Comparing the Costs and Acceptability of Three Fidelity Assessment Methods for Assertive Community Treatment

Successful implementation of evidence-based practices requires valid, yet practical fidelity monitoring. This study compared the costs and acceptability of three fidelity assessment methods: on-site, phone, and expert-scored self-report. Thirty-two randomly selected VA mental health intensive case management teams completed all fidelity assessments using a standardized scale and provided feedback on each. Personnel and travel costs across the three methods were compared for statistical differences. Both phone and expert-scored self-report methods demonstrated significantly lower costs than on-site assessments, even when excluding travel costs. However, participants preferred on-site assessments. Remote fidelity assessments hold promise in monitoring large scale program fidelity with limited resources

Comparison of Assertive Community Treatment Fidelity Assessment Methods: Reliability and Validity

Assertive community treatment is known for improving consumer outcomes, but is difficult to implement. On-site fidelity measurement can help ensure model adherence, but is costly in large systems. This study compared reliability and validity of three methods of fidelity assessment (on-site, phone-administered, and expert-scored self-report) using a stratified random sample of 32 mental health intensive case management teams from the Department of Veterans Affairs. Overall, phone, and to a lesser extent, expert-scored self-report fidelity assessments compared favorably to on-site methods in inter-rater reliability and concurrent validity. If used appropriately, these alternative protocols hold promise in monitoring large-scale program fidelity with limited resources

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-β Associated Neurodegenerative Pathways and Glial Signatures in a Mouse Model of Alzheimer’s Disease: A Targeted Transcriptome Analysis

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, it remains unclear how Arg1 deficiency in these cells impacts the whole brain to promote amyloidosis. Herein, we aim to determine how Arg1 deficiency driven by LysM restriction during amyloidosis affects fundamental neurodegenerative pathways at the transcriptome level. By applying several bioinformatic tools and analyses, we found that amyloid-β (Aβ) stimulated transcriptomic signatures in autophagy-related pathways and myeloid cells’ inflammatory response. At the same time, myeloid Arg1 deficiency during amyloidosis promoted gene signatures of lipid metabolism, myelination, and migration of myeloid cells. Focusing on Aβ associated glial transcriptomic signatures, we found myeloid Arg1 deficiency up-regulated glial gene transcripts that positively correlated with Aβ plaque burden. We also observed that Aβ preferentially activated disease-associated microglial signatures to increase phagocytic response, whereas myeloid Arg1 deficiency selectively promoted homeostatic microglial signature that is non-phagocytic. These transcriptomic findings suggest a critical role for proper Arg1 function during normal and pathological challenges associated with amyloidosis. Furthermore, understanding pathways that govern Arg1 metabolism may provide new therapeutic opportunities to rebalance immune function and improve microglia/macrophage fitness

Arginase 1 Insufficiency Precipitates Amyloid-\u3cem\u3eβ\u3c/em\u3e Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1fl/fl and LysMcreTg/+ mice crossed with APP Tg2576 mice. Our data indicated that Arg1 haploinsufficiency promoted Aβ deposition, exacerbated some behavioral impairment, and decreased components of Ragulator-Rag complex involved in mechanistic target of rapamycin complex 1 (mTORC1) signaling and autophagy. Additionally, Arg1 repression and arginine supplementation both impaired microglial phagocytosis in vitro. These data suggest that proper function of Arg1 and arginine metabolism in myeloid cells remains essential to restrict amyloidosis

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1a) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein crosslinking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1a activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema

Human Rights and German Intellectual History in Transnational Perspective

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156446/1/gequ12147.pd

Goals and regulations of religiosity: A motivational analysis

The fields of religious and motivation psychology have quite independently developed their own conceptualizations and research agendas. Few schol-ars, however, have examined issues that are at the intersection of both fields and, if so, most researchers in the psychology of religion did not make use of existing general motivational frameworks to enrich their understanding of the motivational dynamics for religious behaviors. The aim of the present chapter is to indicate how self-determination theory (Ryan & Deci, (2000a) American Psychologist, 55, 68–78) might help to further refine Allport’s classical distinction between intrinsic and extrinsic religious orientation. Specifically, it is argued that the reasons or reg-ulations for religious behavior (initially, intrinsic vs. extrinsic; later, au-tonomous vs. controlled) and the goals of religious behavior (intrinsic vs. extrinsic), as they are defined within self-determination theory, are not distinguished within Allport’s and other researchers ’ frameworks. Both conceptual dimensions might better be disentangled, so that their inde-pendent effects could be studied. 1