Human microbiome variation associated with race and ethnicity emerges as early as 3 months of age.

Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes racial and ethnic categories with 87% accuracy. Importantly, predictive genera are also among the top 30 most important taxa when childhood microbiomes are used to predict adult self-identified race and ethnicity. Our results highlight a critical developmental window at or shortly after 3 months of age when social and environmental factors drive race and ethnicity-associated microbiome variation and may contribute to adult health and health disparities.

Infection of dogs with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19)1,2. In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog3. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Here, using PCR with reverse transcription, serology, sequencing the viral genome and virus isolation, we show that 2 out of 15 dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected with SARS-CoV-2. SARS-CoV-2 RNA was detected in five nasal swabs collected over a 13-day period from a 17-year-old neutered male Pomeranian. A 2.5-year-old male German shepherd was positive for SARS-CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Antibody responses were detected in both dogs using plaque-reduction-neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The dogs remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans.

Fluidic shear stress alters clathrin dynamics and vesicle formation in endothelial cells.

Endothelial cells (ECs) experience a variety of highly dynamic mechanical stresses. Among others, cyclic stretch and increased plasma membrane tension inhibit clathrin-mediated endocytosis (CME) in non-ECs. It remains elusive how ECs maintain CME in these biophysically unfavorable conditions. Previously, we have used simultaneous two-wavelength axial ratiometry (STAR) microscopy to show that endocytic dynamics are similar between statically cultured human umbilical vein endothelial cells (HUVECs) and fibroblast-like Cos-7 cells. Here, we asked whether biophysical stresses generated by blood flow influence CME. We used our data processing platform-DrSTAR-to examine if clathrin dynamics are altered in HUVECs after experiencing fluidic shear stress (FSS). We found that HUVECs cultivated under a physiological level of FSS had increased clathrin dynamics compared with static controls. FSS increased both clathrin-coated vesicle formation and nonproductive flat clathrin lattices by 2.3-fold and 1.9-fold, respectively. The curvature-positive events had significantly delayed curvature initiation relative to clathrin recruitment in flow-stimulated cells, highlighting a shift toward flat-to-curved clathrin transitions in vesicle formation. Overall, our findings indicate that clathrin dynamics and clathrin-coated vesicle formation can be modulated by the local physiological environment and represent an important regulatory mechanism.

Resting-state MRI reveals spontaneous physiological fluctuations in the kidney and tracks diabetic nephropathy in rats.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion. Numerous other mechanisms can lead to fluctuations in perfusion and flow. The ability to monitor these spontaneous physiological fluctuations in vivo could facilitate the early detection of kidney disease. The goal of this work was to investigate the use of resting-state magnetic resonance imaging (rsMRI) to detect spontaneous physiological fluctuations in the kidney. We performed rsMRI of rat kidneys in vivo over 10 min, applying motion correction to resolve time series in each voxel. We observed spatially variable, spontaneous fluctuations in rsMRI signal between 0 and 0.3 Hz, in frequency bands associated with autoregulatory mechanisms. We further applied rsMRI to investigate changes in these fluctuations in a rat model of diabetic nephropathy. Spectral analysis was performed on time series of rsMRI signals in the kidney cortex and medulla. The power from spectra in specific frequency bands from the cortex correlated with severity of glomerular pathology caused by diabetic nephropathy. Finally, we investigated the feasibility of using rsMRI of the human kidney in two participants, observing the presence of similar, spatially variable fluctuations. This approach may enable a range of preclinical and clinical investigations of kidney function and facilitate the development of new therapies to improve outcomes in patients with kidney disease.NEW & NOTEWORTHY This work demonstrates the development and use of resting-state MRI to detect low-frequency, spontaneous physiological fluctuations in the kidney consistent with previously observed fluctuations in perfusion and potentially due to autoregulatory function. These fluctuations are detectable in rat and human kidneys, and the power of these fluctuations is affected by diabetic nephropathy in rats.

The Detection of Environmental Influences on Academic Achievement Appears to Depend on the Analytic Approach.

