Participatory Research Approaches with Youth: Ethics, Engagement, and Meaningful Action.

In this manuscript, we explore the promise and challenges of youth participatory action research (YPAR), paying particular attention to ethical issues and power dynamics that emerge in the context of research partnerships between youth and adults. We begin by reviewing the key tenets of YPAR and then go on to discuss how these tenets are often at odds with dominant approaches to research. We describe the tension between the values of YPAR and the systems and structures embedded in the academy. Further, we elucidate how adultism and the capitalist nature of the academy intersect with white supremacy culture, posing significant barriers to meaningful youth participation in community research partnerships. We then describe ways in which participatory scholars can disrupt these systems as well as larger paradigm shifts in the culture of academia that will be required to elevate youth voices and to amplify their efforts for equity.

Death and taxes: Examining the racial inequality in premature death across neighborhoods.

Legacies of residential segregation have led to deep inequities felt in communities of color across the nation and have been established as a fundamental cause of health disparities. Historical practices such as the redlining of majority Black neighborhoods in cities have led to long term consequences on these communities, including concentrated poverty and disadvantage. Research shows a strong connection between living in a poor neighborhood and poorer health outcomes, including early death, but questions remain about what characteristics of poor neighborhoods drive these disparities. We combined data from the American Community Survey with administrative data from Pittsburgh, Pennsylvania to examine the difference in premature death in Black and white neighborhoods (N = 87) using measures of socioeconomic disadvantage and less commonly studied neighborhood features including vacancy, tax delinquency, and property sales and conditions. Results suggest that features of abandonment, particularly the percent of tax delinquent properties in a neighborhood, may capture an important structural difference between majority Black and majority white neighborhoods with impacts beyond socioeconomic disadvantage on community health. We discuss implications of these findings for research and practice.

Genetics of Resistant Hypertension: the Missing Heritability and Opportunities.

PURPOSE OF THE REVIEW: Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use. Here, we propose the combined use of resistant hypertension as a trait for mapping genetic determinants in humans and the integration of new large-scale technologies to approach in model systems the multidimensional nature of the problem. RECENT FINDINGS: New large-scale efforts in the genetic and genomic arenas are paving the way for an increased and granular understanding of genetic determinants of hypertension. New technologies for whole genome sequence and large-scale forward genetic screens can help prioritize gene and gene-pathways for downstream characterization and large-scale population studies, and guided pharmacological design can be used to drive discoveries to the translational application through better risk stratification and new therapeutic approaches. Although significant challenges remain in the mapping and identification of genetic determinants of hypertension, new large-scale technological approaches have been proposed to surpass some of the shortcomings that have limited progress in the area for the last three decades. The incorporation of these technologies to hypertension research may significantly help in the understanding of inter-individual blood pressure variation and the deployment of new phenotyping and treatment approaches for the condition.

Neighborhood Social and Environmental Factors and Asthma Among Children Living in Low-Income Neighborhoods: The Importance of Informal Social Control.

Despite the knowledge that children in low-income neighborhoods are particularly vulnerable to asthma, few studies of child asthma focus on variation among low-income neighborhoods. We examined the relationship between child asthma and features associated with neighborhood poverty including safety, social cohesion, informal social control, collective efficacy, and disorder, across a sample of children from low-income neighborhoods (N = 3010; 2005-2007). Results show that the relationship between asthma and poverty is accounted for by family-level characteristics, but informal social control remains significantly and positively related to asthma after accounting for family-level characteristics. We discuss the importance of neighborhood environmental features for children's asthma.

Barrios, ghettos, and residential racial composition: Examining the racial makeup of neighborhood profiles and their relationship to self-rated health.

