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BACKGROUND: Trauma can result in systemic inflammation that leads to organ dysfunction, but the impact on the brain, particularly following extracranial insults, has been largely overlooked. METHODS: Building upon our prior findings, we aimed to understand the impact of systemic inflammation on neuroinflammatory gene transcripts in eight brain regions in rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, 3 hours (h) of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4) BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 h post-injury (hpi). RESULTS: Globally, the number and magnitude of differentially expressed genes (DEGs) correlated with injury severity, systemic inflammation markers, and end-organ damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, and Tgfb2), neurosteroids/prostaglandins (Cyp19a1, Ptger2, and Ptger3), and markers of neurodegeneration (Gfap, Grin2b, and Homer1). Regional neuroinflammatory activity was least impacted following BOP. Non-blast trauma (in the BU and CEI+tI+HLA groups) contributed to an earlier, robust and diverse neuroinflammatory response across brain regions (up to 2-50-fold greater than that in the BOP group), while combined trauma (in the BOP+CEI+dHLA group) significantly advanced neuroinflammation in all regions except for the cerebellum. In contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated that the onset, extent, and duration of the inflammatory response are brain region dependent. Regardless of injury type, the thalamus and hypothalamus, which are critical for maintaining homeostasis, had the most DEGs. Our results indicate that neuroinflammation in all groups progressively increased or remained at peak levels over the study duration, while markers of end-organ dysfunction decreased or otherwise resolved. CONCLUSIONS: Collectively, these findings emphasize the brain's sensitivity to mediators of systemic inflammation and provide an example of immune-brain crosstalk. Follow-on molecular and behavioral investigations are warranted to understand the short- to long-term pathophysiological consequences on the brain, particularly the mechanism of blood-brain barrier breakdown, immune cell penetration-activation, and microglial activation.
Subject(s)
Brain , Inflammation , Neuroinflammatory Diseases , Animals , Rats , Brain/metabolism , Brain/pathology , Male , Inflammation/metabolism , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/etiology , Rats, Sprague-Dawley , Gene Expression , Gene Expression RegulationABSTRACT
Community-based policy, systems, and environmental interventions have the potential to reduce modifiable risk factors for obesity early in life. The purpose of this scoping review was to characterize the breadth, generalizability, and methodological quality of community-based diet and obesity-related policy, system, and environmental interventions during the first 1000 days of life, from pregnancy to 24 months of age. Eight databases were searched, and 83 studies (122 references) were included. Data were extracted for breadth (intervention characteristics), generalizability (reach, effectiveness, adoption, implementation, and maintenance), and study quality (Downs and Black Checklist). Systems and environmental approaches were common (> 80%), relative to policy approaches (39%). The majority (60-69%) occurred in the prenatal period and early infancy (0-3 months), assessed breastfeeding or child growth/obesity (53% for both), and included people with lower income (80%) or racial and/or ethnic minority groups (63%). Many interventions reported positive outcomes (i.e., in the expected direction) for child diet, breastfeeding, and feeding practices (> 62%). Few reported intervention maintenance or spanned the full 1000 days. Most studies were classified as good (32%) or fair (56%) methodological quality. The interventions mainly addressed pregnancy and early infancy. Rigorous and representative investigation is needed to improve intervention reach, sustainability, and application in toddlerhood.
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We numerically investigate the effect of an asymmetric periodic obstacle array in a two-dimensional active nematic. We find that activity in conjunction with the asymmetry leads to a ratchet effect or unidirectional flow of the fluid along the asymmetry direction. The directional flow is still present even in the active turbulent phase when the gap between obstacles is sufficiently small. We demonstrate that the dynamics of the topological defects transition from flow mirroring to smectic-like as the gap between obstacles is made smaller, and explain this transition in terms of the pinning of negative winding number defects between obstacles. This also leads to a nonmonotonic ratchet effect magnitude as a function of obstacle size, so that there is an optimal obstacle size for ratcheting at fixed activity.