One long-standing analytic approach in adoption studies is to examine correlations between features of adoptive homes and outcomes of adopted children (hereafter termed 'measured environment correlations') to illuminate environmental influences on those associations. Although results from such studies have almost uniformly suggested modest environmental influences on adopted children's academic achievement, other work has indicated that adopted children's achievement is routinely higher than that of their reared-apart family members, often substantially so. We sought to understand this discrepancy. We examined academic achievement and literacy-promotive features of the home in 424 yoked adoptive/biological families participating in the Early Growth and Development Study (EGDS; i.e., adopted children, adoptive mothers, birth mothers, and biological siblings of the adopted children remaining in the birth homes) using an exhaustive modeling approach. Results indicated that, as anticipated, adopted children scored up to a full standard deviation higher on standardized achievement tests relative to their birth mothers and reared-apart biological siblings. Moreover, these achievement differences were associated with differences in the literacy-promotive features of the adoptive and birth family homes, despite minimal measured environment correlations within adoptive families. A subsequent simulation study highlighted noise in measured environmental variables as an explanation for the decreased utility of measured environment correlations. We conclude that the field's heavy focus on measured environment correlations within adoptive families may have obscured detection of specific environmental effects on youth outcomes, and that future adoption studies should supplement their measured environment analyses with mean differences between reared-apart relatives.

Life satisfaction for adolescents with developmental and behavioral disabilities during the COVID-19 pandemic.

BACKGROUND: This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. METHODS: Data were collected from a sample of 1084 adolescents aged 11-21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities. RESULTS: Adolescents with a history of depression, anxiety, autism, and attention-deficit/hyperactivity disorder were particularly susceptible to decreased life satisfaction in response to unique combinations of stressors experienced during the COVID-19 pandemic. These stressors included decreased social connectedness, decreased family engagement, stress related to medical care access, pandemic-related traumatic stress, and single-caregiver households. CONCLUSION: Findings from this study highlight the importance of interventions aimed specifically at increasing adolescent social connectedness, family engagement, and access to medical support for adolescents with MEBD disabilities, particularly in the face of stressors, such as a global pandemic. IMPACT: Through a machine learning process, we identified contextualized risks associated with life satisfaction among adolescents with neurodevelopmental disabilities during the COVID-19 pandemic. The COVID-19 pandemic resulted in large-scale social disruptions for children and families. Such disruptions were associated with worse mental health outcomes in the general pediatric population, but few studies have examined specific subgroups who may be at heightened risk. We endeavored to close that gap in knowledge. This study highlights the importance of social connectedness, family engagement, and access to medical support as contributing factors to life satisfaction during the COVID-19 pandemic for adolescents with neurodevelopmental disabilities.

A Translational Case Study of a Multisite COVID-19 Public Health Intervention Across Sequenced Research Trials: Embedding Implementation in a Community Engagement Phased Framework.

Through a COVID-19 public health intervention implemented across sequenced research trials, we present a community engagement phased framework that embeds intervention implementation: (1) consultation and preparation, (2) collaboration and implementation, and (3) partnership and sustainment. Intervention effects included mitigation of psychological distress and a 0.28 increase in the Latinx population tested for SARS-CoV-2. We summarize community engagement activities and implementation strategies that took place across the trials to illustrate the value of the framework for public health practice and research. (Am J Public Health. 2024;114(S5):S396-S401. https://doi.org/10.2105/AJPH.2024.307669).

Community Partner Perceptions of Equitable Implementation Practices for a Promotores de Salud Intervention: A Qualitative Assessment.

We conducted focus groups with staff from 5 community-based organizations (21 participants; 86% female, 52% Hispanic/Latino/a/x and 24% Mexican/Mexican American) between August and October 2021. Results highlighted community partner perceptions of practices congruent (e.g., communication that built trust and dismantled power dynamics, a shared mission) and incongruent (e.g., intervention-community misalignment, research driven decision-making) with equitable implementation in the development, implementation, and evaluation of a promotores de salud intervention to increase COVID-19 testing and preventive behaviors among Latinx communities in Oregon. (Am J Public Health. 2024;114(S5):S377-S383. https://doi.org/10.2105/AJPH.2024.307686).

Changes in Stigma and Social Support among Participants in a Randomized Trial of a Novel Expanded Social Network-based HIV Testing Intervention in KwaZulu-Natal, South Africa.

