Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aß) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aß is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e., microglia), which culminates in neuronal damage and cognitive decline. To test this hypothesis, many in vitro systems have been established to study Aß-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. METHODS: We used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic Aß or LPS and INFγ. RESULTS: We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic Aß does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of Aß formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INFγ activate microglia and induce transcriptional changes that resemble many, but not all, aspects of the transcriptomic profiles of disease associated microglia (DAM) present in the AD brain. CONCLUSIONS: These results suggest that synthetic Aß treatment of innate immune cell cultures does not recapitulate transcriptional profiles observed in microglia from AD brains. In contrast, treating IMGL with LPS and INFγ induces transcriptional changes similar to those observed in microglia detected in AD brains.

Transcriptional response of human articular chondrocytes treated with fibronectin fragments: an in vitro model of the osteoarthritis phenotype.

OBJECTIVE: Fibronectin is a matrix protein that is fragmented during cartilage degradation in osteoarthritis (OA). Treatment of chondrocytes with fibronectin fragments (FN-f) has been used to model OA in vitro, but the system has not been fully characterized. This study sought to define the transcriptional response of chondrocytes to FN-f, and directly compare it to responses traditionally observed in OA. DESIGN: Normal human femoral chondrocytes isolated from tissue donors were treated with either FN-f or PBS (control) for 3, 6, or 18 h. RNA-seq libraries were compared between time-matched FN-f and control samples in order to identify changes in gene expression over time. Differentially expressed genes were compared to a published OA gene set and used for pathway, transcription factor motif, and kinome analysis. RESULTS: FN-f treatment resulted in 3,914 differentially expressed genes over the time course. Genes that are up- or downregulated in OA were significantly up- (P < 0.00001) or downregulated (P < 0.0004) in response to FN-f. Early response genes were involved in proinflammatory pathways, whereas many late response genes were involved in ferroptosis. The promoters of upregulated genes were enriched for NF-κB, AP-1, and IRF motifs. Highly upregulated kinases included CAMK1G, IRAK2, and the uncharacterized kinase DYRK3, while growth factor receptors TGFBR2 and FGFR2 were downregulated. CONCLUSIONS: FN-f treatment of normal human articular chondrocytes recapitulated many key aspects of the OA chondrocyte phenotype. This in vitro model is promising for future OA studies, especially considering its compatibility with genomics and genome-editing techniques.

Race-ethnicity and poverty after spinal cord injury.

STUDY DESIGN: Secondary analysis of existing data. OBJECTIVE: Our objective was to examine the relationship between race-ethnicity and poverty status after spinal cord injury (SCI). SETTING: A large specialty hospital in the southeastern United States. METHODS: Participants were 2043 adults with traumatic SCI in the US. Poverty status was measured using criteria from the US Census Bureau. RESULTS: Whereas only 14% of non-Hispanic White participants were below the poverty level, 41.3% of non-Hispanic Blacks were in poverty. Logistic regression with three different models identified several significant predictors of poverty, including marital status, years of education, level of education, age and employment status. Non-Hispanic Blacks had 2.75 greater odds of living in poverty after controlling for other factors, including education and employment. CONCLUSION: We may need to consider quality of education and employment to better understand the elevated risk of poverty among non-Hispanic Blacks in the US.

Barriers and facilitators to employment after spinal cord injury: underlying dimensions and their relationship to labor force participation.

STUDY DESIGN: Cross-sectional survey. OBJECTIVE: To identify barriers and facilitators to employment after spinal cord injury (SCI) and their relationship with labor force participation. METHODS: Participants were initially identified through specialty hospitals in the Midwest and Southeastern United States of America. 781 adults with traumatic SCI, at least 1 year post-injury, and between the ages of 18-64, participated. A 30-item instrument on barriers and facilitators to employment was administered. Analyses included exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and comparisons of scores as a function of employment status. RESULTS: EFA indicated six primary themes (root mean square error of approximation (RMSEA)=0.040), including: (a) resources, (b) health status, (c) disability considerations, (d) lack of importance, (e) disincentives and (f) motivation. CFA indicated an acceptable fit (RMSEA=0.078). Univariate analyses indicated each item and factor was significantly different as a function of labor force participation. After controlling for biographical and injury factors, multinomial logistic regression indicated three factors significantly differentiated those never employed, those currently unemployed but had worked since injury and those currently employed. Those employed reported higher scores for resources and motivation and lower scores for lack of importance. CONCLUSIONS: Barriers and facilitators were consistently related to labor force participation, with facilitators more highly related to labor force participation than barriers. Although loss of financial and medical benefits (disincentives) as well as health status have been reported as barriers to employment, they were not as highly correlated with labor force participation as were other factors.

Prediction of somatic and non-somatic depressive symptoms between inpatient rehabilitation and follow-up.

STUDY DESIGN: Longitudinal. OBJECTIVE: We identified changes in the association of somatic and non-somatic symptoms (as measured by the Patient Health Questionnaire-9, PHQ-9) between inpatient rehabilitation after spinal cord injury (SCI) and 1 year after discharge. SETTING: A specialty hospital in the Southeastern USA. METHODS: A total of 584 adults with traumatic SCI were administered the PHQ-9 during inpatient rehabilitation. Of them, 227 completed the PHQ-9 by survey at 1-year follow-up. We performed time-lagged regression between times of measurement for somatic and non-somatic factors of the PHQ-9. RESULTS: The non-somatic factor at baseline was significantly predictive of the non-somatic (r=0.67, P=0.002) and somatic factors at follow-up (r=0.53, P=0.019). The somatic factor did not significantly predict either the somatic (r=0.10, n.s.) or non-somatic factors at follow-up (r=-0.01, NS). Factor analysis also indicated changing factor structure between inpatient rehabilitation and follow-up. CONCLUSIONS: Our results question the interpretation of somatic items during inpatient rehabilitation, as they are not predictive of either somatic or non-somatic symptoms at follow-up.

Adapting the Neuman systems model for family nursing.

Family nursing is in the early stages of development, and there is often difficulty in translating nursing conceptual frameworks into terms that are less abstract and more readily usable in the family practice arena. Yet the conversion of abstract ideas to concrete descriptions is necessary if nursing theory-based practice is to expand. This article describes the client system known as family within the Neuman systems model. Based on clinical data and the experience of nurses using the Neuman model in practice, a description of the family as client is developed. The five variables of Neuman's model are identified and the terms used in describing the family system are clarified. A rationale for the application is also presented.

The effects of gestational age and pregnancy planning status on obstetrical nurses' perceptions of giving emotional care to women experiencing miscarriage.

Obstetrical nurses (N = 292) were surveyed regarding the influence of gestational age and pregnancy planning on nurses' emotional care for women who had experienced miscarriage. Three measures of emotional care were used as the dependent variables: emotional seriousness, priority of care and emotional support. Both gestational age and whether the pregnancy was planned or unplanned had a significant effect on the nurses' perceptions of emotional seriousness and priority of care. Planning status was significant in the nurses' perception of emotional support.