The ADAPT Parenting Intervention Benefits Combat Exposed Fathers Genetically Susceptible to Problem Drinking.

Testing a vantage sensitivity model from differential susceptibility theory (DST), we examined a G × E × I hypothesis; that is, whether a military parenting intervention program (I) might buffer a G × E susceptibility for military deployed fathers exposed to deployment combat stress and trauma. We hypothesized that combat stress (E, referring to the natural environmental factor) would lead to increases in problem drinking, and that the effect of problem drinking would be amplified by genetic predisposition (G) for drinking reward systems, substance use, and addictive behaviors (i.e., differential vulnerability). Providing a preventive intervention designed to improve post-deployment family environments (I, vantage sensitivity) is hypothesized to buffer the negative impacts of combat exposure and genetic susceptibility. The sample included 185 post-deployed military fathers who consented to genotyping, from a larger sample of 294 fathers enrolled in a randomized effectiveness trial of the After Deployment Adaptive Parenting Tools (ADAPT) intervention. Trauma-exposed military fathers at genetic susceptibility for problem drinking assigned to the ADAPT intervention reported significantly more reductions in risky drinking compared with fathers at genetic susceptibility assigned to the control group, with a small effect size for the G × E × I interaction (d = .2). Trial Registration. The ADAPT trial is registered at the US National Institutes of Health ( ClinicalTrials.gov ) # NCT03522610.

Reaching Latinx Communities with Algorithmic Optimization for SARS-CoV-2 Testing Locations.

The COVID-19 pandemic has disproportionately affected communities of color, including Latinx communities. Oregon Saludable: Juntos Podemos (OSJP) is a randomized clinical trial aimed at reducing this disparity by both increasing access to testing for SARS-CoV-2, the virus that causes COVID-19, for Oregon Latinx community members and studying the effectiveness of health and behavioral health interventions on turnout and health outcomes. OSJP established SARS-CoV-2 testing events at sites across Oregon. A critical early question was how to locate these sites to best serve Latinx community members. To propose sites in each participating county, we implemented an algorithmic approach solving a facilities location problem. This algorithm was based on minimizing driving time from Latinx population centers to SARS-CoV-2 testing locations. OSJP staff presented these proposed testing locations to community partners as a starting place for identifying final testing sites. Due to differences in geography, population distributions, and potential site accessibility, the study sites exhibited variation in how well the algorithmic optimization objectives could be satisfied. From this variation, we inferred the effects of the drive time optimization metric on the likelihood of Latinx community members utilizing SARS-CoV-2 testing services. After controlling for potential confounders, we found that minimizing the drive time optimization metric was strongly correlated with increased turnout among Latinx community members. This paper presents the algorithm and data sources used for site proposals and discusses challenges and opportunities for community-based health promotion research when translating algorithm proposals into action across a range of health outcomes.

Framing the discussion of microorganisms as a facet of social equity in human health.

What do "microbes" have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the "health" of the environments we build. The loss, gain, and retention of microorganisms-their flow between humans and the environment-can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure.

Risk alleles for tuberculosis infection associate with reduced immune reactivity in a wild mammalian host.

Integrating biological processes across scales remains a central challenge in disease ecology. Genetic variation drives differences in host immune responses, which, along with environmental factors, generates temporal and spatial infection patterns in natural populations that epidemiologists seek to predict and control. However, genetics and immunology are typically studied in model systems, whereas population-level patterns of infection status and susceptibility are uniquely observable in nature. Despite obvious causal connections, organizational scales from genes to host outcomes to population patterns are rarely linked explicitly. Here we identify two loci near genes involved in macrophage (phagocyte) activation and pathogen degradation that additively increase risk of bovine tuberculosis infection by up to ninefold in wild African buffalo. Furthermore, we observe genotype-specific variation in IL-12 production indicative of variation in macrophage activation. Here, we provide measurable differences in infection resistance at multiple scales by characterizing the genetic and inflammatory variation driving patterns of infection in a wild mammal.

Host genomic variation shapes gut microbiome diversity in threespine stickleback fish.

IMPORTANCE: A major focus of host-microbe research is to understand how genetic differences, of various magnitudes, among hosts translate to differences in their microbiomes. This has been challenging for animal hosts, including humans, because it is difficult to control environmental variables tightly enough to isolate direct genetic effects on the microbiome. Our work in stickleback fish is a significant contribution because our experimental approach allowed strict control over environmental factors, including standardization of the microbiome from the earliest stage of development and unrestricted co-housing of fish in a truly common environment. Furthermore, we measured host genetic variation over 2,000 regions of the stickleback genome, comparing this information and microbiome composition data among fish from very similar and very different genetic backgrounds. Our findings highlight how differences in the host genome influence microbiome diversity and make a case for future manipulative microbiome experiments that use host systems with naturally occurring genetic variation.