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AIM: To conduct a pilot randomized trial of an intervention to improve adolescent question-asking and provider education during paediatric diabetes visits. METHODS: Adolescents aged 11 to 17 with type 1 diabetes and their parents were enrolled from two urban tertiary paediatric clinics. Adolescents were randomised to the intervention group or control group. Adolescent consultations were audio-recorded, their HbA1c level was recorded, and they completed surveys after three clinic appointments. The intervention group completed a question prompt list and watched a video on a tablet with their parents before meeting their doctor and completed a short evaluation after each visit. RESULTS: Six consultant endocrinologists and ninety-nine adolescents and their parents participated. The intervention increased adolescents' question asking and provider education in diabetes encounters. Total patient question-asking across the 3 consultations and a higher baseline HbA1c at time one was significantly associated with HbA1c at time three. CONCLUSIONS: Question prompt lists and an educational video are useful tools to increase adolescents' question-asking and communication between adolescents and their providers. PRACTICE IMPLICATIONS: Interventions that encourage adolescents' question-asking in healthcare encounters may lead to more meaningful providers-adolescents' communication and tailored education. Interventions to improve professionals' listening, communication and educational skills are also required.
Subject(s)
Communication , Diabetes Mellitus, Type 1 , Physician-Patient Relations , Humans , Adolescent , Male , Pilot Projects , Female , Diabetes Mellitus, Type 1/therapy , Child , Glycated Hemoglobin/analysis , Patient Education as Topic/methods , Parents/psychology , Surveys and QuestionnairesABSTRACT
Residual osteomyelitis is a frequent problem following surgical intervention for diabetic foot infection. The Infectious Disease Society of America guidelines recommend a prolonged course of antibiotics for treatment of residual osteomyelitis. Recent literature suggests oral antibiotic therapy is not inferior to IV therapy. The primary aim of this study was to evaluate treatment success in 128 patients receiving oral versus IV antibiotics for residual osteomyelitis in the diabetic foot after amputation at a Level 1 academic medical trauma center. Treatment success was defined as completion of at least 4 weeks of antibiotic therapy, complete surgical wound healing, and no residual infection requiring further debridement or amputation within 1 year of the initial surgery. Patients with peripheral arterial disease were excluded. A retrospective chart review was performed, and we found no statistically significant difference in treatment success between these two groups (p = .2766). The median time to healing for oral antibiotic treatment was 3.17 months compared to 4.06 months for IV treatment (p = .1045). Furthermore, there was no significant difference in group demographics or comorbidities, aside from more patients in the IV group having coronary artery disease (p = .0416). The type of closure and whether the infection was single or polymicrobial were also not associated with a difference in outcomes between the two treatment arms. The results of the present study suggest oral antibiotics for treatment of residual osteomyelitis are not inferior to IV therapy and may be more efficacious for certain patients regarding cost and ease of administration.
Subject(s)
Anti-Bacterial Agents , Diabetic Foot , Osteomyelitis , Trauma Centers , Humans , Osteomyelitis/drug therapy , Osteomyelitis/etiology , Osteomyelitis/microbiology , Male , Female , Retrospective Studies , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Middle Aged , Diabetic Foot/drug therapy , Diabetic Foot/microbiology , Administration, Oral , Aged , Administration, Intravenous , Academic Medical Centers , Treatment Outcome , Wound Healing/drug effects , Amputation, SurgicalABSTRACT
BACKGROUNDWhile the benefits of statin therapy on atherosclerotic cardiovascular disease are clear, patients often experience mild to moderate skeletal myopathic symptoms, the mechanism for which is unknown. This study investigated the potential effect of high-dose atorvastatin therapy on skeletal muscle mitochondrial function and whole-body aerobic capacity in humans.METHODSEight overweight (BMI, 31.9 ± 2.0) but otherwise healthy sedentary adults (4 females, 4 males) were studied before (day 0) and 14, 28, and 56 days after initiating atorvastatin (80 mg/d) therapy.RESULTSMaximal ADP-stimulated respiration, measured in permeabilized fiber bundles from muscle biopsies taken at each time point, declined gradually over the course of atorvastatin treatment, resulting in > 30% loss of skeletal muscle mitochondrial oxidative phosphorylation capacity by day 56. Indices of in vivo muscle oxidative capacity (via near-infrared spectroscopy) decreased by 23% to 45%. In whole muscle homogenates from day 0 biopsies, atorvastatin inhibited complex III activity at midmicromolar concentrations, whereas complex IV activity was inhibited at low nanomolar concentrations.CONCLUSIONThese findings demonstrate that high-dose atorvastatin treatment elicits a striking progressive decline in skeletal muscle mitochondrial respiratory capacity, highlighting the need for longer-term dose-response studies in different patient populations to thoroughly define the effect of statin therapy on skeletal muscle health.FUNDINGNIH R01 AR071263.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscular Diseases , Male , Adult , Female , Humans , Atorvastatin/pharmacology , Atorvastatin/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Mitochondria , Muscular Diseases/metabolismABSTRACT
We numerically model a two-dimensional active nematic confined by a periodic array of fixed obstacles. Even in the passive nematic, the appearance of topological defects is unavoidable due to planar anchoring by the obstacle surfaces. We show that a vortex lattice state emerges as activity is increased, and that this lattice may be tuned from "ferromagnetic" to "antiferromagnetic" by varying the gap size between obstacles. We map the rich variety of states exhibited by the system as a function of distance between obstacles and activity, including a pinned defect state, motile defects, the vortex lattice, and active turbulence. We demonstrate that the flows in the active turbulent phase can be tuned by the presence of obstacles, and explore the effects of a frustrated lattice geometry on the vortex lattice phase.
