Neuroimaging and Cognitive Outcomes in Adults with Human Immunodeficiency Virus and Early Life Stress

Brain abnormalities persist in individuals with human immunodeficiency virus (HIV) despite the use of highly active antiretroviral therapy (HAART). To date, limited work has focused on the association between early life stress (ELS) and brain integrity in individuals with HIV, although ELS is highly prevalent in this population. The present study was conducted to determine whether ELS corresponds to the expression of persistent HIV–related neuroimaging abnormalities and cognitive dysfunction. A total of 130 HIV+ individuals on HAART and 76 HIV– individuals underwent 3T structural magnetic resonance imaging, diffusion tensor imaging, and neuropsychological assessment. Individuals were free of major psychiatric illness and neurological confounds. Participants were stratified into high or low ELS groups based on self-reported exposure to early life adversity using the Early Life Stress Questionnaire (ELSQ). No significant interactions were observed between HIV serostatus and ELS on white matter microstructural integrity, brain volumes, or cognition. However, HIV+ individuals exhibited significantly greater whole-brain white matter microstructural abnormalities, smaller brain volumes, and worse cognition compared to the HIV– group. Collapsed across HIV serostatus, individuals with high ELS demonstrated more severe whole-brain white matter microstructural abnormalities compared to individuals with low ELS. Results of present study suggest that high ELS is not a primary contributor to the neuropathogenic model of HIV in HAART-treated individuals. Evidence of persistent brain abnormalities among treated HIV+ individuals is consistent with results from other studies, further emphasizing the need to monitor cognitive health in patients after sustained HIV treatment

Physical activity affects brain integrity in HIV+ individuals

Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV−) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV +) individuals. Seventy HIV + individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV + individuals were classified as physically active (any energy expended above resting expenditure, n = 22) or sedentary (n = 48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV + individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p = .034). Physically active HIV + individuals performed better on executive (p = .040, unadjusted; p = .043, adjusted) but not motor function (p = .17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r = 0.45, p = 0.035) but not motor (r = 0.21; p = .35) performance. In adjusted analyses the physically active HIV + individuals had larger putamen volumes (p = .019). A positive relationship exists between PA and brain integrity in HIV + individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV + individuals

Application of a Novel Quantitative Tractography Based Analysis of Diffusion Tensor Imaging to Examine Fiber Bundle Length in Human Cerebral White Matter

This paper reviews basic methods and recent applications of length-based fiber bundle analysis of cerebral white matter using diffusion magnetic resonance imaging (dMRI). Diffusion weighted imaging (DWI) is a dMRI technique that uses the random motion of water to probe tissue microstructure in the brain. Diffusion tensor imaging (DTI) is an extension of DWI that measures the magnitude and direction of water diffusion in cerebral white matter, using either voxel-based scalar metrics or tractography-based analyses. More recently, quantitative tractography based on diffusion tensor imaging (qtDTI) technology has been developed to help quantify aggregate structural anatomical properties of white matter fiber bundles, including both scalar metrics of bundle diffusion and more complex morphometric properties, such as fiber bundle length (FBL). Unlike traditional scalar diffusion metrics, FBL reflects the direction and curvature of white matter pathways coursing through the brain and is sensitive to changes within the entire tractography model. In this paper, we discuss applications of this approach to date that have provided new insights into brain organization and function. We also discuss opportunities for improving the methodology through more complex anatomical models and potential areas of new application for qtDTI

Topological organization of whole-brain white matter in HIV infection

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T(1)-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance

P2Y2 receptors Transactivate the EGFR/ERB1 and ERB3 Growth Factor Receptors in Human Salivary Gland Cells [abstract]