Racial/ethnic disparities in self-rated health persist and according to the social determinants of health framework, may be partially explained by residential context. The relationship between neighborhood factors and self-rated health has been examined in isolation but a more holistic approach is needed to understand how these factors may cluster together and how these neighborhood typologies relate to health. To address this gap, we conducted a latent profile analysis using data from the Chicago Community Adult Health Study (CCAHS; N = 2969 respondents in 342 neighborhood clusters) to identify neighborhood profiles, examined differences in neighborhood characteristics among the identified typologies and tested their relationship to self-rated health. Results indicated four distinct classes of neighborhoods that vary significantly on most neighborhood-level social determinants of health and can be defined by racial/ethnic composition and class. Residents in Hispanic, majority black disadvantaged, and majority black non-poor neighborhoods all had significantly poorer self-rated health when compared to majority white neighborhoods. The difference between black non-poor and white neighborhoods in self-rated health was not significant when controlling for individual race/ethnicity. The results indicate that neighborhood factors do cluster by race and class of the neighborhood and that this clustering is related to poorer self-rated health.

Reclaim Northside: An Environmental Justice Approach to Address Vacant Land in Pittsburgh.

Urban decline, disinvestment, and blight have not traditionally been addressed by the environmental conservation movement. In this article, we describe an environmental justice-focused intervention located in Pittsburgh, Pennsylvania, that aimed to increase community empowerment to address urban environmental injustices by training residents to reclaim vacant land. We use a case study approach to illustrate resident perceptions of the impact of vacant land and urban decay. The results suggest that these residents viewed vacancy as an important indicator of community well-being and social inequality. We use a social and environmental justice framework to describe results and implications for practitioners and researchers.

Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping.

We used N-ethyl-N-nitrosurea-induced germline mutagenesis combined with automated meiotic mapping to identify specific systolic blood pressure (SBP) and heart rate (HR) determinant loci. We analyzed 43,627 third-generation (G3) mice from 841 pedigrees to assess the effects of 45,378 variant alleles within 15,760 genes, in both heterozygous and homozygous states. We comprehensively tested 23% of all protein-encoding autosomal genes and found 87 SBP and 144 HR (with 7 affecting both) candidates exhibiting detectable hypomorphic characteristics. Unexpectedly, only 18 of the 87 SBP genes were previously known, while 26 of the 144 genes linked to HR were previously identified. Furthermore, we confirmed the influence of two genes on SBP regulation and three genes on HR control through reverse genetics. This underscores the importance of our research in uncovering genes associated with these critical cardiovascular risk factors and illustrate the effectiveness of germline mutagenesis for defining key determinants of polygenic phenotypes that must be studied in an intact organism.

Before and after AlphaFold2: An overview of protein structure prediction.

Three-dimensional protein structure is directly correlated with its function and its determination is critical to understanding biological processes and addressing human health and life science problems in general. Although new protein structures are experimentally obtained over time, there is still a large difference between the number of protein sequences placed in Uniprot and those with resolved tertiary structure. In this context, studies have emerged to predict protein structures by methods based on a template or free modeling. In the last years, different methods have been combined to overcome their individual limitations, until the emergence of AlphaFold2, which demonstrated that predicting protein structure with high accuracy at unprecedented scale is possible. Despite its current impact in the field, AlphaFold2 has limitations. Recently, new methods based on protein language models have promised to revolutionize the protein structural biology allowing the discovery of protein structure and function only from evolutionary patterns present on protein sequence. Even though these methods do not reach AlphaFold2 accuracy, they already covered some of its limitations, being able to predict with high accuracy more than 200 million proteins from metagenomic databases. In this mini-review, we provide an overview of the breakthroughs in protein structure prediction before and after AlphaFold2 emergence.

Using gene-network landscape to dissect genotype effects of TCF7L2 genetic variant on diabetes and cardiovascular risk.

