Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota.

Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous diversification of memory B cells constitutes a central process for establishing symbiotic host-microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn.

Neurotoxic reactive astrocytes induce cell death via saturated lipids.

Astrocytes regulate the response of the central nervous system to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease1-6. Here we report an approach to isolate one component of the long-sought astrocyte-derived toxic factor5,6. Notably, instead of a protein, saturated lipids contained in APOE and APOJ lipoparticles mediate astrocyte-induced toxicity. Eliminating the formation of long-chain saturated lipids by astrocyte-specific knockout of the saturated lipid synthesis enzyme ELOVL1 mitigates astrocyte-mediated toxicity in vitro as well as in a model of acute axonal injury in vivo. These results suggest a mechanism by which astrocytes kill cells in the central nervous system.

Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma.

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.

Person-Centered Models for Cardiovascular Care: A Review of the Evidence: A Scientific Statement From the American Heart Association.

Cardiovascular disease remains the leading cause of death and disability in the United States and globally. Disease burden continues to escalate despite technological advances associated with improved life expectancy and quality of life. As a result, longer life is associated with multiple chronic cardiovascular conditions. Clinical guidelines provide recommendations without considering prevalent scenarios of multimorbidity and health system complexities that affect practical adoption. The diversity of personal preferences, cultures, and lifestyles that make up one's social and environmental context is often overlooked in ongoing care planning for symptom management and health behavior support, hindering adoption and compromising patient outcomes, particularly in groups at high risk. The purpose of this scientific statement was to describe the characteristics and reported outcomes in existing person-centered care delivery models for selected cardiovascular conditions. We conducted a scoping review using Ovid MEDLINE, Embase.com, Web of Science, CINAHL Complete, Cochrane Central Register of Controlled Trials through Ovid, and ClinicalTrials.gov from 2010 to 2022. A range of study designs with a defined aim to systematically evaluate care delivery models for selected cardiovascular conditions were included. Models were selected on the basis of their stated use of evidence-based guidelines, clinical decision support tools, systematic evaluation processes, and inclusion of the patient's perspective in defining the plan of care. Findings reflected variation in methodological approach, outcome measures, and care processes used across models. Evidence to support optimal care delivery models remains limited by inconsistencies in approach, variation in reimbursement, and inability of health systems to meet the needs of patients with chronic, complex cardiovascular conditions.

Popular Dietary Patterns: Alignment With American Heart Association 2021 Dietary Guidance: A Scientific Statement From the American Heart Association.

The evolution of dietary guidelines from isolated nutrients to broader dietary pattern recommendations results from growing knowledge of the synergy between nutrients and their food sources as they influence health. Macronutrient and micronutrient needs can be met by consuming various dietary patterns, but guidance is often required to facilitate population-wide adherence to wise food choices to achieve a healthy dietary pattern. This is particularly true in this era with the proliferation of nutrition misinformation and misplaced emphasis. In 2021, the American Heart Association issued a scientific statement outlining key principles of a heart-healthy dietary pattern that could be operationalized in various ways. The objective of this scientific statement is to assess alignment of commonly practiced US dietary patterns with the recently published American Heart Association criteria, to determine clinical and cultural factors that affect long-term adherence, and to propose approaches for adoption of healthy dietary patterns. This scientific statement is intended to serve as a tool for clinicians and consumers to evaluate whether these popular dietary pattern(s) promote cardiometabolic health and suggests factors to consider when adopting any pattern to improve alignment with the 2021 American Heart Association Dietary Guidance. Numerous patterns strongly aligned with 2021 American Heart Association Dietary Guidance (ie, Mediterranean, DASH [Dietary Approaches to Stop Hypertension], pescetarian, vegetarian) can be adapted to reflect personal and cultural preferences and budgetary constraints. Thus, optimal cardiovascular health would be best supported by developing a food environment that supports adherence to these patterns wherever food is prepared or consumed.

Variety of High and Very Low-Energy Density Foods among Preschool-Aged Children and Associations with Food Intake, Diet Quality, and Weight Status.