Abstract only availableThe epidermal growth factor receptor (EGFR/ERB1) plays a key role in the regulation of epithelial cell development, differentiation and in the pathophysiology of hyperproliferative diseases such as cancer. Transactivation of the EGFR/ERB1 by G-protein coupled receptors has been shown to be dependent on proteolytic cleavage of membrane ligands such as heparin binding epidermal growth factor (HBEGF), EGF, transforming growth factor (TGF-), epiregulin, amphiregulin and betacellulin. Utilizing the human submandibular gland (HSG) cell line, we found that activation of the P2Y2 nucleotide receptor (P2Y2R) by its agonist UTP caused a time-dependent activation of EGFR/ERB1; however, neutralizing antibodies to the known ligands to EGFR/ERB1 failed to inhibit the UTP-induced phosphorylation of EGFR/ERB1. EGFR/ERB1 phosphorylation can also be induced by heterodimerization with one of the other ERB family members, ERB2, ERB3, and ERB4. HSG cells express ERB2 and ERB3 but not ERB4. Since ERB2 is a ligandless receptor, ERB3 is the likely dimerizing partner. Our results indicate that P2Y2R activation by UTP phosphorylates ERB3. Heregulin, the only known ligand for ERB3 is expressed in HSGs. Therefore, our results suggest that P2Y2R activation stimulates the formation of ERB3-EGFR/ERB1 heterodimers by cleavage of heregulin and its binding to ERB3

Long-Term Conditions Questionnaire (LTCQ): initial validation survey among primary care patients and social care recipients in England

Objective: The aim of this study was to validate a new generic patient-reported outcome measure, the Long-Term Conditions Questionnaire (LTCQ), among a diverse sample of health and social care users in England. Design: Cross-sectional validation survey. Data were collected through postal surveys (February 2016 - January 2017). The sample included a health care cohort of patients recruited through primary care practices, and a social care cohort recruited through local government bodies that provide social care services. Participants: 1,211 participants (24% confirmed social care recipients) took part in the study. Health care participants were recruited on the basis of having one of eleven specified LTCs, and social care participants were recruited on the basis of receiving social care support for at least one LTC. The sample exhibited high multi-morbidity, with 93% reporting two or more LTCs and 43% reporting a mental health condition. Outcome measures: The LTCQ’s construct validity was tested with reference to the EQ-5D (5-level version), the Self-efficacy for Managing Chronic Disease scale, an Activities of Daily Living scale, and the Bayliss burden of morbidity scale. Results: Low levels of missing data for each item indicate acceptability of the LTCQ across the sample. The LTCQ exhibits high internal consistency (Cronbach’s α = 0.95) across the scale’s 20 items and excellent test-retest reliability (ICC = 0.94, 95% CI 0.93 to 0.95). Associations between the LTCQ and all reference measures were moderate to strong and in the expected directions, indicating convergent construct validity. Conclusions: This study provides evidence for the reliability and validity of the Long-Term Conditions Questionnaire, which has potential for use in both health and social care settings. The LTCQ could meet a need for holistic outcome measurement that goes beyond symptoms and physical function, complementing existing measures to fully capture what it means to live well with LTCs

Establishing an implementation network: lessons learned from community-based participatory research

<p>Abstract</p> <p>Background</p> <p>Implementation of evidence-based mental health assessment and intervention in community public health practice is a high priority for multiple stakeholders. Academic-community partnerships can assist in the implementation of efficacious treatments in community settings; yet, little is known about the processes by which these collaborations are developed. In this paper, we discuss our application of community-based participatory research (CBPR) approach to implementation, and we present six lessons we have learned from the establishment of an academic-community partnership.</p> <p>Methods</p> <p>With older adults with psychosis as a focus, we have developed a partnership between a university research center and a public mental health service system based on CBPR. The long-term goal of the partnership is to collaboratively establish an evidence-based implementation network that is sustainable within the public mental healthcare system.</p> <p>Results</p> <p>In building a sustainable partnership, we found that the following lessons were instrumental: changing attitudes; sharing staff; expecting obstacles and formalizing solutions; monitoring and evaluating; adapting and adjusting; and taking advantage of emerging opportunities. Some of these lessons were previously known principles that were modified as the result of the CBPR process, while some lessons derived directly from the interactive process of forming the partnership.</p> <p>Conclusion</p> <p>The process of forming of academic-public partnerships is challenging and time consuming, yet crucial for the development and implementation of state-of-the-art approaches to assessment and interventions to improve the functioning and quality of life for persons with serious mental illnesses. These partnerships provide necessary organizational support to facilitate the implementation of clinical research findings in community practice benefiting consumers, researchers, and providers.</p