Leveraging the transcriptome to further our understanding of GWAS findings: eQTLs associated with genes related to LDL and LDL subclasses, in a cohort of African Americans.

Background: GWAS discoveries often pose a significant challenge in terms of understanding their underlying mechanisms. Further research, such as an integration with expression quantitative trait locus (eQTL) analyses, are required to decipher the mechanisms connecting GWAS variants to phenotypes. An eQTL analysis was conducted on genes associated with low-density lipoprotein (LDL) cholesterol and its subclasses, with the aim of pinpointing genetic variants previously implicated in GWAS studies focused on lipid-related traits. Notably, the study cohort consisted of African Americans, a population characterized by a heightened prevalence of hypercholesterolemia. Methods: A comprehensive differential expression (DE) analysis was undertaken, with a dataset of 17,948 protein-coding mRNA transcripts extracted from the whole-blood transcriptomes of 416 samples to identify mRNA transcripts associated with LDL, with further granularity delineated between small LDL and large LDL subclasses. Subsequently, eQTL analysis was conducted with a subset of 242 samples for which whole-genome sequencing data were available to identify single-nucleotide polymorphisms (SNPs) associated with the LDL-related mRNA transcripts. Lastly, plausible functional connections were established between the identified eQTLs and genetic variants reported in the GWAS catalogue. Results: DE analysis revealed 1,048, 284, and 94 mRNA transcripts that exhibited differential expression in response to LDL, small LDL, and large LDL, respectively. The eQTL analysis identified a total of 9,950 significant SNP-mRNA associations involving 6,955 SNPs including a subset 101 SNPs previously documented in GWAS of LDL and LDL-related traits. Conclusion: Through comprehensive differential expression analysis, we identified numerous mRNA transcripts responsive to LDL, small LDL, and large LDL. Subsequent eQTL analysis revealed a rich landscape of eQTL-mRNA associations, including a subset of eQTL reported in GWAS studies of LDL and related traits. The study serves as a testament to the important role of integrative genomics in unraveling the enigmatic GWAS relationships between genetic variants and the complex fabric of human traits and diseases.

Cultivating Relationships as a Community-Based Recruitment Strategy in Transdisciplinary Aging Research: Lessons From an Academic-Community Partnership.

Participation of Black American older adults in community-engaged research remains challenging in health sciences. The objectives of this study were to describe the specific efforts, successes, and challenges in recruiting Black American older adults in research led by the Health and Wellness in Aging Across the Lifespan core, part of the Virginia Commonwealth University Institute for Inclusion, Inquiry, and Innovation (iCubed). We conducted a cross-case analysis of 6 community-engaged research projects using the community-engaged research continuum model. Successful recruitment strategies comprised a multifaceted approach to community-based collaboration, including a wellness program with a long standing relationship with the community, engaging key stakeholders and a community advisory board, and building a community-based coalition of stakeholders. Posting flyers and modest monetary compensation remain standard recruitment strategies. The cross-case analysis offered critical lessons on the community's nature and level of engagement in research. Relationship building based on trust and respect is essential to solving complex aging issues in the community.

Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.

Introduction: The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Methods: Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Results: Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Discussion: In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Challenges and opportunities faced by nurse scientists in integrating data and technology in research to promote health equity.

Advances in technologies including omics, apps, imaging, sensors, and big data are increasingly being integrated into research by nurse scientists, but the impact on improving health equity is still unclear. In this article, nursing research faculty from one institution discuss challenges and opportunities experienced when integrating various technologies into their research aimed at promoting health equity. Using exemplars from faculty experiences, a three-pronged approach to keeping patients and communities and the goal of health equity central in research while incorporating advancing technologies is described. This approach includes establishing long-term engagement with populations underrepresented in research, adopting strategies to increase diversity in study participant recruitment, and training and collaboration among a diverse workforce of educators, clinicians, and researchers. Training nurse scientists in integrating data and technology for advancing the science on health equity will shift the culture of how we understand, collaborate, and grow with the communities in which we train and practice as nurse scientists.

Administration of Bifidobacterium animalis subsp. lactis Strain BB-12 ® in Healthy Children: Characterization, Functional Composition, and Metabolism of the Gut Microbiome.