BACKGROUND: Energy density (ED) and the variety of foods are 2 factors that may have a combined effect on preschool-aged children's ability to regulate food intake. However, little is known about the variety of foods consumed within different ED categories by children in the United States. OBJECTIVE: Therefore, we explored the variety of high ED (HED, 4-9 kcal/g) and very low ED (VLED, <0.6 kcal/g) foods consumed by a nationally representative sample of children aged 2-5 y in the United States and the relationship between variety with food intake, diet quality, and weight status. METHODS: ED, variety, and diet quality were assessed using two 24-h dietary recalls collected as part of the National Health And Nutrition Examination Survey 2011-2018 cycles (n = 1682). We assessed associations between HED and VLED varieties with energy intake, volume of food, diet quality, and weight status using multivariable linear and logistic regressions. RESULTS: The HED variety was positively associated with energy intake (P < 0.0001). The VLED variety was positively associated with the volume of food (P < 0.0001) and diet quality (P < 0.0001). VLED was negatively associated with the odds of having obesity in minimally adjusted models [odds ratio (OR): 0.62; 95% confidence interval (CI): 0.31, 0.87]; however, the relationship was not significant in fully adjusted models. Patterns of variety intake were differently associated with energy, volume, and diet quality. Children consuming the high VLED variety and the low HED variety had lower odds of obesity [OR: 0.43; 95% CI: 0.21, 0.90]; however, this pattern was rare (10%). CONCLUSIONS: These findings suggest that the variety of HED foods is associated with higher average energy intake per day, and the variety of VLED foods is associated with a higher volume of food consumed per day and diet quality in a nationally representative sample of preschool-aged children.

BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity.

The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

SIGNIFICANCE STATEMENT: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.0% of them. We detected no significant differences in the overall diagnostic yield among COU subphenotypes, with characteristic variable expressivity of several mutant genes. Our findings therefore may legitimize a genetic first diagnostic approach for COU, especially when burdening clinical and imaging characterization is not complete or available. BACKGROUND: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. METHODS: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction ( n =321), ureterovesical junction obstruction/congenital megaureter ( n =178), and COU not otherwise specified (COU-NOS; n =234). RESULTS: We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders (GDs) in 23 (3.1%) cases. We detected no significant differences in the overall diagnostic yield between COU sub-phenotypes, and pathogenic SNVs in several genes were associated to any of the three categories. Hence, although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. On the other hand, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and GDs suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU. CONCLUSIONS: We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis.

Constructing Antiretroviral Supramolecular Polymers as Long-Acting Injectables through Rational Design of Drug Amphiphiles with Alternating Antiretroviral-Based and Hydrophobic Residues.

One of the main challenges in the development of long-acting injectables for HIV treatment is the limited duration of drug release, which results in the need for frequent dosing and reduced patient adherence. In this context, we leverage the intrinsic reversible features of supramolecular polymers and their unique ability to form a three-dimensional network under physiological conditions to design a class of self-assembling drug amphiphiles (DAs) based upon lamivudine, a water-soluble antiretroviral (ARV) agent and nucleoside reverse transcriptase inhibitor. The designed ARV DAs contain three pairs of alternating hydrophobic valine (V) and hydrophilic lamivudine-modified lysine (K3TC) residues with a varying number of glutamic acids (E) placed on the C-terminus. Upon dissolution in deionized water, all three ARV DAs were found to spontaneously associate into supramolecular filaments of several micrometers in length, with varying levels of lateral stacking. Addition of 1× PBS triggered immediate gelation of the two ARV DAs with 2 or 3 E residues, and upon dilution in an in vitro setting, the dissociation from the supramolecular state to the monomeric state enabled a long-acting linear release of the ARV DAs. In vivo studies further confirmed their injectability, rapid in situ hydrogel formation, enhanced local retention, and long-acting therapeutic release over a month. Importantly, our pharmacokinetic studies suggest that the injected ARV supramolecular polymeric hydrogel was able to maintain a plasma concentration of lamivudine above its IC50 value for more than 40 days in mice and showed minimal systemic immunogenicity. We believe that these results shed important light on the rational design of long-acting injectables using the drug-based molecular assembly strategy, and the reported ARV supramolecular hydrogels hold great promise for improving HIV treatment outcomes.

The Geography of Sexual Conflict: A Synthetic Review.

AbstractSexual conflict is a mechanism of selection driven by the divergent fitness interests between females and males. This disagreement can be great enough to promote antagonistic/defensive traits and behaviors. Although the existence of sexual conflict has been identified in many species, less research has explored the conditions that initially promote sexual conflict in animal mating systems. In previous work in Opiliones, we observed that morphological traits associated with sexual conflict occurred only in species from northern localities. We hypothesized that by shortening and compartmentalizing time periods optimal for reproduction, seasonality represents a geographic condition sufficient to promote sexual conflict. We conducted a systematic review of the literature on reproductive traits and behaviors. Using standardized criteria, we reviewed publications to identify whether subjects occurred in a temperate (high-seasonality) or tropical (low-seasonality) biome. After identifying and adjusting for a publication bias toward temperate research, we identified no significant difference in the strength of sexual conflict between temperate and tropical study systems. A comparison between the distribution of taxa studied in sexual conflict articles and articles focused on general biodiversity indicates that species with conflict-based mating systems more accurately represent the distribution of terrestrial animal species. These findings contribute to ongoing efforts to characterize the origins of sexual conflict as well as life history traits that covary with sexual conflict.

