treatment scores and that of the AD severity. CONCLUSIONS: QP9 must be a useful questionnaire with sufficient reliability, validity, and responsiveness, as a QOL scale of primary caregivers of AD children.

Increased leukotriene E4 in the exhaled breath condensate of children with mild asthma.

BACKGROUND: Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels. METHODS: We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination. RESULTS: Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012). CONCLUSION: EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.

Phosphoinositide 3-kinase cascade facilitates mu-opioid desensitization in sensory neurons by altering G-protein-effector interactions.

Signaling via G-protein-coupled receptors undergoes desensitization after prolonged agonist exposure. Here we investigated the role of phosphoinositide 3-kinase (PI3K) and its downstream pathways in desensitization of micro-opioid inhibition of neuronal Ca2+ channels. In cultured mouse dorsal root ganglion neurons, two mechanistically different forms of desensitization were observed after acute or chronic treatment with the micro agonist [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin (DAMGO). Chronic DAMGO desensitization was heterologous in nature and significantly attenuated by blocking the activity of PI3K or mitogen-activated protein kinase (MAPK). A combined application of PI3K and MAPK inhibitors showed no additive effect, suggesting that these two kinases act in a common pathway to facilitate chronic desensitization. Acute DAMGO desensitization, however, was not affected by the inhibitors. Furthermore, upregulation of the PI3K-Akt pathway in mutant mice lacking phosphatase and tensin homolog, a lipid phosphatase counteracting PI3K, selectively enhanced chronic desensitization in a PI3K- and MAPK-dependent manner. Using the prepulse facilitation (PPF) test, we further examined changes in the voltage-dependent component of DAMGO action that requires direct interactions between betagamma subunits of G-proteins and Ca2+ channels. DAMGO-induced PPF was diminished after chronic treatment, suggesting disruption of G-protein-channel interactions. Such disruption could occur at the postreceptor level, because chronic DAMGO also reduced GTPgammaS-induced PPF that was independent of receptor activation. Again, inhibition of PI3K or MAPK reduced desensitization of PPF. Our data suggest that the PI3Kcascade involving MAPK and Akt enhances micro-opioid desensitization via postreceptor modifications that interfere with G-protein-effector interactions.

Apolipoprotein E enhances uptake of soluble but not aggregated amyloid-beta protein into synaptic terminals.

The cellular mechanism by which apolipoprotein E (apoE) affects the pathogenesis of Alzheimer's disease (AD) is not understood. We have examined the effect of apolipoprotein E on the internalization of exogenous amyloid-beta 1-40 (Abeta40) into a rat brain crude synaptosomal preparation. Abeta40 peptide in soluble (within 1 h of dilution in buffer) or aggregated (aged 4 days before dilution in buffer) form was pre-incubated with lipidated apoE then added to synaptosomes; intraterminal amyloid-beta labeling was quantified using flow cytometry following immunolabeling with the anti-Abeta (10G4) antibody. The number of Abeta-positive synaptosomes was increased ( approximately 50%) by treatment with a soluble Abeta/apoE mixture compared with treatment with soluble Abeta40 alone. However, when the Abeta was aggregated, less sodium dodecyl sulfate (SDS)-stable Abeta/apoE complex was formed and the addition of apoE decreased the number of Abeta-positive terminals. The addition of the lipoprotein-receptor related protein (LRP) antagonist receptor-associated protein (RAP) inhibited the apoE-induced increase in synaptosomal Abeta, and controls treated with trypsin and heparinase confirm intraterminal localization of the majority of the soluble Abeta. The apoE-mediated increase in Abeta labeling was confirmed in intact cells by immunocytochemistry of dorsal root ganglion (DRG) neurons. These results suggest that complex formation with apoE enhances internalization of soluble Abeta uptake into terminals.

Rat ventral midbrain dopamine neurons express the orphanin FQ/nociceptin receptor ORL-1.

Orphanin FQ/nociceptin, (OFQ/N) the endogenous ligand for the ORL-1 receptor, has been shown previously to modulate extracellular dopamine concentration in the nucleus accumbens following both intracerebroventricular and intra-ventral tegmental area administration. However, it is unclear whether or not this is a result of a direct action of OFQ/N on ORL-1 receptors located on dopamine neurons. We sought evidence for expression of the ORL-1 receptor in dopamine cells located in the ventral tegmental area and substantia nigra of the rat brain using double-label in situ hybridization. Within the ventral tegmental area, 91% of tyrosine hydroxylase-positive cells were also positive for ORL-1 hybridization. Similarly, in the substantia nigra 90% of tyrosine hydroxylase-positive cells in the zona compacta expressed ORL-1 message and 84% of tyrosine hydroxylase-positive cells in the zona reticulata colocalized ORL-1 message. These data provide the anatomical basis for a direct modulatory effect of OFQ/N on mid-brain dopamine neurons.