The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker associated with Type 2 diabetes mellitus (T2DM) risk. Nonetheless, its functional role in disease pathology is poorly understood. The aim of the present study was to investigate, in vascular smooth muscle cells from 92 patients undergoing aortocoronary bypass surgery, the contribution of this SNP in T2DM using expression levels and expression correlation comparison approaches, which were visually represented as gene interaction networks. Initially, the expression levels of 41 genes (seven TCF7L2 splice forms and 40 other T2DM relevant genes) were compared between rs7903146 wild-type (CC) and T2DM-risk (CT + TT) genotype groups. Next, we compared the expression correlation patterns of these 41 genes between groups to observe if the relationships between genes were different. Five TCF7L2 splice forms and nine genes showed significant expression differences between groups. RXRα gene was pinpointed as showing the most different expression correlation pattern with other genes. Therefore, T2DM risk alleles appear to be influencing TCF7L2 splice form's expression in vascular smooth muscle cells, and RXRα gene is pointed out as a treatment target candidate for risk reduction in individuals with high risk of developing T2DM, especially individuals harboring TCF7L2 risk genotypes.

Social Work and Youth Participatory Action Research (YPAR): Past, Present, and Future.

The social work profession has made tremendous contributions to youth well-being, laying the foundation for social welfare systems and child protection laws. However, deficit-based constructions of youth are deeply engrained in the profession. Social work researchers have called for attention to critical approaches like youth participatory action research (YPAR). YPAR has an action-oriented epistemology and engages youth as coresearchers, providing an opportunity to shift social work research and practice paradigms. Yet, social work scholars lag behind cognate disciplines in adopting YPAR. This article examines challenges that have stymied YPAR in social work. The authors review the historical roots of the profession and its relationship to youth; examine present challenges, including social work's training and career progression; and make suggestions for the future, calling social work to affirm our values by reevaluating the way we do research on youth, the way we train future social workers, and the paradigms driving our practice.

Unaccompanied Immigrant Children in ORR Foster Care: Community Level Facilitators of Adjustment Identified by Service Providers.

PURPOSE: While many studies address immigrant integration, few focus on the adjustment process for unaccompanied immigrant children in foster care in the United States- and even fewer look at community level prevention and intervention strategies for positive youth adjustment. This study uses a human rights framework to examine community level facilitators- both prevention and interventions- that aid the adjustment for unaccompanied immigrant children in foster care as they navigate life in the US. METHOD: Seventy-nine service providers that work with unaccompanied immigrant children participated in 22 focus groups/interviews. Open coding was used to create a codebook, and then data were qualitatively analyzed using deductive and axial coding. RESULTS: The major prevention strategies for community adjustment include welcoming communities and inter-agency collaborations. The major intervention strategies for systems level adjustment include community relationships, access to healthcare, and the church as an institution. DISCUSSION: Implications include advocating for funding and programming to support mentors for every child, advocating for welcoming policies, and engaging unaccompanied immigrant children in research using participatory approaches.

Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors.

Endothelial dysfunction (ED) is a hallmark of atherosclerosis and is influenced by well-defined risk factors, including hypoxia, dyslipidemia, inflammation, and oscillatory flow. However, the individual and combined contributions to the molecular underpinnings of ED remain elusive. We used global gene expression in human coronary artery endothelial cells to identify gene pathways and cellular processes in response to chemical hypoxia, oxidized lipids, IL-1ß induced inflammation, oscillatory flow, and these combined stimuli. We found that clustering of the surrogate risk factors differed from the sum of the individual insults that gave rise to emergent phenotypes such as cell proliferation. We validated these observations in samples of human coronary artery atherosclerotic plaques analyzed using single-cell RNA sequencing. Our findings suggest a hierarchical interaction between surrogates of CV risk factors and the advent of emergent phenotypes in response to combined stimulation in endothelial cells that may influence ED.

Sex differences in the lung ACE/ACE2 balance in hypertensive rats.

The angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II) and angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7)) pathways are coexpressed in most tissues. The balance between these pathways determines, at least in part, whether tissue damage will occur in response to pathological stimuli. The present study tested the hypothesis that male sex and high blood pressure are associated with ACE/ACE2 imbalance in the lungs. Experiments were conducted in male and female Wistar rats and spontaneously hypertensive rats (SHRs). Lung ACE and ACE2 gene expression was also evaluated in normotensive and hypertensive humans using the Genotype-Tissue Expression (GTEx) project. Compared with Wistar rats and female SHRs, male SHRs displayed reduced lung ACE2 mRNA, ACE2 protein abundance and ACE2 activity, and increased Ang II concentration. Lung ACE mRNA levels were higher in male SHRs than in Wistar rats, whereas lung ACE protein abundance and activity were similar among the four groups of rats. Lung Ang-(1-7) concentration was higher in female than in male SHRs (89 ± 17 vs. 43 ± 2 pg/g, P<0.05). Lung ACE to ACE2 mRNA expression in hypertensive patients was significantly higher than that in normotensive subjects. Taken together, these results demonstrate that male hypertensive rats display imbalance between the ACE/Ang II and ACE2/Ang-(1-7) pathways in the lungs mainly attributable to ACE2 down-regulation. Further studies should be conducted to investigate whether this imbalance between ACE/ACE2 may promote and accelerate lung injury in respiratory infections, including coronavirus disease 2019 (COVID-19).

Carotid intima-media thickness and metabolic syndrome in a rural population: Results from the Baependi Heart Study.

BACKGROUND AND AIMS: Carotid intima-media thickness (cIMT) is a strong predictor of cardiovascular events and associated with metabolic syndrome (MetS). MetS is a cluster of cardiovascular risk factors, but the association structure between specific factors and disease development is not well-established in rural populations. We described the association structure between MetS factors and cIMT in a sample from rural Brazil. METHODS: We studied 1937 participants from the Baependi Heart Study who underwent carotid ultrasound exam. We used ATP-III-2001 for MetS definition and linear mixed-effects models, adjusting by the family structure, to assess independent associations between the cardiovascular risk factors which define MetS and cIMT. RESULTS: The sample's mean age was 46 ± 16y, 61% female, 73% white, mean body-mass-index 26±5 kg/m2, mean cIMT 0.53 ± 0.16 mm, with 35% of the sample classified with MetS. As expected, cIMT demonstrated a linear relationship with increasing age, and cIMT higher values were observed for MetS (0.58 ± 0.16 mm) compared to non-MetS (0.49 ± 0.14 mm). Considering models for cIMT with MetS and all of its factors, we found that blood pressure, glucose and obesity were independently associated with cIMT, but not HDL or triglycerides. CONCLUSIONS: cIMT showed a linear relationship with increasing age. Blood pressure, obesity, and glucose were independently associated with cIMT, but not HDL-cholesterol or triglycerides. In a rural population, hypertension, diabetes and obesity play a more important role than lipids in determining cIMT interindividual variability.

Residential Segregation and Racial/Ethnic Disparities in Ambient Air Pollution.

Race and ethnicity are consequential constructs when it comes to exposure to air pollution. Persistent environmental racial/ethnic inequalities call for attention to identifying the factors that maintain them. We examined associations between racial residential segregation and racial/ethnic inequalities in exposure to three types of air pollutants. Using data from the Panel Study of Income Dynamics (1990-2011), the U.S. Census (1990- 2010), and the Environmental Protection Agency, we tested the independent and joint contributions of race/ethnicity and metropolitan-level residential segregation on individual levels of exposure to air pollution nationwide. We found that racial and ethnic minorities were exposed to significantly higher levels of air pollution compared to Whites. The difference between minorities and Whites in exposure to all three types of air pollution was most pronounced in metropolitan areas with high levels of residential segregation. The environmental inequities observed in this study call for public health and policy initiatives to ameliorate the sources of racial/ethnic gaps in pollution exposure. Given the links between the physical environment and health, addressing such uneven environmental burdens may be a promising way to improve population health and decrease racial/ethnic inequalities therein.

The Power of Prevention and Youth Voice: A Strategy for Social Work to Ensure Youths' Healthy Development.