Human papillomaviruses: Knowns, mysteries, and unchartered territories.

There has been an explosion in the number of papillomaviruses that have been identified and fully sequenced. Yet only a minute fraction of these has been studied in any detail. Most of our molecular research efforts have focused on the E6 and E7 proteins of "high-risk," cancer-associated human papillomaviruses (HPVs). Interactions of the high-risk HPV E6 and E7 proteins with their respective cellular targets, the p53 and the retinoblastoma tumor suppressors, have been investigated in minute detail. Some have thus questioned if research on papillomaviruses remains an exciting and worthwhile area of investigation. However, fundamentally new insights on the biological activities and cellular targets of the high-risk HPV E6 and E7 proteins have been discovered and previously unstudied HPVs have been newly associated with human diseases. HPV infections continue to be an important cause of human morbidity and mortality and since there are no antivirals to combat HPV infections, research on HPVs should remain attractive to new investigators and biomedical funding agencies, alike.

Participant Characteristics Associated with High Responsiveness to Personalized Healthy Food Incentives: a Secondary Analysis of the Randomized Controlled Crossover Smart Cart Study.

BACKGROUND: Personalized dietary behavioral interventions could be enhanced by understanding factors accounting for individual variability in dietary decisions. OBJECTIVE: This study was a secondary analysis of the Smart Cart randomized controlled trial to determine whether participant characteristics predicted high responsiveness to personalized grocery incentives for purchasing healthy food. METHODS: This secondary analysis of a 9-mo crossover study included 192 regular shoppers (86%) from a Rhode Island supermarket. To analyze whether health, behavioral, and/or sociodemographic characteristics predicted responsiveness to a personalized grocery incentive intervention, participants were divided into 3 categories [high (n = 47), moderate (n = 50), and unresponsive (n = 95)] based on percentage changes in their Grocery Purchase Quality Index scores during the intervention versus control period calculated from sales data. We tested whether participant characteristics, including individual, household, and intervention-related factors, differed across responsiveness groups using ANOVA and whether they predicted the likelihood of being high responsive versus unresponsive or moderate responsive using logistic regression. RESULTS: Participants had a mean (SD) age of 56.0 (13.8) y and were 89% female. Education, self-reported BMI, income, diet-related medical condition, food insecurity, cooking adequacy, and value consciousness differed across responsiveness categories (P < 0.1). High versus moderate and unresponsive participants increased their percentage of spending on targeted foods (P < 0.0001) and purchased fewer unique items (P = 0.01). In multinomial adjusted models, the odds of being high versus unresponsive or moderate responsive were lower for participants with a BMI (in kg/m2) <25 versus ≥25 (OR: 0.41; 95% CI: 0.19, 0.90) and higher with a diet-related medical condition present (OR: 3.75; 95% CI: 1.20, 11.8). Other characteristics were not associated with responsiveness. CONCLUSIONS: Findings demonstrated that a BMI ≥25 and having a diet-related medical condition within the household predicted high responsiveness to a personalized grocery purchasing intervention, suggesting that personalized dietary interventions may be particularly effective for households with higher health risk. This trial is registered at www.clinicaltrials.gov as NCT03748056.

Evaluating niche changes during invasion with seasonal models in Capsella bursa-pastoris.

PREMISE: Researchers often use ecological niche models to predict where species might establish and persist under future or novel climate conditions. However, these predictive methods assume species have stable niches across time and space. Furthermore, ignoring the time of occurrence data can obscure important information about species reproduction and ultimately fitness. Here, we assess compare ecological niche models generated from full-year averages to seasonal models. METHODS: In this study, we generate full-year and monthly ecological niche models for Capsella bursa-pastoris in Europe and North America to see if we can detect changes in the seasonal niche of the species after long-distance dispersal. RESULTS: We find full-year ecological niche models have low transferability across continents and there are continental differences in the climate conditions that influence the distribution of C. bursa-pastoris. Monthly models have greater predictive accuracy than full-year models in cooler seasons, but no monthly models can predict North American summer occurrences very well. CONCLUSIONS: The relative predictive ability of European monthly models compared to North American monthly models suggests a change in the seasonal timing between the native range to the non-native range. These results highlight the utility of ecological niche models at finer temporal scales in predicting species distributions and unmasking subtle patterns of evolution.

In-person versus online delivery of a behavioral sleep intervention (Sleeping Sound©) for children with ADHD: protocol for a parallel-group, non-inferiority, randomized controlled trial.