ABSTRACT
Low back pain due to spaceflight is a common complaint of returning astronauts. Alterations in musculoskeletal anatomy during spaceflight and the effects of microgravity (µg) have been well-studied; however, the mechanisms behind these changes remain unclear. The National Aeronautics and Space Administration has released the Human Research Roadmap to guide investigators in developing effective countermeasure strategies for the Artemis Program, as well as commercial low-orbit spaceflight. Based on the Human Research Roadmap, the existing literature was examined to determine the current understanding of the effects of microgravity on the musculoskeletal components of the spinal column. In addition, countermeasure strategies will be required to mitigate these effects for long-duration spaceflight. Current pharmacologic and nonpharmacologic countermeasure strategies are suboptimal, as evidenced by continued muscle and bone loss, alterations in muscle phenotype, and bone metabolism. However, studies incorporating the use of ultrasound, beta-blockers, and other pharmacologic agents have shown some promise. Understanding these mechanisms will not only benefit space technology but likely lead to a return on investment for the management of Earth-bound diseases.
Subject(s)
Low Back Pain , Space Flight , Weightlessness , Humans , Astronauts , Spine , Weightlessness/adverse effectsABSTRACT
PURPOSE: This paper aims to examine the association between asthma severity and one-year lagged fitness in New York City Public school youth by neighborhood opportunity. METHODS: Using the Child Opportunity Index 2.0 and individual-level repeated measures NYC Office of School Health (OSH) fitness surveillance data (2010-2018), we ran multilevel mixed models stratified by neighborhood opportunity, adjusting for sex, race/ethnicity, grade level, poverty status, and time. Asthma severity was based on a physician-completed Asthma Medication Administration Form (MAF) from each school year and drawn from the Automated Student Health Record (ASHR). RESULTS: Across all youth in grades 4-12 (n = 939,598; 51.7 % male; 29.9 % non-Hispanic Black, 39.3 % Hispanic; 70.0 % high poverty), lower neighborhood opportunity was associated with lower subsequent fitness. Youth with severe asthma and very low and low neighborhood opportunity had the lowest 1-year lagged fitness z-scores - 0.24 (95 % CI, -0.34 to -0.14) and - 0.26 (95 % CI, -0.32 to -0.20), respectively, relative to youth with no asthma and very high opportunity. CONCLUSIONS: An inverse longitudinal relationship between asthma severity and subsequent fitness was observed. Study findings have implications for public health practitioners to promote physical activity and improved health equity for youth with asthma, taking neighborhood factors into account.