COVID-19 vaccine deliberation among people who inject drugs.

Background: People who inject drugs (PWID) are at greater risk for severe morbidity and mortality associated with COVID-19 due to comorbid, chronic, medical conditions and structural inequities associated with housing instability and incarceration. As such, they are a population that would greatly benefit from COVID-19 vaccination. Methods: We surveyed 350 syringe exchange clients between March 2021 and June 2021 to collect information on vaccine uptake among PWID, facilitators and barriers to vaccination, and demographic correlates of vaccine hesitancy. Results: Findings highlight that among PWID, vaccination access was remarkably low with only 10% of the sample receiving a COVID-19 vaccine. Vaccine acceptability among people who were vaccinated was 42% highlighting barriers to access. Motivation for vaccination included a desire to keep family members and other community members safe and a desire to feel safe around other people. Barriers to vaccination included concerns about vaccine side effects, lack of concern surrounding the effects of COVID-19, and insufficient information about how the vaccine works, along with general distrust of the vaccine development and deployment process. Conclusions: There is a need for structural interventions and individual behavioral interventions to improve COVID-19 vaccine access and uptake among PWID. Limitations and implications for next steps and future directions are discussed.

Contingency Management and SARS-CoV-2 Testing Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are especially vulnerable to morbidity and mortality as a result of SARS-CoV-2 infection because of social and physical health vulnerabilities. Routine testing for SARS-CoV-2 is critical to reduce transmission. Contingency management-the provision of tangible rewards to reinforce positive behavior-can promote the use of health services among PWID. Evidence is scarce on the utility of contingency management to promote SARS-CoV-2 testing. The objective of this study was to evaluate the effectiveness of contingency management to increase testing among PWID. METHODS: SARS-CoV-2 testing was implemented at 9 syringe exchange program sites in partnership with an Oregon-based nonprofit organization for 5 weeks without contingency management and for 6 weeks with contingency management (a $10 financial incentive for testing) from February 1 through mid-April 2021. We measured rates of testing among syringe exchange program clients before and after implementation of contingency management. RESULTS: Before contingency management, SARS-CoV-2 testing occurred during approximately 131 of 1410 (9.3%) client encounters, and 123 of 997 (12.3%) unique clients were tested. During contingency management, testing occurred during approximately 571 of 1756 (32.5%) client encounters, and 407 of 1151 (35.4%) unique clients were tested. Rates of testing increased from 0.04 (SD, 0.04) before contingency management implementation to 0.25 (SD, 0.15) after implementation (t8 = -3.88; P = .005; Cohen d = 1.46). CONCLUSIONS: Contingency management facilitated uptake of SARS-CoV-2 testing among PWID. Contingency management may be an effective strategy for improving communicable disease testing beyond testing for SARS-CoV-2 and for improving vaccine uptake among PWID and warrants additional research.

Effectiveness of a COVID-19 Testing Outreach Intervention for Latinx Communities: A Cluster Randomized Trial.