HIV-related stigma is a well-documented barrier to HIV testing in South Africa, and may be particularly likely to create reluctance to test among South African men, who have reported feeling blamed for HIV by their partners and communities. The present study presents a novel expanded social network recruitment to HIV testing (E-SNRHT) intervention explicitly designed to reduce stigma as a barrier to testing by asking people to recruit anyone they know to testing, thus allowing them to avoid the potential for increased stigma and/or blame associated with direct risk partner recruitment, and helping to normalize openly discussing HIV among social networks. We examined baseline and 6-10-week follow-up data from a 2022-2023 randomized trial in KwaZulu-Natal, South Africa that recruited 110 individuals who had been newly diagnosed with HIV and randomly assigned them to recruit people to HIV testing either via the E-SNRHT intervention or via risk network recruitment. Participants in the E-SNRHT intervention reported significant decreases in anticipated and enacted HIV-related stigma between baseline and follow-up; and the E-SNRHT intervention was more effective at decreasing enacted HIV-related stigma than was risk network recruitment. Individuals newly diagnosed with HIV by the E-SNRHT intervention reported significant increases in social support between intervention enrollment and follow-up, and all of these individuals reported participating in positive conversations about HIV services with peers in the 6-10 weeks after intervention enrollment. These findings suggest that E-SNRHT is a potentially important strategy to reduce HIV-related stigma as a barrier to HIV testing among peer networks in KwaZulu-Natal.

Structural Discrimination against and Structural Support for Lesbian, Gay, and Bisexual People as a Predictor of Late HIV Diagnoses among Black Men who Have Sex with Men.

Black men who have sex with men (MSM) have been consistently reported to have the highest estimated HIV incidence and prevalence among MSM. Despite broad theoretical understanding that discrimination is a major social and structural determinant that contributes to disparate HIV outcomes among Black MSM, relatively little extant research has empirically examined structural discrimination against sexual minorities as a predictor of HIV outcomes among this population. The present study therefore examines whether variation in policies that explicitly discriminate against lesbian, gay, and bisexual (LGB) people and variation in policies that explicitly protect LGB people differentially predict metropolitan statistical-area-level variation in late HIV diagnoses among Black MSM over time, from 2008 to 2014. HIV surveillance data on late HIV diagnoses among Black MSM in each of the 95 largest metropolitan statistical areas in the United States, from 2008 to 2014, were used along with data on time-varying state-level policies pertaining to the rights of LGB people. Results from multilevel models found a negative relationship between protective/supportive laws and late HIV diagnoses among Black MSM, and a positive relationship between discriminative laws and late HIV diagnoses among Black MSM. These findings illuminate the potential epidemiological importance of policies pertaining to LGB populations as structural determinants of HIV outcomes among Black MSM. They suggest a need for scrutiny and elimination of discriminatory policies, where such policies are currently in place, and for advocacy for policies that explicitly protect the rights of LGB people where they do not currently exist.

Disentangling genetic and environmental influences on early language development: The interplay of genetic propensity for negative emotionality and surgency, and parenting behavior effects on early language skills in an adoption study.

Parenting and children's temperament are important influences on language development. However, temperament may reflect prior parenting, and parenting effects may reflect genes common to parents and children. In 561 U.S. adoptees (57% male) and their birth and rearing parents (70% and 92% White, 13% and 4% African American, and 7% and 2% Latinx, respectively), this study demonstrated how genetic propensity for temperament affects language development, and how this relates to parenting. Genetic propensity for negative emotionality inversely predicted language at 27 months (ß = -.15) and evoked greater maternal warmth (ß = .12), whereas propensity for surgency positively predicted language at 4.5 years (ß = .20), especially when warmth was low. Parental warmth (ß = .15) and sensitivity (ß = .19) further contributed to language development, controlling for common gene effects.

The pernicious role of stress on intergenerational continuity of psychopathology.