Subject(s)
Asthma , Physical Fitness , Child , Humans , Male , Adolescent , Female , New York City/epidemiology , Exercise , Poverty , Residence Characteristics , Asthma/epidemiologyABSTRACT
Conventional type 1 dendritic cells (DC1) contribute to the development of pathogenic T helper type 1 (Th1) cells in part via the production of the proinflammatory cytokine interleukin-12. Thus, depletion of DC1 has the potential to dampen autoimmune responses. Here, we developed X-C motif chemokine receptor 1 (XCR1)-specific chimeric antigen receptor (CAR)-T cells and CAR-Tregs that specifically targeted DC1. XCR1 CAR-T cells were successfully generated as CD4+ and CD8+ T cells, expressed XCR1 CAR efficiently, and induced XCR1-dependent activation, cytokine production and proliferation. XCR1 CAR-T cells selectively depleted DC1 when transferred into RAG2-/- mice with a compensatory increase in conventional type 2 DC (DC2) and plasmacytoid DC (pDC). XCR1 CAR-T cell-mediated depletion of DC1 modestly suppressed the onset of Th1-driven experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Diphtheria toxin-mediated DC1 depletion in XCR1-diphtheria toxin receptor mice also suppressed EAE, suggesting that DC1 depletion was responsible for EAE suppression. XCR1 CAR-Tregs were successfully generated and suppressed effector T cells in the presence of XCR1+ cells. Therapeutic treatment with XCR1 CAR-Tregs suppressed Th1-driven EAE. Therefore, we conclude that depletion of DC1 with XCR1 CAR-T cells or immune suppression with XCR1 CAR-Tregs can modestly suppress Th1-driven EAE.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Mice , Animals , CD8-Positive T-Lymphocytes/pathology , Cytokines/metabolism , Th1 Cells , Dendritic CellsABSTRACT
Background: Fewer than 1/4th of US children and adolescents meet physical activity (PA) guidelines, leading to health disparities that track into adulthood. Neighborhood opportunity may serve as a critical modifiable factor to improve fitness attainment and reduce these disparities. We drew data from the Child Opportunity Index to examine associations between neighborhood indicators of opportunity for PA and multiple fitness indicators among New York City public school youth. Methods: Multilevel generalized linear mixed models were used to estimate the overall and sex-stratified associations between neighborhood indicators (green space, healthy food, walkability, commute time) and indicators for physical fitness [curl-ups, push-ups, Progressive Aerobic Cardiovascular Endurance Run (PACER), sit-and-reach] using the New York City FITNESSGRAM data set. Results: The analytic sample [n = 299,839; median (interquartile range) age = 16 (12-17)] was 50.1% female, 37.5% Hispanic, 26.2% non-Hispanic Black, and most (69.5%) qualified for free/reduced price school meals. Neighborhood indicators were positively associated with higher values of indicators for physical fitness. The strongest associations were observed between walkability and both BMI and PACER, and commute time with BMI, push-ups, and PACER. For example, walkability had the greatest magnitude of effects for BMI and muscular strength and endurance (BMI: ß: -0.75, 95% confidence interval, CI: -1.01 to -0.49; PACER: ß: 1.98, 95% CI: 1.59 to 2.37), and particularly for girls compared with boys (BMI, girls: ß: -0.91, 95% CI: -1.22 to -0.66); BMI, boys: ß: -0.56, 95% CI: -0.86 to -0.25); PACER, girls: ß: 2.11, 95% CI: 1.68 to 2.54; push-ups, boys: ß: 1.71, 95% CI: 1.31 to 2.12). Conclusion: Neighborhood indicators were associated with multiple measures of youth fitness. Continued research on neighborhood opportunity and youth fitness may better inform place-based public health interventions to reduce disparities.
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BACKGROUND: Neighbourhood factors are associated with cardiovascular health in adults, but these relationships are under-explored in youth. OBJECTIVES: To characterize the associations between neighbourhood factors and child and adolescent health among youth with obesity. METHODS: Data were drawn from patient health records at a pediatric weight management clinic (n = 2838) and the Child Opportunity Index (COI). Exposures were area-level neighbourhood factors (commute duration, walkability, greenspace and industrial pollutants). Outcomes included BMI relative to the 95th percentile (BMIp95) and blood pressure (continuous variables). Longitudinal models examined associations between COI indicators and outcomes. RESULTS: Shorter commute duration (ß = -4.31, 95% CI: -5.92, -2.71) and greater walkability (ß = -4.40, 95% CI: -5.98, -2.82) were negatively associated with BMIp95. Increased greenspace availability was positively associated with BMIp95 (ß = 1.93, 95% CI: 0.19, 3.67). None of the COI indicators were associated with cardiovascular outcomes in the full sample. Analyses stratified by sex and race/ethnicity showed similar patterns for BMIp95. For commute duration, there was a negative association with blood pressure for female, non-Hispanic White and other race/ethnicity youth. CONCLUSIONS: Neighbourhood factors should be considered as contextual factors when treating youth with obesity. Additional research is needed to understand the relationship between neighbourhood factors and cardiovascular outcomes.