The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two ( Streptococcus thermophilus and Lactobacillus delbrueckii ; S2) vs . three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10 . In the S2+BB12 group, the abundance of several fecal metabolites was reduced at Day 10 , including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Creating structural community cohesion: Addressing racial equity in older adult homelessness.

Older adults and racial minorities are overrepresented in homeless populations. Shelter and housing options for homeless older adults who have complex health and social needs are necessary, but not readily available. Older homeless adults that require, but do not receive, health-sensitive, age-sensitive, and racial equity housing, remain vulnerable to poor outcomes and premature mortality. Accordingly, this study examines the development of a coalition to better address older adult homelessness within a racial equity framework. A community coalition was established to better address older adult homelessness within the lens of age-sensitivity and racial equity, due to a disconnect between healthcare and senior housing placement programs, creating unaddressed multifaceted health issues/complications. The community coalition development is described, including the coalition process, activities, and outcomes. Local rehoused older adults are also interviewed and described to better understand their central life circumstances.

Understanding the preference for receiving mental health and substance use support in African Americans 50 and older.

OBJECTIVE: This study aims to determine whether current tobacco and/or alcohol use is associated with setting preferences for seeking support for substance use (SU) and mental health (MH) services to African Americans ages 50 and older. METHODS: Data from 368 African American individuals (aged 50+) who participated in a community-based needs assessment survey were used. Preferences included community-based (e.g., health centers) and traditional settings (e.g., doctor's office). SU was measured as a categorical variable detailing past-month use of conventional cigarettes and alcohol graded by risk levels. Logistic regression models tested the associations between SU and setting preference before and after adjusting for the influence of self-reported MH diagnoses. RESULTS: Prior to adjustment for the influence of MH outcomes, high-risk use of tobacco and alcohol in the past month was associated with a lower odds of preferring MH/SU support in traditional settings (OR = 0.23, 95% CI = 0.06-0.85) compared to participants engaged in no-/low- risk substance use. This association was no longer significant after accounting for the influence of mental health symptoms and covariates. DISCUSSION: These results provide preliminary evidence that mental health outcomes mediate the association between substance use and setting preference for seeking MH/SU support in traditional settings. TRANSLATIONAL SIGNIFICANCE: This exploratory study encourages additional investigation of the association between substance use, setting preferences, and the likelihood of seeking treatment in community health centers using larger sample sizes. Additional opportunities to offer mental health/substance use support to African American older adults within clinical settings should be explored.

Addressing challenges faced by underrepresented biomedical investigators and efforts to address them: An NHLBI-PRIDE perspective.

Junior investigators from groups underrepresented in the biomedical workforce confront challenges as they navigate the ranks of academic research careers. Biochemical research needs the participation of these researchers to adequately tackle critical research priorities such as cardiovascular health disparities and health inequities. We explore the inadequate representation of underrepresented minority investigators and the historical role of systemic racism in impacting their poor career progression. We highlight challenges these investigators face, and opportunities to address these barriers are identified. Ensuring adequate recruitment and promotion of underrepresented biomedical researchers fosters inclusive excellence and augments efforts to address health inequities. The Programs to Increase Diversity among Individuals Engaged in Health-Related Research (PRIDE), funded by the National Heart, Lung, and Blood Institute (NHLBI), is a pilot program by the National Institutes of Health (NIH) that aims to address these challenges yet, only a limited number of URM can be accepted to PRIDE programs. Hence the need for additional funding for more PRIDE or PRIDE-like programs. Here we aim to examine the challenges underrepresented minority biomedical investigators face and describe ongoing initiatives to increase URM in biomedical research using the NHLBI-PRIDE program as a focus point.

COVID in Context: The Lived Experience of Richmond's Low-Income Older Adults.

Taking a phenomenological approach, this qualitative study describes the lived experiences of low-income older adults during the COVID-19 pandemic. A socio-ecological model was used to organize the five identified themes describing the lived experience: socio-economic context, Black Lives Matter and the politics of race, COVID and polarized views of COVID, interpersonal context (social connections), and individual context (feelings, beliefs, and behaviors). Study findings illustrate the intersectionality of contextual influences on the experience of low-income older adults. Study participants demonstrated remarkable resilience and coping strategies developed in response to the challenges they experienced throughout their lifetime which benefited them when faced with the pandemic, social unrest, and political events that took place in 2020. This study highlights the importance of understanding the larger context of COVID-19 which has significant implications for policy makers and public health leaders.

