CRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer cell lines rather than ...healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes in such neurons and present results from three complementary genetic screens. First, a survival-based screen revealed neuron-specific essential genes and genes that improved neuronal survival upon knockdown. Second, a screen with a single-cell transcriptomic readout uncovered several examples of genes whose knockdown had strikingly cell-type-specific consequences. Third, a longitudinal imaging screen detected distinct consequences of gene knockdown on neuronal morphology. Our results highlight the power of unbiased genetic screens in iPSC-derived differentiated cell types and provide a platform for systematic interrogation of normal and disease states of neurons.
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•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival screens uncover genes essential for neurons, but not iPSCs or cancer cells•Single-cell RNA-seq screens reveal distinct neuronal roles for ubiquitous genes•Arrayed high-content screens uncover genes controlling neuronal morphology
Tian, Gachechiladze, and Ludwig et al. present a CRISPR interference-based platform for genetic screens in human iPSC-derived neurons. This platform enables systematic elucidation of gene function in human neurons and reveals neuron-specific roles of genes for survival, transcriptomics states, and morphology.
Objective:
Cognitive reserve has been proposed as important in the etiology of neuropsychiatric disorders. However, tests of the association between premorbid IQ and adult mental disorders other than ...schizophrenia have been limited and inconclusive. The authors tested the hypothesis that low childhood IQ is associated with increased risk and severity of adult mental disorders.
Method:
Participants were members of a representative 1972-1973 birth cohort of 1,037 males and females in Dunedin, New Zealand, who were followed up to age 32 with 96% retention. WISC-R IQ was assessed at ages 7, 9, and 11. Research diagnoses of DSM mental disorders were made at ages 18, 21, 26, and 32.
Results:
Lower childhood IQ was associated with increased risk of developing schizophrenia spectrum disorder, adult depression, and adult anxiety. Lower childhood IQ was also associated with greater comorbidity and with persistence of depression; the association with persistence of generalized anxiety disorder was nearly significant. Higher childhood IQ predicted increased risk of adult mania.
Conclusions:
Lower cognitive reserve, as reflected by childhood IQ, is an antecedent of several common psychiatric disorders and also predicts persistence and comorbidity. Thus, many patients who seek mental health treatment may have lower cognitive ability; this should be considered in prevention and treatment planning.
Health mindset is a group of beliefs or assumptions that individuals hold about the causes of health and well-being. Strengthening our understanding of factors that shape mindset and how mindset ...shapes expectations for who can and should be responsible for health can inform the success and sustainability of solutions to current health crises including the COVID-19 pandemic, ongoing disparities in health outcomes, and gun violence. We first examined associations between personal characteristics and experiences with health mindset. Next, we examined the association between mindset and the belief that government involvement can help address pressing health questions, using obesity as an example of a health outcome that is shaped both by personal choices and factors outside one’s control. Going forward, it will be important to consider health mindset in broader transformations of the health system and population approaches to improving health.
Abstract Purpose Since 2001, many military families have experienced multiple and extended deployments. Little is known about the effect of parental deployment on the well-being of children, and few, ...if any, studies to date have engaged school staff to understand whether and how parental deployments affect the behavioral, social, and emotional outcomes of youth in the school setting. Methods Focus groups and semi-structured interviews were conducted with teachers, counselors, and administrative staff at schools serving children from U.S. Army families (N = 148 staff). Participants were queried about the academic, behavioral, and emotional issues faced by children of deployed soldiers. Data were analyzed for themes in these areas, with attention to differences by service component (Active Component vs. Army Reserve and National Guard). Results Although some children seem to be coping well with deployment, school staff felt that children's anxiety related to parental absence, increased responsibilities at home, poor mental health of some nondeployed parents, and difficulty accessing mental health services affected the ability of other students to function well in school. Conclusions School staff felt that parental deployment negatively affected social and emotional functioning for some children and youth, although they felt others were coping well. Future research should examine factors related to youth outcomes during parental deployment (e.g., mental health of the non-deployed parent) and assess the effects of deployment on other measures of behavior such as school engagement and academic performance.
This report describes the study design and summary data from the first year of data collection for the Urban Child Institute Conditions Affecting Neurocognitive Development and Learning in Early ...Childhood Study: participant demographics, prenatal and birth measures; child and family health and nutrition; mothers’ mental and behavioral health; and cognitive performance, psychosocial measures, and biological samples for mothers and children.
The public health sector has long recognized the role of the social determinants of health in health disparities and the importance of achieving health equity. We now appear to be at an inflection ...point, as we hear increasing demands to dismantle structures that have perpetuated inequalities. Assessing prevailing mindsets about what causes health inequalities and the value of health equity is critical to addressing larger issues of inequity, including racial inequity and other dimensions. Using data from a nationally representative sample of adults in the United States, we examined the factors that Americans think drive health outcomes and their beliefs about the importance of health equity.