Subject(s)
Cardiovascular Diseases , Adult , Child , Humans , Female , Adolescent , Cardiovascular Diseases/epidemiology , Risk Factors , Obesity/epidemiology , Obesity/therapy , Blood Pressure , Heart Disease Risk Factors , Residence CharacteristicsABSTRACT
Using a minimal continuum model, we investigate the interplay between circular confinement and substrate friction in active nematics. Upon increasing the friction from low to high, we observe a dynamical phase transition from a circulating flow phase to an anisotropic flow phase in which the flow tends to align perpendicular to the nematic director at the boundary. We demonstrate that both the flow structure and dynamic correlations in the latter phase differ from those of an unconfined, active turbulent system and may be controlled by the prescribed nematic boundary conditions. Our results show that substrate friction and geometric confinement act as valuable control parameters in active nematics.
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Background: Prior investigators have examined the relationship between neighborhood public transportation access and physical activity among adolescents, but research is lacking on the association with obesity in this age group. This study examines the association between neighborhood public transportation access and adolescent BMI using a national sample. Methods: We used cross-sectional data from the Family Life, Activity, Sun, Health, and Eating study, a national survey (2014) that assessed physical activity and diet, among adolescents (aged 12-17 years, N = 1737) and their parents. We ran crude and adjusted linear regression models to test the association between neighborhood-level public transportation access (less prevalent and prevalent) and individual participant-level BMI z-scores. Results: The analytic sample included 336 adolescents (50% female; 69% had healthy weight; 28% had overweight or obesity). Adjusted models showed a positive relationship between high public transportation access and adolescent z-BMI (b = 0.25, confidence interval [95% CI]: -0.01 to 0.50). In stratified analyses, high public transportation access was associated with higher z-BMI for high school students (b = 0.57, 95% CI: 0.23-0.91), males (b = 0.48, 95% CI: 0.09-0.87), and adolescents in households with an income below $99,999 (0.29, 95% CI: 0.02-0.56). Conclusion: Neighborhood public transportation access is associated with adolescent BMI, but the direction of this association varies across urban adolescent demographic subgroups. Further research is needed to clarify the relationships between individual and social-environmental factors that impact public transportation access and its association with adolescent BMI.
ABSTRACT
Neighborhood environments can support fitness-promoting behavior, yet little is known about their influence on youth physical fitness outcomes over time. We examined longitudinal associations between neighborhood opportunity and youth physical fitness among New York City (NYC) public school youth. The Child Opportunity Index (COI), a composite index of 29 indicators measuring neighborhood opportunity at the census-tract level, along with scores on 4 selected COI indicators were linked to NYC FITNESSGRAM youth data at baseline. Fitness outcomes (measured annually, 2011-2018) included body mass index, curl-ups, push-ups, and Progressive Aerobic Cardiovascular Endurance Run (PACER) laps. Unstratified and age-stratified, adjusted, 3-level generalized linear mixed models, nested by census tract and time, estimated the association between COI and fitness outcomes. The analytical sample (n = 204,939) lived in very low (41%) or low (30%) opportunity neighborhoods. Unstratified models indicated that overall COI is modestly associated with improved youth physical fitness outcomes. The strongest opportunity-fitness associations were observed for PACER. Stratified models show differences in associations across younger vs. older youth. We find that neighborhood factors are associated with youth fitness outcomes over time, with the strength of the associations dependent on age. Future implications include better informed place-based interventions tailored to specific life stages to promote youth health.
Subject(s)
Exercise , Physical Fitness , Humans , Child , Adolescent , New York City , Body Mass Index , SchoolsABSTRACT
Severe persistent childhood asthma is associated with low physical activity and may be associated with poor physical fitness. Research on the asthma severity-fitness association longitudinally and across sociodemographic subgroups is needed to inform fitness interventions targeting youth with asthma. We evaluated the relationship between asthma severity (categorized as severe, mild, or no asthma) and subsequent fitness in New York City (NYC) public school youth enrolled in grades 4-12 using the NYC Fitnessgram dataset (2010-2018). Longitudinal mixed models with random intercepts were fit to test the association between asthma severity and one-year lagged fitness z-scores by clustering repeated annual observations at the student level. Models were adjusted for sex, race/ethnicity, grade level, poverty status, time, and stratified by sociodemographic factors. The analytic sample included 663,137 students (51% male; 31% non-Hispanic Black, 40% Hispanic; 55% in grades 4-8, 70% high poverty; 87%, 11% and 1% with no, mild, and severe asthma, respectively). Students with severe asthma and mild asthma demonstrated -0.19 (95% CI, -0.20 to -0.17) and - 0.10 (95% CI, -0.11 to -0.10), respectively, lower fitness z-scores in the subsequent year relative to students without asthma. After stratifying by demographics, the magnitude of the asthma severity-fitness relationship was highest for non-Hispanic white vs. all other racial/ethnic subgroups, and was similar across sex, grade level, and household poverty status. Overall, we observed an inverse longitudinal relationship between asthma severity and subsequent fitness among urban youth, particularly non-Hispanic Whites. Future research should examine how neighborhood-level factors impact the asthma severity-fitness relationship across racial/ethnic subgroups.