Importance: Latinx individuals have been disproportionately affected during the COVID-19 pandemic caused by the spread of SARS-CoV-2. It is imperative to evaluate newly developed preventive interventions to assess their effect on COVID-19 health disparities. Objective: To examine the effectiveness of a culturally tailored outreach intervention designed to increase SARS-CoV-2 testing rates among Latinx populations. Design, Setting, and Participants: In this cluster randomized trial performed from February 1 to August 31, 2021, in community settings in 9 Oregon counties, 38 sites were randomized a priori (19 to the community health promoters intervention and 19 to outreach as usual wait-listed controls). Thirty-three sites were activated. A total of 394 SARS-CoV-2 testing events were held and 1851 diagnostic samples collected, of which 919 were from Latinx persons. Interventions: A culturally informed outreach program was developed that made use of promotores de salud (community health promoters) to increase Latinx SARS-CoV-2 testing. Strategies addressed barriers by disseminating information on testing events in English and Spanish, mitigating misinformation, and increasing trust. Main Outcomes and Measures: The primary outcomes were the count of sample tests from Latinx persons and the sampled proportion of the Latinx populace. Site-level covariates included census tract Latinx populace, nativity (number of US-born individuals per 100 population), median age, and income inequality. Time-varying covariates included number of new weekly SARS-CoV-2-positive cases and percentage of vaccine coverage at the county level. Results: A total of 15 clusters (sites) were randomized to the control group and 18 to the community health promoters group. A total of 1851 test samples were collected, of which 995 (53.8%) were from female participants and 919 (49.6%) were from Latinx individuals. The intervention tested 3.84 (95% CI, 2.47-5.97) times more Latinx individuals per event than controls (incident rate ratio, 0.79; 95% CI, 0.46-1.34; Cohen d = 0.74; P < .001). The intervention was associated with a 0.28 increase in the proportion of Latinx populace being tested compared with control sites for the dependent variable scaled as the proportion of the Latinx populace ×100, or a 0.003 proportion of the raw populace count. The use of a standardized scaling of the proportion of Latinx individuals showed that the relative percentage increase was 0.53 (95% CI, 0.21-0.86) in the intervention sites compared with controls, representing a medium effect size. Conclusions and Relevance: To our knowledge, this was the first randomized evaluation of an outreach intervention designed to increase SARS-CoV-2 testing among Latinx populations. Findings could be used to implement strategies to reduce other health disparities experienced by these groups. Trial Registration: ClinicalTrials.gov Identifier: NCT04793464.

Shared Environment and Genetics Shape the Gut Microbiome after Infant Adoption.

The composition of the human gut microbiome is highly variable, and this variation has been repeatedly tied to variation in human health. However, the sources of microbial variation remain unclear, especially early in life. It is particularly important to understand sources of early life variation in the microbiome because the state of the microbiome in childhood can influence lifelong health. Here, we compared the gut microbiomes of children adopted in infancy to those of genetically unrelated children in the same household and genetically related children raised in other households. We observed that a shared home environment was the strongest predictor of overall microbiome similarity. Among those microbial taxa whose variation was significantly explained by our models, the abundance of a given taxon was more frequently explained by host genetic similarity (relatedness), while the presence of a given taxon was more dependent upon a shared home environment. This suggests that although the home environment may act as a species source pool for the gut microbiome in childhood, host genetic factors likely drive variation in microbial abundance once a species colonizes the gut.IMPORTANCE Our results demonstrate that the early life home environment can significantly alter the gut microbiome in childhood, potentially altering health outcomes or risk for adverse health outcomes. A better understanding of the drivers of gut microbiome variation during childhood could lead to more effective intervention strategies for overall health starting in early life.

History of breastfeeding but not mode of delivery shapes the gut microbiome in childhood.

BACKGROUND: The naïve neonatal gut is sensitive to early life experiences. Events during this critical developmental window may have life-long impacts on the gut microbiota. Two experiences that have been associated with variation in the gut microbiome in infancy are mode of delivery and feeding practices (eg, breastfeeding). It remains unclear whether these early experiences are responsible for microbial differences beyond toddlerhood. AIMS: Our study examined whether mode of delivery and infant feeding practices are associated with differences in the child and adolescent microbiome. DESIGN, SUBJECTS, MEASURES: We used an adoption-sibling design to compare genetically related siblings who were reared together or apart. Gut microbiome samples were collected from 73 children (M = 11 years, SD = 3 years, range = 3-18 years). Parents reported on child breastfeeding history, age, sex, height, and weight. Mode of delivery was collected through medical records and phone interviews. RESULTS: Negative binomial mixed effects models were used to identify whether mode of delivery and feeding practices were related to differences in phylum and genus-level abundance of bacteria found in the gut of child participants. Covariates included age, sex, and body mass index. Genetic relatedness and rearing environment were accounted for as random effects. We observed a significant association between lack of breastfeeding during infancy and a greater number of the genus Bacteroides in stool in childhood and adolescence. CONCLUSION: The absence of breastfeeding may impart lasting effects on the gut microbiome well into childhood.

Using a sibling-adoption design to parse genetic and environmental influences on children's body mass index (BMI).