BACKGROUND: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) often experience sleep difficulties such as difficulty initiating and maintaining sleep. Problem sleep may impact children's daily functioning and behaviors and exacerbate ADHD symptoms. Most effective behavioral interventions to improve sleep are conducted in person, limiting accessibility to treatment for individuals in remote or rural communities or those who are unable to attend a clinic. This trial aims to assess the efficacy of delivering an established behavioral intervention online, Sleeping Sound with ADHD©, compared to a face-to-face delivery mode. METHODS: This parallel group, non-inferiority, randomized controlled trial (RCT) will include at least 68 children, aged 5-12 years old with ADHD. Families of children will be recruited from private developmental and psychological clinics and social media, within the state of Western Australia (WA). Once written informed consent and baseline questionnaires are completed, families are randomized to receive the behavioral intervention either in-person or online via Telehealth services. The intervention targets the assessment and management of reported sleep problems, through two individual consultations and a follow-up phone call with a trained clinician. The sleep outcomes assessed consist of a parent-reported sleep questionnaire and actigraphy. DISCUSSION: To the best of our knowledge, this is the first RCT to investigate sleep treatment modality for children with ADHD. If effective, clinicians can provide an evidence-based sleep intervention in an accessible manner. TRIAL REGISTRATION: ANZCTR, ACTRN12621001681842 . Registered 9 December 2021-Retrospectively registered.

Diagnostic Utility of Exome Sequencing for Kidney Disease.

BACKGROUND: Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS: We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS: In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS: Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.).

Strategies for managing marine disease.

The incidence of emerging infectious diseases (EIDs) has increased in wildlife populations in recent years and is expected to continue to increase with global environmental change. Marine diseases are relatively understudied compared with terrestrial diseases but warrant parallel attention as they can disrupt ecosystems, cause economic loss, and threaten human livelihoods. Although there are many existing tools to combat the direct and indirect consequences of EIDs, these management strategies are often insufficient or ineffective in marine habitats compared with their terrestrial counterparts, often due to fundamental differences between marine and terrestrial systems. Here, we first illustrate how the marine environment and marine organism life histories present challenges and opportunities for wildlife disease management. We then assess the application of common disease management strategies to marine versus terrestrial systems to identify those that may be most effective for marine disease outbreak prevention, response, and recovery. Finally, we recommend multiple actions that will enable more successful management of marine wildlife disease emergencies in the future. These include prioritizing marine disease research and understanding its links to climate change, improving marine ecosystem health, forming better monitoring and response networks, developing marine veterinary medicine programs, and enacting policy that addresses marine and other wildlife diseases. Overall, we encourage a more proactive rather than reactive approach to marine wildlife disease management and emphasize that multidisciplinary collaborations are crucial to managing marine wildlife health.

α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG4.

BACKGROUND: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. OBJECTIVE: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. METHODS: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. RESULTS: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. CONCLUSIONS: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

Structural Bases of Prion Variation in Yeast.

Amyloids are protein aggregates with a specific filamentous structure that are related to a number of human diseases, and also to some important physiological processes in animals and other kingdoms of life. Amyloids in yeast can stably propagate as heritable units, prions. Yeast prions are of interest both on their own and as a model for amyloids and prions in general. In this review, we consider the structure of yeast prions and its variation, how such structures determine the balance of aggregated and soluble prion protein through interaction with chaperones and how the aggregated state affects the non-prion functions of these proteins.

RNA electroelution: Comparing two electroeluter models.

RNA represents a vibrant area of research and many studies use techniques that require large amounts of purified RNA. One common purification method involves slicing a section of a polyacrylamide gel containing the RNA of interest and eluting the RNA out of the gel using electroelution. Various electroeluter models are available but sometimes a given model becomes discontinued, compelling researchers to choose a different model. Here, we have compared two electroeluters with different chamber designs for their ability to recover RNA from gel pieces. Our results show that both electroeluters are effective and recover comparable amounts of purified RNA.

Contributions of Food Environments to Dietary Quality and Cardiovascular Disease Risk.

PURPOSE OF REVIEW: To evaluate the multidimensional influence of food environments on food choice, dietary quality, and diet-related health and identify critical gaps necessary to develop effective population interventions that influence food choice. RECENT FINDINGS: Multicomponent interventions that interact with multiple layers of the food environment show limited but consistent effects on dietary behaviors and may have wider and substantive population-level reach with greater incorporation of validated, holistic measurement tools. Opportunities to use smartphone technology to measure multiple components of the food environment will facilitate future interventions, particularly as food environments expand into online settings and interact with consumers in novel ways to shape food choice. While studies suggest that all dimensions of the food environment influence diet and health outcomes, robust and consistent measurements of food environments that integrate objective and subjective components are essential for developing stronger evidence needed to shift public policies.