Development and Psychopathology has been a premier resource for understanding stressful childhood experiences and the intergenerational continuity of psychopathology. Building on that tradition, we examined the unique and joint influences of maternal stress on children's effortful control (age 7) and externalizing behavior (age 11) as transmitted via genetics, the prenatal environment, and the postnatal environment. The sample included N = 561 adopted children and their biological and adoptive parents. Path models identified a direct effect of biological mother life stress on children's effortful control (ß = -.08) and an indirect effect of her life stress on child externalizing behavior via effortful control (ß = .52), but no main or indirect effects of biological parent psychopathology, prenatal stress, or adoptive mother adverse childhood experiences (ACES). Adoptive mother ACES amplified the association between biological mother life stress and child effortful control (ß = -.08), externalizing behavior (ß = 1.41), and the indirect effect via effortful control, strengthening associations when adoptive mothers reported average or high ACES during their own childhoods. Results suggest that novel study designs are needed to enhance the understanding of how life stress gets "under the skin" to affect psychopathology in the offspring of adults who have experienced stress.

Unique influences of pregnancy and anticipated parenting on cigarette smoking: results and implications of a within-person, between-pregnancy study.

Not all pregnant individuals want to become parents and "parenting intention" can also vary within individuals during different pregnancies. Nevertheless, the potential impact of parenting intention on health-related behavior during pregnancy has been heavily underexplored. In this study, we employed a within-person between pregnancy design to estimate the effect of parenting-specific influences on smoking, separate from pregnancy-specific and individual-level influences. We quantified within-mother differences in smoking during pregnancies of infants they reared (n = 84) versus pregnancies of infants they placed for adoption at birth (n = 65) using multivariate mixed-effects Poisson regression models. Mean cigarettes/day declined as the pregnancy progressed regardless of whether infants were reared or placed. However, participants smoked fewer cigarettes/day during reared pregnancies. Relative to "adopted" pregnancies, smoking during "reared" pregnancies was lower by 24%, 41%, and 54% in first (95% CI 0.64-0.90; p = 0.001), second (95% CI 0.48-0.72; p < 0.001), and third trimesters (95% CI 0.36-0.59; p < 0.001), respectively, independent of between-pregnancy differences in maternal age, fetal sex, parity, and pregnancy complications. Female sex and nulliparity were protective. Parenting intention was associated with a protective effect on pregnancy smoking independent of pregnancy-specific influences and individual characteristics. Failure to consider the impact of parenting intention on health-related behavior during pregnancy could perpetuate an unrealistic expectation to "do what's best for the baby" and stigmatize women with unintended or unwanted pregnancies.

The role of fathers in child development from preconception to postnatal influences: Opportunities for the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program.

A growing body of literature highlights the important role of paternal health and socioemotional characteristics in child development, from preconception through adolescence. Much of this research addresses the indirect effects of fathers, for instance, their influence on maternal behaviors during the prenatal period or via the relationship with their partner. However, emerging evidence also recognizes the direct role of paternal health and behavior for child health and adjustment across development. This critical review presents evidence of biological and sociocultural influences of fathers on preconception, prenatal, and postnatal contributions to child development. The National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program incorporates in its central conceptualization the impact of fathers on family and child outcomes. This critical synthesis of the literature focuses on three specific child outcomes in the ECHO program: health outcomes (e.g., obesity), neurodevelopmental outcomes (e.g., emotional, behavioral, psychopathological development), and positive health. We highlight the unique insights gained from the literature to date and provide next steps for future studies on paternal influences.

Validation and measurement invariance of the Compulsive Exercise Test among Brazilian and American young adults.