The opening plenary session at the 2017 Annual Conference of the Society for Social Work and Research, which focused on ensuring healthy youth development, highlighted the need to include young people as partners in research and evaluation. In doing so, the conference participants joined the voices of a growing group of social work scholars committed to youth participation and engagement, who have also highlighted the importance of youth voice in the development of prevention strategies and programming that are aligned with the lived experience of young people. Presenting four unique social work efforts designed to harness the power of youth voice, this article shines a spotlight on the role of social work research and practice in harnessing the power of youth participation in efforts of promote healthy youth development. This article concludes by illustrating the benefits of youth engagement for young people, communities, and researchers.

Early-Life Air Pollution Exposure, Neighborhood Poverty, and Childhood Asthma in the United States, 1990⁻2014.

Ambient air pollution is a well-known risk factor of various asthma-related outcomes, however, past research has often focused on acute exacerbations rather than asthma development. This study draws on a population-based, multigenerational panel dataset from the United States to assess the association of childhood asthma risk with census block-level, annual-average air pollution exposure measured during the prenatal and early postnatal periods, as well as effect modification by neighborhood poverty. Findings suggest that early-life exposures to nitrogen dioxide (NO2), a marker of traffic-related pollution, and fine particulate matter (PM2.5), a mixture of industrial and other pollutants, are positively associated with subsequent childhood asthma diagnosis (OR = 1.25, 95% CI = 1.10⁻1.41 and OR = 1.25, 95% CI = 1.06⁻1.46, respectively, per interquartile range (IQR) increase in each pollutant (NO2 IQR = 8.51 ppb and PM2.5 IQR = 4.43 µ/m³)). These effects are modified by early-life neighborhood poverty exposure, with no or weaker effects in moderate- and low- (versus high-) poverty areas. This work underscores the importance of a holistic, developmental approach to elucidating the interplay of social and environmental contexts that may create conditions for racial-ethnic and socioeconomic disparities in childhood asthma risk.

Using Local Data to Address Abandoned Property: Lessons Learned From a Community Health Partnership.

THE PROBLEM: A growing body of research highlights the role of the built environment in promoting or impeding health. This research suggests that environmental issues like abandoned properties exact a toll on physical and mental health. PURPOSE: We describe a community partnership aimed at improving community health through equitable land use policies and blight remediation. KEY POINTS: A collaboration between the University of Pittsburgh and Operation Better Block, Inc. (OBB), a community development corporation in Pittsburgh, was formed. We implemented an intervention to address property abandonment using data-driven techniques. In addition to successful advocacy for city-wide policies addressing abandonment, 80% of the properties that were part of our intervention were improved or addressed by the city. CONCLUSIONS: Balancing the needs of community and academic partners can be challenging, but our experiences suggest that community health partnerships to address built environmental issues may be an important conduit to health promotion.

Mapping the Racial Inequality in Place: Using Youth Perceptions to Identify Unequal Exposure to Neighborhood Environmental Hazards.

Black youth are more likely than white youth to grow up in poor, segregated neighborhoods. This racial inequality in the neighborhood environments of black youth increases their contact with hazardous neighborhood environmental features including violence and toxic exposures that contribute to racial inequality in youth health and well-being. While the concept of neighborhood effects has been studied at length by social scientists, this work has not been as frequently situated within an environmental justice (EJ) paradigm. The present study used youth perceptions gained from in-depth interviews with youth from one Pittsburgh, Pennsylvania neighborhood to identify neighborhood environmental health hazards. We then mapped these youth-identified features to examine how they are spatially and racially distributed across the city. Our results suggest that the intersection of race and poverty, neighborhood disorder, housing abandonment, and crime were salient issues for youth. The maps show support for the youths' assertions that the environments of black and white individuals across the city of Pittsburgh differ in noteworthy ways. This multi-lens, mixed-method analysis was designed to challenge some of the assumptions we make about addressing environmental inequality using youths' own opinions on the issue to drive our inquiry.