Subject(s)
Asthma , Physical Fitness , Humans , Male , Adolescent , Child , Female , New York City/epidemiology , Exercise , Students , SchoolsABSTRACT
BACKGROUND: Obesity is associated with poorer youth fitness. However, little research has examined the magnitude of this relationship in youth with severe obesity. Therefore, we sought to determine the relationship between increasing weight status and fitness within a sample of children and adolescents from New York City public schools. METHODS: This study utilized longitudinal data from the NYC Fitnessgram dataset years 2010-2018. Height and weight along with fitness were measured annually during physical education classes. Severity of obesity was defined using body mass index relative to the 95th percentile and then categorized into classes. A composite measure of fitness was calculated based on scores for three fitness tests: aerobic capacity, muscular strength, and muscular endurance. To examine the weight status-fitness relationship, repeated measures mixed models with random-intercepts were constructed. Stratified models examined differences by demographic factors. RESULTS: The sample included 917,554 youth (51.8% male, 39.3% Hispanic, 29.9% non-Hispanic Black, 14.0%, 4.6%, and 1.6% class I, II and III obesity, respectively). Compared to youth with healthy weight, increasing severity of obesity was associated with decreased fitness: overweight (ß = - 0.28, 95% CI:-0.29;-0.28), class I obesity (ß = - 0.60, 95% CI:-0.60; - 0.60), class II obesity (ß = - 0.94, 95% CI:-0.94; - 0.93), and class III obesity (ß = - 1.28; 95% CI:-1.28; - 1.27). Stratified models showed the association was stronger among male and non-Hispanic White youth. CONCLUSION: Findings revealed that more severe obesity was associated with lower fitness. Future research is needed to develop targeted interventions to improve fitness in youth with obesity.
Subject(s)
Obesity, Morbid , Child , Humans , Male , Adolescent , Female , Physical Fitness , New York City/epidemiology , Obesity/epidemiology , Body Mass Index , SchoolsABSTRACT
BACKGROUND: Safe and effective treatment exists for childhood obesity, but treatment recommendations have largely not been translated into practice, particularly among racial and ethnic minorities and low-wealth populations. A key gap is meeting the recommended treatment of ≥26 h of lifestyle modification over 6-12 months. Fit Together is an effective treatment model that meets these recommendations by integrating healthcare and community resources. Pediatric providers screen children for obesity, deliver counseling, and treat co-morbidities, while Parks and Recreation partners provide recreation space for a community nutrition and physical activity program. METHODS: This study will use a hybrid type II implementation-effectiveness design to evaluate the effectiveness of an online implementation platform (the Playbook) for delivering Fit Together. Clinical and community partners in two North Carolina communities will implement Fit Together, using the Playbook, an implementation package designed to facilitate new partnerships, guide training activities, and provide curricular materials needed to implement Fit Together. An interrupted time series design anchored in the Process Redesign Framework will be used to evaluate implementation and effectiveness outcomes in intervention sites. Implementation measures include semi-structured interviews with partners, before and after the implementation of Fit Together, and quantitative measures assessing several constructs within the Process Redesign Framework. The participants will be children 6-11 years old with obesity and their families (n=400). Effectiveness outcomes include a change in child body mass index and physical activity from baseline to 6 and 12 months, as compared with children receiving usual care. Findings will be used to inform the design of a dissemination strategy guided by the PCORI Dissemination Framework. DISCUSSION: This project addresses the knowledge-to-action gap by developing evidence-based implementation tools that allow clinicians and communities to deliver effective pediatric obesity treatment recommendations. Future dissemination of these tools will allow more children who have obesity and their families to have access to effective, evidence-based care in diverse communities. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05455190 . Registered on 13 July 2022.