PURPOSE: To evaluate compulsive exercise, researchers often rely on the widely used Compulsive Exercise Test (CET). However, the measure has shown unstable factor structure in several validation studies and is not available in Portuguese for use in Brazil. We aimed to describe the translation and cultural adaptation of the CET to Brazilian Portuguese, to test several factor structures among Brazilian and US samples of men and women, to test measurement invariance across countries, and to evaluate its internal consistency. Furthermore, we sought to evaluate convergent validity, correlating the CET with a measure of eating disorder symptoms, and to compare compulsive exercise symptoms between countries. METHODS: Four models of the latent structure of the CET were tested using confirmatory factor analyses (CFAs), three-factor structure with 15 items, three-factor structure with 18 items, four-factor structure with 21 items, and the original five-factor structure with 24 items, in a sample of 1,531 young adults (601 Brazilians and 930 Americans), aged 18-35 years. RESULTS: A series of CFAs demonstrated that the three-factor structure with 15 items showed a better fit to the data. This model demonstrated good convergent validity and internal consistency. Results from the CET multigroup CFA showed evidence for the invariance at the configural, metric, and scalar levels across Brazilians and Americans. Furthermore, significant differences were found between Brazilians and Americans, with Brazilians demonstrating higher scores on the Avoidance and rule-driven behavior and Mood improvement subscales, whereas US participants scored higher on the Weight control exercise subscale. CONCLUSIONS: Results support the three-factor structure with 15 items to be used as a measure of compulsive exercise among Brazilians and Americans, allowing cross-cultural comparisons between these countries. LEVEL OF EVIDENCE: Level V, Cross-sectional, Psychometric study.

Adolescent child custody loss and substance use treatment as predictors of young adult substance use trajectories among females with foster care and juvenile justice involvement.

This study aimed to identify trajectories of substance use from adolescence to young adulthood among 166 females with dual child welfare and juvenile justice system involvement, and to explore the influence of adolescent child custody status and substance use treatment on substance use trajectories. Results identified four substance use trajectory groups (stable moderate substance use, decreasing substance use, increasing substance use, stable high substance use). Custody loss during adolescence predicted membership in the stable high substance use trajectory group (log odds estimate = 2.99, p = < 0.01). No significant associations were found with adolescent substance use treatment. The findings can inform policymakers, foster care professionals, and law enforcement officers to promote the delivery of timely and appropriate substance use services that respond to the unique needs of females across the child welfare and juvenile justice system populations.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P < .001, d = .16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles.

Allelopathy-selected microbiomes mitigate chemical inhibition of plant performance.

Allelopathy is a common and important stressor that shapes plant communities and can alter soil microbiomes, yet little is known about the direct effects of allelochemical addition on bacterial and fungal communities or the potential for allelochemical-selected microbiomes to mediate plant performance responses, especially in habitats naturally structured by allelopathy. Here, we present the first community-wide investigation of microbial mediation of allelochemical effects on plant performance by testing how allelopathy affects soil microbiome structure and how these microbial changes impact germination and productivity across 13 plant species. The soil microbiome exhibited significant changes to 'core' bacterial and fungal taxa, bacterial composition, abundance of functionally important bacterial and fungal taxa, and predicted bacterial functional genes after the addition of the dominant allelochemical native to this habitat. Furthermore, plant performance was mediated by the allelochemical-selected microbiome, with allelopathic inhibition of plant productivity moderately mitigated by the microbiome. Through our findings, we present a potential framework to understand the strength of plant-microbial interactions in the presence of environmental stressors, in which frequency of the ecological stress may be a key predictor of microbiome-mediation strength.

Creation and Validation of a New Socio-built Environment Index Measure of Opioid Overdose Risk for Use in Both Non-urban and Urban Settings.

A great deal of literature has examined features of the physical built environment as predictors of opioid overdose and other substance use-related outcomes. Other literature suggests that social characteristics of settings are important predictors of substance use outcomes. However, there is a dearth of literature simultaneously measuring both physical and social characteristics of settings in an effort to better predict opioid overdose. There is also a dearth of literature examining built environment as a predictor of overdose in non-urban settings. The present study presents a novel socio-built environment index measure of opioid overdose risk comprised of indicators measuring both social and physical characteristics of settings - and developed for use in both urban and non-urban settings - and assesses its validity among 565 urban, suburban, and rural New Jersey municipalities. We found that this novel measure had good convergent validity, based on significant positive associations with a social vulnerability index and crime rates, and significant negative associations with a municipal revitalization index and high school graduation rates. The index measure had good discriminant validity, based on lack of association with three different racial isolation indices. Finally, our index measure had good health outcome-based criterion validity, based on significant positive associations with recent overdose mortality. There were no major differences between rural, suburban, and urban municipalities in validity analysis findings. This promising new socio-built environment risk index measure could improve ability to target and allocate resources to settings with the greatest risk, in order to improve their impact on overdose outcomes.