Dietary and physical activity behaviors formed early in life can increase risk for childhood obesity and have continued negative consequences for lifelong health. Previous research has highlighted the importance of both genetic and environmental (e.g., cultural environment or parental lifestyle) contributions to obesity risk, although these studies typically involve genetically-related individuals residing in the same household, where genetic similarity and rearing environment are inextricably linked. Here we utilize a sibling-adoption design to independently estimate genetic and environmental contributions to obesity risk in childhood and describe how these influences might vary as children age. As part of a prospective adoption study, the current investigation used data from biological siblings reared either apart or together, and nonbiological siblings reared together to estimate the contributions of genetics and environment to body mass indices (BMI) in a large cohort of children (N = 711). We used a variance partitioning model to allocate variation in BMI to that which is due to shared genetics, common environment, or unique environment in this cohort during middle childhood and adolescence. We found 63% of the total variance in BMI could be attributed to heritable factors in middle childhood sibling pairs (age 5-11.99; 95% CI [0.41,0.85]). Additionally, we observed that common environment explained 31% of variation in BMI in this group (95% CI [0.11,0.5]), with unique environment and error explaining the remaining variance. We failed to detect an influence of genetics or common environment in older sibling pairs (12-18) or pairs spanning childhood and adolescence (large sibling age difference), but home type (adoptive versus birth) was an important predictor of BMI in adolescence. The presence of strong common environment effects during childhood suggests that early interventions at the family level in middle childhood could be effective in mitigating obesity risk in later childhood and adolescence.

Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host.

Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as "infection resistance," in which hosts delay or prevent infection, and "proliferation resistance," in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h 2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a "fast" pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health-such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population.

Genotypic variation in host response to infection affects parasite reproductive rate.

Parasite fitness is largely influenced by a variation in host response due to the host's genetic background. Here we investigated the impact of host genotype on pathogen success in the snail vector of its castrating parasite, Schistosoma mansoni. We infected five inbred lines of Biomphalaria glabrata with two infection doses and followed their growth, reproductive output and parasite production throughout the course of infection. There was no difference in resistance to infection among inbred lines, but lines varied in their responses to infection and the numbers of parasites produced. Snails did not compensate for castration by increasing their fecundity during the early phase of infection (fecundity compensation). However, some lines were able to delay parasite shedding for up to 30 weeks, thus prolonging reproduction before the onset of castration. Here we propose this strategy as a novel defense against castrating pathogens in snails. Gigantism, a predicted outcome of castration due to energy reallocation, occurred early in infection (<15 weeks) and was not universal among the snail lines. Lines that did not show gigantism were also characterised by a high parasite production rate and low survivorship, perhaps indicating energy reallocation into parasite production and costly immune defense. We observed no differences in total parasite production among lines throughout the entire course of infection, although lines differed in their parasite reproductive rate. The average rate of parasite production varied among lines from 1300 to 2450 cercariae within a single 2h shedding period, resulting in a total production of 6981-29,509 cercariae over the lifetime of a single snail. Regardless of genetic background, snail size was a strong predictor of parasite reproduction: each millimetre increase in snail size at the time of the first shed resulted in up to 3500 more cercariae over the lifetime of the snail. The results of this study provide a detailed picture of variation in hosts' responses to infection and the resulting impacts on parasite fitness, further defining the intricacies of snail-schistosome compatibility.

Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni.

BACKGROUND: New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails. METHODOLOGY/PRINCIPAL FINDINGS: Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2 Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated. CONCLUSIONS/SIGNIFICANCE: The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation.

Hybridization, cryptic diversity, and invasiveness in introduced variable-leaf watermilfoil.

Hybridization may be important in the evolution of invasiveness, but few empirical studies compare introduced hybrid and parental lineages. Invasive 'variable-leaf watermilfoil' (Myriophyllum heterophyllum) in the northeastern United States consists of at least three distinct lineages: an interspecific hybrid (M. heterophyllum × Myriophyllum laxum) and two historically allopatric lineages of pure M. heterophyllum. Previous observations suggested that hybrid populations of variable-leaf watermilfoil may be comparatively more 'invasive' than pure lineages. However, no quantitative data comparing hybrid and parental lineages have been collected, nor has invasiveness been compared between parental lineages. Here, we demonstrate that these distinct lineages are also ecologically distinct. We find some support for the hypothesis that hybridization has played a role in the evolution of invasiveness: hybrids exhibited higher biomass, individual plant size, and greater branching than at least one parental lineage of M. heterophyllum. However, parental lineages did not differ from the hybrid for some traits, demonstrating that pure parental lineages can also be invasive. In addition, we found no evidence for a role of intraspecific hybridization in the evolution of invasiveness in these lineages of variable-leaf watermilfoil, even where they co-occurred locally. Our study suggests that distinguishing among cryptic lineages will help prioritize rapid response control efforts.