Socioeconomic Effects on Psychosocial Factors Among Low-Income Older Adults.

OBJECTIVES: Older adults have been disproportionately affected by COVID-19. The primary goal of this study is to determine the socioeconomic effects on psychosocial factors among low-income independent-living older adults, in an urban setting, during the COVID-pandemic. METHODS: Participants were recruited through Virginia Commonwealth University's Richmond Health and Wellness Program. Telephone surveys (n=100) were conducted using the Epidemic - Pandemic Impacts Inventory Geriatric with the Racial/Ethnic Discrimination addendum. Responses were analyzed for income and education effects across seven domains: home life, social activities/isolation, economic, emotional health-wellbeing, physical health, COVID-infection history, and positive change behaviors/experiences. RESULTS: The sample population was between 51 and 87 years of age, 88% were Black, 57% reported incomes of $10,000/year or less, and 60% reported a high-school education or less. There were income effects for social activities/isolation (f = 3.69, p<.05) and positive change (f = 8.40, p<.01), and education effects for COVID History (f = 4.20, p <.04). DISCUSSION: Overall results highlight the social patterns for a diverse sample of low-income urban older adults; education and income are identified as risk factors for social losses, COVID-infection experiences, racial/ethnic discrimination during the COVID-pandemic, and positive change behaviors.

Bringing Transdisciplinary Aging Research From Theory to Practice.

There is a growing emphasis to use a transdisciplinary team approach to accelerate innovations in science to solve complex conditions associated with aging. However, the optimal organizational structure and process for how to accomplish transdisciplinary team science is unclear. In this forum, we illustrate our team's experience using transdisciplinary approaches to solve challenging and persistent problems for older adults living in urban communities. We describe our challenges and successes using the National Institutes of Health four-phase model of transdisciplinary team-based research. Using a de-identified survey, the team conducted an internal evaluation to identify features that created challenges including structural incongruities, interprofessional blind spots, group function, and group dynamics. This work resulted in the creation of the team's Transdisciplinary Conceptual Model. This model became essential to understanding the complex interplay between societal factors, community partners, and academic partners. Conducting internal evaluations of transdisciplinary team processes is integral for teams to move beyond the multi- and interdisciplinary niche and to reach true transdisciplinary success. More research is needed to develop measures that assess team transdisciplinary integration. Once the process of transdisciplinary integration can be reliably assessed, the next step would be to determine the impact of transdisciplinary team science initiatives on aging communities.

Training Underrepresented Early-Career Faculty in Cardiovascular Health Research during COVID-19: Structural Inequities and Health Disparity.

The COVID-19 pandemic has highlighted race-based health disparities and structural racism in the United States. Enhancing the training of early-career academic and health scientists from underrepresented minority groups (URM) is critical to reduce disparities affecting underserved population groups. A dedicated training program that has been proven to support URM can facilitate career development for junior faculty during the pandemic. This critical support ensures the retention of talented, racially diverse junior faculty who are poised to mitigate structural racism, rather than perpetuate it. We describe how the Cardiovascular Disease Programs to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE-CVD) summer institute successfully transitioned from a face-to-face format to a virtual format during the COVID-19 pandemic. As a result, early-career faculty continued to receive the PRIDE-CVD training on research methodology, grantsmanship, career development, and CVD health disparities, especially as related to the pandemic. In addition, the virtual format facilitated networking, promoted mental wellness, and allowed continual mentorship. Collectively, the program provided timely and relevant career development in the COVID-19 era and helped participants navigate the psychosocial challenges of being a URM in cardiovascular health research.

The Translational Approaches to Personalized Health Collaborative: Pharmacogenomics for African American Older Adults.

Older adults (i.e., 60 years and older), are the leading consumers of medications, and consequently are suffering the most from medication-related adverse events. Not only are older adults the largest consumers of medications, they are more likely to experience an adverse drug event contributing to increased hospitalization, utilization of emergency medical services, and mortality. Translational Approaches to Personalized Health (TAPH) is a transdisciplinary team of researchers conducting community-engaged participatory research focused on the discovery and translation of pharmacogenomic (PGx) data to improve health outcomes. Underserved and ethnically diverse older adults living in urban settings are significantly under-represented in PGx studies. To address the issue of under-representation, our study enrolls older African American adults into a community-based PGx study. Therefore, we will characterize the frequency of actionable PGx genotypes and identify novel PGx response genes in our cohort of older community dwelling African Americans. The translational component of our work is to use the PGx findings to improve therapeutic outcomes for medication management in older adults. Such findings will serve as a foundation for translational PGx studies aimed at improving medication efficacy and safety for older adults. In this article, we describe the process for launching the TAPH collaborative group, which includes the transdisciplinary team, community-engaged participatory research model, study measures, and the evaluation of PGx genes.

The Healthy Meal Program: A food insecurity screening and referral program for urban dwelling older adults.

OBJECTIVE: To describe the Healthy Meal Program (HMP), a community-academic partnership that aims to address the food insecurity and social isolation in older adults living in an urban setting. PROGRAM IMPLEMENTATION: Low-income older adults were screened for food insecurity and social isolation. A partnership with the food bank and a farm-based organization helped provide a weekly congregate or home-delivered meal, pilot a cooking class, and offer a mobile market selling fresh vegetables at discounted prices. PROGRAM EVALUATION: Overall, 339 individuals agreed to participate in the screening process. Sixty-eight percent (n = 230) screened positive for food insecurity and 41% (n = 139) screened positive for social isolation. Among individuals who were food insecure, 159 were referred to a food commodity program, 31 to meals on wheels, 23 to Supplemental Nutrition Assistance Program benefits, and 28 to emergency food pantries. The mobile market served 75 participants weekly and 15 individuals took part in cooking classes. CONCLUSIONS: Screening for food insecurity and social isolation in the HMP helped to assess the prevalence of these social determinants of health in low-income older adults. Weekly congregate meals, home visits, and group cooking classes were initiatives taken to decrease the impact of food insecurity and social isolation in this vulnerable population.

A case study in rapid adaptation of interprofessional education and remote visits during COVID-19.

The Richmond Health and Wellness Program (RHWP) is an innovative interprofessional care coordination program that seeks to support the health and wellness of independent-living older adults and educate future practitioners. Since 2012, RHWP has provided community-based interprofessional training to students at Virginia Commonwealth University. The sudden suspension of clinical and community-based training due to the COVID-19 pandemic created the need to transform the traditional ways students received clinical education and support the vulnerable communities served by RHWP. This paper describes RHWP's rapid transition to a hybrid telephone-based program with a virtual learning component for students which allowed RHWP to continue serving its participants and provide interprofessional training experiences. Since the transition, RHWP has served 111 participants through over 400 telephonic visits, and 12 nurse practitioner and pharmacy students completed clinical hours to fulfill graduation requirements. To meet the needs of learners, interprofessional education models can be adapted to changing circumstances posed by COVID-19.

Metabolic Profiling of Blood and Urine for Exploring the Functional Role of the Microbiota in Human Health.

The quantification of metabolites in blood and urine allows nurses to explore new hypotheses about the microbiome. This review summarizes findings from recent studies with a focus on how the state of the science can influence future nursing research initiatives. Metabolomics can advance nursing research by identifying physiologic/pathophysiologic processes underlying patients' symptoms and can be useful for testing the effects of nursing interventions. To date, metabolomics has been used to study cardiovascular, respiratory, endocrine, autoimmune, and infectious conditions, with research focused on understanding the microbial metabolism of substrates resulting in circulating/excreted biomarkers such as trimethylamine N-oxide. This review provides specific recommendations for the collection of specimens and goals for future studies.

Feeding modes, duration, and diarrhea in infancy: Continued evidence of the protective effects of breastfeeding.

OBJECTIVES: To evaluate the effect of early breastfeeding cessation on incidence of diarrhea in a cohort of U.S. infants. DESIGN, SAMPLE, AND MEASUREMENTS: A secondary data analysis was conducted using data from 2,340 mother-infant dyads participating in the Infant Feeding Practices Study II. We examined associations between duration of feeding type (e.g., exclusive breastfeeding [EBF], any breastfeeding [BF], formula feeding) and incidence of diarrhea before one year. RESULTS: The sample included mother-infant dyads that were 86.2% White, 3% Black, and 5% Hispanic. Interruption of EBF before 3 months was significantly associated with higher odds of having diarrhea at 6 months (OR = 1.80, p value ≤ 0.01) and between 6 and 12 months (OR = 1.45, p ≤ .01). Breastfeeding interruption before 6 months was associated with higher odds of having diarrhea at 6 months (OR = 3.19, p ≤ .01). Formula feeding for ≥3 months was associated with higher odds of diarrhea between 6 and 12 months. CONCLUSIONS: Exclusive breastfeeding for 3 months accompanied by any breastfeeding for 6 months provided the most protective effect against diarrhea. Public health interventions should address disparities in breastfeeding practices and provide support across clinical, workplace and community settings. Research should include more diverse population groups.

Considerations When Designing a Microbiome Study: Implications for Nursing Science.

Nurse scientists play an important role in studying complex relationships among human genetics, environmental factors, and the microbiome, all of which can contribute to human health and disease. Therefore, it is essential that they have the tools necessary to execute a successful microbiome research study. The purpose of this article is to highlight important methodological factors for nurse scientists to consider when designing a microbiome study. In addition to considering factors that influence host-associated microbiomes (i.e., microorganisms associated with organisms such as humans, mice, and rats), this manuscript highlights study designs and methods for microbiome analysis. Exemplars are presented from nurse scientists who have incorporated microbiome methods into their program of research. This review is intended to be a resource to guide nursing-focused microbiome research and highlights how study of the microbiome can be incorporated to answer research questions.

Colon Epithelial MicroRNA Network in Fatty Liver.

Background & Aims: Intestinal barrier alterations are associated with fatty liver (FL) and metabolic syndrome (MetS), but microRNA (miR) signaling pathways in MetS-FL pathogenesis remain unclear. This study investigates an epithelial-focused miR network in colorectal cell models based on the previously reported MetS-FL miR trio of hsa-miR-142-3p, hsa-miR-18b, and hsa-miR-890. Methods: Each miR mimic construct of MetS-FL miR trio was transfected into human colorectal cells, CRL-1790 or Caco-2. Global miRNome changes posttransfection were profiled (nCounter® Human v3 miRNA, NanoString Technologies). Changes in barrier (transepithelial electrical resistance, TEER) and epithelial cell junction structure (Occludin and Zona Occludens-1/ZO-1 immunofluorescence staining-confocal microscopy) were examined pre- and posttransfection in Caco-2 cell monolayers. A signaling network was constructed from the MetS-FL miR trio, MetS-FL miR-induced colorectal miRNome changes, ZO-1, and Occludin. Results: Transfection of CRL-1790 cells with each MetS-FL miR mimic led to global changes in the cellular miRNome profile, with 288 miRs being altered in expression by more than twofold. Eleven miRs with known cytoskeletal and metabolic roles were commonly altered in expression by all three miR mimics. Transfection of Caco-2 cell monolayers with each MetS-FL miR mimic induced barrier-associated TEER variations and led to structural modifications of ZO-1 and Occludin within epithelial cell junctions. Pathway analysis incorporating the MetS-FL miR trio, eleven common target miRs, ZO-1, and Occludin revealed a signaling network centered on TNF and AKT2, which highlights injury, inflammation, and hyperplasia. Conclusions: Colon-specific changes in epithelial barriers, cell junction structure, and a miRNome signaling network are described from functional studies of a MetS-FL miR trio signature.

Simple lateral flow assays for microbial detection in stool.

Diarrheal diseases claim the lives of 1300 children daily, mostly in the developing world. We have developed a simple lateral flow assay capable of detecting E. coli and EPEC DNA and RNA rapidly (<15 minutes) at the point-of-need, directly from stool without nucleic acid extraction or molecular amplification. The limit of detection of the method is 1 nM using synthetic DNA target substrates spiked into stool. However, due to the endogenous amplification of the 23S rRNA targets, we were able to detect the endogenous EPEC in pea-sized (5 mg) stool without labor-intensive and time-consuming nucleic acid purification or target amplification using enzymes. The significance of this method is that it is rapid (<15 minutes) and simple (without nucleic acid purification or molecular amplification) and does not require instrumentation, or access to a laboratory, cold chain or electric power. Thus, it is well-suited for point-of-need use in remote and/or resource-limited settings in the developing world where the mortality due to diarrheal diseases is especially high. The rapid testing of stool pathogens in real time at the point-of-need will decrease the loss of patients to follow-up, and enable patients to be treated earlier with the appropriate therapeutics in both the developed and developing world settings.