Using data from the 2018 National Survey of Health Attitudes, we conducted factor analyses of 21 survey items and identified three factors from items relating to health drivers-traditional health influencers (THI), social determinants of health (SDoH), and sense of community health (SoC). Health equity beliefs were measured with three questions about opportunities to be healthy. Latent class analysis identified four groups with similar patterns of response. Factor mixture modeling combined factor structure and latent class analysis into one model. We conducted three logistic regressions using latent classes and demographics as predictors and the three equity beliefs as dependent variables.
Nearly 90% of respondents comprised one class that was characterized by high endorsement (i.e., rating the driver as having strong effect on health) of THI, but lower endorsement of SDoH and SoC. Logistic regressions showed that respondents endorsing (i.e., rated it as a top priority) all three health equity beliefs tended to be female, older, Black or Hispanic, more educated, and have lower incomes. The class of respondents that endorsed SDoH the most was more likely to endorse all three equity beliefs.
Results suggested that people historically impacted by inequity, e.g., people of color and people with low incomes, had the most comprehensive understanding of the drivers of health and the value of equity. However, dominant beliefs about SDoH and health equity are still generally not aligned with scientific consensus and the prevailing narrative in the public health community.
Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing ...evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.
Developing Predictive Models of Health Literacy Martin, Laurie T.; Ruder, Teague; Escarce, José J. ...
Journal of general internal medicine : JGIM,
11/2009, Volume:
24, Issue:
11
Journal Article
Peer reviewed
Open access
INTRODUCTION
Low health literacy (LHL) remains a formidable barrier to improving health care quality and outcomes. Given the lack of precision of single demographic characteristics to predict health ...literacy, and the administrative burden and inability of existing health literacy measures to estimate health literacy at a population level, LHL is largely unaddressed in public health and clinical practice. To help overcome these limitations, we developed two models to estimate health literacy.
METHODS
We analyzed data from the 2003 National Assessment of Adult Literacy (NAAL), using linear regression to predict mean health literacy scores and probit regression to predict the probability of an individual having ‘above basic’ proficiency. Predictors included gender, age, race/ethnicity, educational attainment, poverty status, marital status, language spoken in the home, metropolitan statistical area (MSA) and length of time in U.S.
RESULTS
All variables except MSA were statistically significant, with lower educational attainment being the strongest predictor. Our linear regression model and the probit model accounted for about 30% and 21% of the variance in health literacy scores, respectively, nearly twice as much as the variance accounted for by either education or poverty alone.
CONCLUSIONS
Multivariable models permit a more accurate estimation of health literacy than single predictors. Further, such models can be applied to readily available administrative or census data to produce estimates of average health literacy and identify communities that would benefit most from appropriate, targeted interventions in the clinical setting to address poor quality care and outcomes related to LHL.
The American Heart Association's national goals for cardiovascular health promotion emphasize that cardiovascular risk originates early in life, but little is known about childhood factors that may ...increase the likelihood of having a favorable cardiovascular risk (FCR) in adulthood. We examined the prospective association between positive childhood factors and the likelihood of midlife FCR. We also considered pathways through which childhood factors may influence FCR.
We studied 415 adults (mean age=42.2 years) of the Collaborative Perinatal Project, a national cohort initiated in 1959 to 1966. We examined 3 positive childhood factors assessed at age 7 years: attention regulation (ability to stay focused), cognitive ability, and positive home environment. Of these adults, 10.6% had FCR in midlife. Adjusting for demographics and childhood cardiovascular health, a 1-unit increase in childhood attention regulation, cognitive ability, and positive home environment was associated with 2.4 (95% confidence interval, 1.1-4.7), 1.8 (95% confidence interval, 1.1-2.9), and 1.3 (95% confidence interval, 1.1-1.6) higher respective odds of having midlife FCR. The association with childhood attention regulation was maintained when accounting for adulthood factors; education and diet in part explained the associations with childhood cognitive ability and home environment. The effect of each attribute was additive as those with high levels of each childhood factor had 4.3 higher odds (95% confidence interval, 1.01-18.2) of midlife FCR in comparison with those low in all factors.
Positive childhood psychosocial factors may promote healthy adult cardiovascular functioning. Primordial prevention efforts aimed at preventing the development of cardiovascular risk should consider building on childhood psychosocial resources.
Off to a Good Start Martin, Laurie T; Sontag-Padilla, Lisa; Cannon, Jill S ...
RAND Corporation,
01/2015
eBook, Book
Open access
Drawing on national, state, and local data, the Urban Child Institute partnered with RAND to explore the social and emotional well-being of children in Memphis and Shelby County, Tenn. The book ...highlights the importance of factors in the home, child care setting, and community that contribute to social and emotional development.
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