Erythroid-Specific Transcriptional Changes in PBMCs from Pulmonary Hypertension Patients

Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression

Structural brain correlates of childhood inhibited temperament: an ENIGMA-Anxiety Mega-analysis

NWORubicon 019.201SG.022Pathways through Adolescenc

Promotion of Healthy Humor Cancer Education Messages for the Deaf Community.

The Deaf community members of this community-campus partnership identified the lack of health information in American Sign Language (ASL) as a significant barrier to increasing the Deaf community's health knowledge. Studies have shown that the delivery of health messages in ASL increased Deaf study participants' cancer knowledge. Once health messages are available on the Internet, strategies are needed to attract viewers to the website and to make repeat visits in order to promote widespread knowledge gains. This feasibility study used the entertainment-education strategy of coupling cancer information with jokes in ASL to increase the appeal and impact of the health messages. ASL-delivered cancer control messages coupled with Deaf-friendly jokes were shown to 62 Deaf participants. Participants completed knowledge questionnaires before, immediately after, and 1 week after viewing the paired videos. Participants' health knowledge statistically significantly increased after viewing the paired videos and the gain was retained 1 week later. Participants also reported sharing the newly acquired information with others. Statistically significant results were demonstrated across nearly all measures, including a sustained increase in cancer-information-seeking behavior and intent to improve health habits. Most participants reported that they would be motivated to return to such a website and refer others to it, provided that it was regularly updated with new jokes

Psychometric Evaluation of the Patient Health Questionnaire-4 in Hispanic Americans.

The present study evaluated the psychometric properties of the Patient Health Questionnaire-4 (PHQ-4), a screener of psychological distress, in English- and Spanish-speaking Hispanic Americans. Hispanic American adults (N = 436) completed the PHQ-4, which yields two subscales (anxiety and depression) that can be summed to create a total score. Multiple-group confirmatory factor analysis was used to evaluate structural validity. The two-factor structure was the best fit to the data for both English- and Spanish-speaking Hispanic Americans and items loaded equivalently across groups, demonstrating measurement invariance. Internal consistency reliability was good as measured by coefficient alpha. Construct validity was evidenced by significant expected relationships with perceived stress. These findings provide support for the reliability and validity of the PHQ-4 as a brief measure of psychological distress for English- or Spanish-speaking Hispanic Americans

The Psychometric Properties of English and Spanish Versions of the Life Orientation Test-Revised in Hispanic Americans

The Life Orientation Test-Revised (LOT-R) is a widely used measure of optimism and pessimism, with three positively worded and three negatively worded content items. This study examined the structural validity and invariance, internal consistency reliability, and convergent and divergent validity of the English and Spanish versions of the LOT-R among Hispanic Americans. A community sample of Hispanic Americans (N = 422) completed self-report measures, including the LOT-R, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, in their preferred language of English or Spanish. Based on the literature, four structural models were tested: one-factor, oblique two-factor, orthogonal two-factor method effects with positive specific factor, and orthogonal two-factor method effects with negative specific factor. Baseline support for both of the English and Spanish versions was not achieved for any model; in all models, the negatively worded items in Spanish had non-significant factor loadings. Therefore, the positively worded three-item optimism subscale of the LOT-R was examined separately and fit the data, with factor loadings equivalent across language-preference groups. Coefficient alphas for the optimism subscale were consistent across both language-preference groups (αs = .61 [English] and .66 [Spanish]). In contrast, the six-item total score and three-item pessimism subscale demonstrated extremely low or inconsistent alphas. Convergent and divergent validity were established for the optimism subscale in both languages. In sum, the optimism subscale of the LOT-R demonstrated minimally acceptable to good psychometric properties across English and Spanish language-preference groups. However, neither the total score nor the pessimism subscale showed adequate psychometric properties for Spanish-speaking Hispanic Americans, likely due to translation and cultural adaptation issues, and thus are not supported for use with this population

The Psychometric Properties of English and Spanish Versions of the Life Orientation Test-Revised in Hispanic Americans.

The Life Orientation Test-Revised (LOT-R) is a widely used measure of optimism and pessimism, with three positively worded and three negatively worded content items. This study examined the structural validity and invariance, internal consistency reliability, and convergent and divergent validity of the English and Spanish versions of the LOT-R among Hispanic Americans. A community sample of Hispanic Americans (N = 422) completed self-report measures, including the LOT-R, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, in their preferred language of English or Spanish. Based on the literature, four structural models were tested: one-factor, oblique two-factor, orthogonal two-factor method effects with positive specific factor, and orthogonal two-factor method effects with negative specific factor. Baseline support for both of the English and Spanish versions was not achieved for any model; in all models, the negatively worded items in Spanish had non-significant factor loadings. Therefore, the positively worded three-item optimism subscale of the LOT-R was examined separately and fit the data, with factor loadings equivalent across language-preference groups. Coefficient alphas for the optimism subscale were consistent across both language-preference groups (αs = .61 [English] and .66 [Spanish]). In contrast, the six-item total score and three-item pessimism subscale demonstrated extremely low or inconsistent alphas. Convergent and divergent validity were established for the optimism subscale in both languages. In sum, the optimism subscale of the LOT-R demonstrated minimally acceptable to good psychometric properties across English and Spanish language-preference groups. However, neither the total score nor the pessimism subscale showed adequate psychometric properties for Spanish-speaking Hispanic Americans, likely due to translation and cultural adaptation issues, and thus are not supported for use with this population

Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer

Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy